ORCID Profile
0000-0002-8443-314X
Current Organisations
Burnet Institute
,
Royal Melbourne Hospital
,
Peter MacCallum Cancer Centre
,
University of Melbourne
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Publisher: Elsevier BV
Date: 2020
Publisher: Informa UK Limited
Date: 23-07-2019
Publisher: Springer Science and Business Media LLC
Date: 22-05-2023
DOI: 10.1007/S40279-023-01862-9
Abstract: Cancer-related pain is common and undertreated. Exercise is known to have a pain-relieving effect in non-cancer pain. This systematic review aimed to evaluate (1) the effect of exercise on cancer-related pain in all cancers, and (2) whether the effect of exercise differed according to exercise mode, degree of supervision, intervention duration and timing (during or after cancer treatment), pain types, measurement tool and cancer type. Electronic searches were undertaken in six databases to identify exercise studies evaluating pain in people with cancer, published prior to 11 January 2023. All stages of screening and data extraction were conducted independently by two authors. The Cochrane risk of bias tool for randomised trials (RoB 2) was used and overall strength of evidence was assessed using the GRADE approach. Meta-analyses were performed overall and by study design, exercise intervention and pain characteristics. In total, 71 studies reported in 74 papers were eligible for inclusion. The overall meta-analysis included 5877 participants and showed reductions in pain favouring exercise (standardised mean difference − 0.45 95% confidence interval − 0.62, − 0.28). For most ( 82%) of the subgroup analyses, the direction of effect favoured exercise compared with usual care, with effect sizes ranging from small to large (median effect size − 0.35 range − 0.03 to − 1.17). The overall strength of evidence for the effect of exercise on cancer-related pain was very low. The findings provide support that exercise participation does not worsen cancer-related pain and that it may be beneficial. Better pain categorisation and inclusion of more erse cancer populations in future research would improve understanding of the extent of benefit and to whom. CRD42021266826.
Publisher: Wiley
Date: 17-09-2020
DOI: 10.1111/MYC.13178
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 02-2008
Publisher: Informa UK Limited
Date: 16-03-2012
Publisher: Wiley
Date: 06-2008
DOI: 10.1111/J.1445-5994.2008.01723.X
Abstract: Antifungal prophylaxis can be recommended in patients undergoing induction chemotherapy for acute myeloid leukemia and treatment for grade 2 or greater or chronic extensive graft versus host disease. The evidence for prophylaxis is less clear in other clinical settings although certain groups such as patients with prolonged neutropenia after stem cell transplants using bone marrow or cord blood sources and with impaired cell mediated immunity secondary to treatments such as Alemtuzumab are at high risk. The decision to use prophylaxis and which agent to use will be influenced by effectiveness, number needed to treat and the likelihood of toxicity and drug interactions. The availability of rapid diagnostic tests for fungal infection and institutional epidemiology will also influence the need for and choice of prophylaxis. Whilst prophylaxis can be beneficial, it may impede the ability to make a rapid diagnosis of fungal infection by reducing the yield of diagnostic tests and change the epidemiology of fungal infection. As non-culture based diagnostic tests are refined and become more available there may be a shift from prophylaxis to early diagnosis and treatment.
Publisher: Hindawi Limited
Date: 25-08-2011
DOI: 10.1111/J.1365-2354.2011.01282.X
Abstract: A number of treatments for breast cancer induce menopause. This study's aim was to explore women's perceptions and beliefs about menopausal symptoms and their management following breast cancer, and to compare younger and older women's experiences. Data were collected via semi-structured focus groups from women who had undergone treatment for breast cancer, and who were currently experiencing menopausal symptoms. Data were interpreted by way of simple inductive thematic analysis. The women experienced a range of menopausal symptoms that they were not prepared for and found difficult to manage. The central themes related to their lack of knowledge of how to manage menopausal symptoms, and the distress and helplessness that arose from this. Women who were diagnosed prior to 40 years of age reported additional menopausal issues than women who were older at diagnosis. The women in this study expressed a thirst for information related to menopause after breast cancer. The women identified that their needs with regard to menopause after breast cancer were not being met, either through their own lack of knowledge or via conflicting or absent support and management. The importance of enabling women to deal with menopausal symptoms was a central theme to emerge from the data.
Publisher: Elsevier BV
Date: 12-2003
DOI: 10.1111/J.1469-0691.2003.00762.X
Abstract: Esophageal perforation due to Candida glabrata is a rare entity. This organism is uncommonly recognized to be angio-invasive and cause gastrointestinal tract perforation. Herein, we describe a case of invasive C. glabrata infection leading to esophageal perforation in a patient undergoing hemopoietic stem cell transplantation.
Publisher: Informa UK Limited
Date: 11-01-2019
Publisher: Springer Science and Business Media LLC
Date: 15-04-2020
Publisher: Oxford University Press (OUP)
Date: 13-03-2013
DOI: 10.1093/JAC/DKT068
Abstract: Fluconazole, posaconazole and voriconazole are used prophylactically in patients with acute myeloid leukaemia (AML). This study evaluated the clinical and economic outcomes of these agents when used in AML patients undergoing consolidation chemotherapy. A retrospective chart review (2003-10) of AML patients receiving consolidation chemotherapy was performed. Patients were followed through their first cycle of consolidation chemotherapy. Antifungal prescribing patterns, clinical outcomes and resource consumptions were recorded. A decision analytical model was developed to depict the downstream consequences of using each antifungal agent, with success defined as completion of the designated course of initial antifungal prophylaxis without developing invasive fungal disease (IFD). Cost-effectiveness and sensitivity analyses were performed. A total of 106 consecutive patients were analysed. Baseline characteristics and predisposing factors for IFD were comparable between groups. Three IFDs (one proven, one probable and one suspected) occurred, all in the posaconazole group. Patients receiving posaconazole had the highest rate of intolerance requiring drug cessation (13% versus 7% in each of the fluconazole and voriconazole groups). Fluconazole conferred overall savings per patient of 26% over posaconazole and 13% over voriconazole. Monte Carlo simulation demonstrated a mean cost saving with fluconazole of AU$8430 per patient (95% CI AU$5803-AU$11 054) versus posaconazole and AU$3681 per patient (95% CI AU$990-AU$6319) versus voriconazole. One-way sensitivity analyses confirmed the robustness of the model. This is the first study to show that, in the setting of consolidation therapy for AML, fluconazole is the most cost-effective approach to antifungal prophylaxis compared with posaconazole or voriconazole.
Publisher: Oxford University Press (OUP)
Date: 25-06-2015
DOI: 10.1093/CID/CIV507
Publisher: Elsevier BV
Date: 06-2015
DOI: 10.1016/J.CLINTHERA.2015.03.021
Abstract: Patients with persistent or recurrent neutropenic fevers at risk of invasive fungal disease (IFD) are treated empirically with antifungal therapy (AFT). Early treatment using a diagnostic-driven (DD) strategy may reduce clinical and economic burdens. We compared costs and outcomes of both strategies from a UK perspective. An empirical strategy with conventional hotericin B deoxycholate (C-AmB), liposomal hotericin B (L-AmB), or caspofungin was compared with a DD strategy (initiated based on positive ELISA results for galactomannan antigen) and/or positive results for Aspergillus species on polymerase chain reaction assay) using C-AmB, voriconazole, or L-AmB in a decision-analytic model. Rates of IFD incidence, overall mortality, and IFD-related mortality in adults expected to be neutropenic for ≥10 days were obtained. The empirical strategy was assumed to identify 30% of IFD and targeted AFT to improve survival by a hazard ratio of 0.589. AFT-specific adverse events were obtained from a summary of product characteristics. Resource use was obtained, and costs were estimated by using standard UK costing sources. All costs are presented in 2012 British pounds sterling. Total costs were 32% lower for the DD strategy (£1561.29) versus the empirical strategy (£2301.93) due to a reduced incidence of adverse events and decreased use of AFT. Administration of AFT was reduced by 41% (DD strategy, 74 of 1000 empirical strategy, 125 of 1000), with similar survival rates. This study suggests that a DD strategy is likely to be cost-saving versus empirical treatment for immunocompromised patients with persistent or recurrent neutropenic fevers.
Publisher: Wiley
Date: 20-10-2023
DOI: 10.1111/TID.14171
Publisher: Wiley
Date: 2009
DOI: 10.1111/J.1445-5994.2008.01867.X
Abstract: In immunocompromised patients, endovascular infection due to Candida albicans is associated with significant morbidity and mortality. Recommended management includes removal of any existing central venous catheter. Rarely, complications of endocarditis or infected mural thrombi may arise, with poorer clinical outcomes. For large endoluminal lesions, particularly of the great vessels or those that are intra-atrial, thrombolysis has been used in paediatric populations or before surgery for dissolution of infected thrombus. We describe the case of an adult patient with lung carcinoma who developed persisting candidaemia with a large endovascular fungal lesion adherent to the tip of a peripherally inserted central venous catheter. Local urokinase infusion enabled safe removal of the catheter without embolization. As an adjunct to antifungal therapy, local thrombolysis may play a contributory role in the management of central venous catheter-related candidal septic thrombosis.
Publisher: Elsevier BV
Date: 03-2021
Publisher: Frontiers Media SA
Date: 05-10-2017
Publisher: Springer Science and Business Media LLC
Date: 08-07-2017
Publisher: Wiley
Date: 16-03-2023
DOI: 10.1111/TID.14049
Abstract: Liver transplantation is increasing worldwide with underlying pathologies dominated by metabolic and alcoholic diseases in developed countries. We provide a narrative review of invasive aspergillosis (IA) in liver transplant (LT) recipients. We searched PubMed and Google Scholar for references without language and time restrictions. The incidence of IA in LT recipients is low (1.8%), while mortality is high (∼50%). It occurs mainly early ( months) after LT. Some risk factors have been identified before (corticosteroid, renal, and liver failure), during (massive transfusion and duration of surgical procedure), and after transplantation (intensive care unit stay, re‐transplantation, re‐operation). Diagnosis can be difficult and therefore requires full radiological and clinicobiological collaboration. Accurate identification of Aspergillus species is recommended due to the cryptic species, and susceptibility testing is crucial given the increasing resistance of Aspergillus fumigatus to azoles. It is recommended to reduce the dose of tacrolimus (50%) and to closely monitor the trough level when introducing voriconazole, isavuconazole, and posaconazole. Surgery should be discussed on a case‐by‐case basis. Antifungal prophylaxis is recommended in high‐risk patients. Environmental preventative measures should be implemented to prevent outbreaks of nosocomial aspergillosis in LT recipient units. IA remains a very serious disease in LT patients and should be promptly sought and, if possible, prevented by clinicians when risk factors are identified. image
Publisher: Wiley
Date: 24-04-2014
DOI: 10.1111/MYC.12199
Abstract: We report a case of non-fatal disseminated Scedosporium prolificans infection, including central nervous system disease and endophthalmitis, in a relapsed acute myeloid leukaemia patient with extensive CYP2C19 metabolism. Successful treatment required aggressive surgical debridement, three times daily voriconazole dosing and cimetidine CYP2C19 inhibition. In addition, the unique use of miltefosine was employed due to azole-chemotherapeutic drug interactions. Prolonged survival following disseminated S. prolificans, adjunctive miltefosine and augmentation of voriconazole exposure with cimetidine CYP2C19 inhibition has not been reported.
Publisher: Cambridge University Press (CUP)
Date: 04-2008
DOI: 10.1086/528879
Abstract: We evaluated 66 patients in a hematology unit, who used a total of 106 central venous catheters (CVCs), to identify CVC-associated bloodstream infections using standard and modified surveillance case definitions. Compared with the National Nosocomial Infection Surveillance system criteria, a modified case definition used by treating physicians demonstrated 100.0% sensitivity and 94.3% specificity. This case definition provides a practical method for effectively excluding CVC-associated bloodstream infection.
Publisher: Elsevier BV
Date: 09-2023
Publisher: Oxford University Press (OUP)
Date: 18-05-2017
DOI: 10.1093/CID/CIX244
Abstract: An integrated antibiotic allergy testing program resulted in increased prescribing of narrow-spectrum β-lactams and reduction in restricted antibiotics and inappropriate prescriptions. The program effectively and safely de-labeled patients, with % of antibiotic allergy labels removed following testing.
Publisher: Elsevier BV
Date: 03-2004
DOI: 10.1016/J.IJID.2003.05.001
Abstract: This study examined the burden of hospitalization of patients with Aspergillus and Candida infections in Australia from 1995 to 1999. Data were extracted from the National Hospital Morbidity Database. A hospitalization with an aspergillosis diagnosis was defined as any discharge with a diagnosis of aspergillosis. A hospitalization with a candidiasis diagnosis was defined as any discharge with a diagnosis of disseminated, invasive, or non-invasive candidiasis. Outcome measures included number of hospitalizations, length of stay (LOS), cost (AUS$), and mortality. 4583 hospitalizations with an aspergillosis diagnosis and 57,758 hospitalizations with a candidiasis diagnosis were identified. These hospitalizations were associated with a total of 813,398 hospital days, AUS$563 million in cost, and 4967 in-hospital deaths during the study period. The mean LOS for a hospitalization with an aspergillosis diagnosis was 12 days, cost AUS$9,334, and was associated with 8% mortality. For disseminated, invasive, and non-invasive candidiasis, the respective mean LOS were 31, 17, and 12 days costs were AUS$33,274, AUS$12,954, and AUS$7,694 and mortality was 26%, 9%, and 8%. Hospitalizations with diagnoses for fungal infections were associated with lengthy hospital stays, high costs, and high mortality.
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 10-2006
Abstract: Population-based surveillance for candidemia in Australia from 2001 to 2004 identified 1,095 cases. Annual overall and hospital-specific incidences were 1.81/100,000 and 0.21/1,000 separations (completed admissions), respectively. Predisposing factors included malignancy (32.1%), indwelling vascular catheters (72.6%), use of antimicrobial agents (77%), and surgery (37.1%). Of 919 episodes, 81.5% were inpatient healthcare associated (IHCA), 11.6% were outpatient healthcare associated (OHCA), and 6.9% were community acquired (CA). Concomitant illnesses and risk factors were similar in IHCA and OHCA candidemia. IHCA candidemia was associated with sepsis at diagnosis (p<0.001), death <30 days after infection (p<0.001), and prolonged hospital admission (p or =65 years of age. Adult critical care stay, sepsis syndrome, and corticosteroid therapy were associated with the greatest risk for death. Systematic epidemiologic studies that use standardized definitions for IHCA, OHCA, and CA candidemia are indicated.
Publisher: Wiley
Date: 26-02-2007
DOI: 10.1002/CNCR.22527
Abstract: Central venous catheters are essential in the management of many malignant disorders, but catheter-related bloodstream infections (CR-BSIs) are significant complications in terms of morbidity, mortality, and healthcare expenditure. These outcome measures are useful for monitoring of infection control practice and the effect of preventive strategies. Unlike intensive care unit (ICU) populations, surveillance for CR-BSIs in the hematology population is not standardized, despite the potential value of detecting changes in rate, etiology, and changes in risk for infective complications in association with increasingly intensive chemotherapeutic regimens in this immunocompromised population. Essential components of a successful surveillance strategy include selection of a health outcome of significance, definition of goals of the surveillance system, involvement of key stakeholders in planning and development, application of valid case definitions, allocation of resources and trained personnel, risk stratification, and use of appropriate statistical methods for analysis. These are discussed with reference to patients with hematologic malignancy, together with review of previous surveillance strategies in this population. Only when these issues are addressed can a surveillance strategy reliably assess trends and compare data, leading to improved patient outcomes and a reduction in healthcare expenditure for patients with hematologic malignancy.
Publisher: Informa UK Limited
Date: 02-06-2017
Publisher: Wiley
Date: 18-03-2013
DOI: 10.1111/MYC.12071
Abstract: Micafungin was non-inferior to liposomal hotericin B (LAmB) for the treatment of candidaemia and invasive candidiasis (IC) in a major clinical trial. The present study investigated the economic impact of micafungin vs. LAmB in treating candidaemia and IC. A decision analytical model was constructed to capture downstream consequences of using micafungin or LAmB as primary definitive therapy. The main outcomes were treatment success and treatment failure due to mycological persistence, or death. Outcome probabilities were derived from key published sources. Resource used was estimated by an expert panel and cost inputs were from the latest Australian resources. The analysis was from an Australian hospital perspective. Sensitivity analyses using Monte Carlo simulation were conducted. Micafungin (AU$61 426) had a lower total cost than LAmB (AU$72 382), with a total net cost-saving of AU$10 957 per patient. This was primarily due to the lower cost associated with initial antifungal treatment and shorter length of stay for patients in the micafungin arm. Hospitalisation was the main cost driver for both arms. Results were robust over a wide range of variables. The uncertainty analysis demonstrated that micafungin had a 99.9% chance of being cost-saving compared with LAmB. Micafungin was associated with cost-saving relative to LAmB in the treatment of candidaemia and IC in Australia.
Publisher: Springer Science and Business Media LLC
Date: 30-05-2008
DOI: 10.1007/S11046-008-9131-2
Abstract: A man with acute lymphoblastic leukaemia developed disseminated Scedosporium prolificans infection following chemotherapy for disease relapse while on posaconazole prophylaxis. Scedosporium prolificans infection during posaconazole prophylaxis has not been reported previously. This report is timely as the uptake of posaconazole, the broadest spectrum azole clinically available, is likely to grow with recent evidence supporting its role as prophylaxis against invasive fungal infections in high-risk haematology patients.
Publisher: Oxford University Press (OUP)
Date: 11-08-2016
DOI: 10.1093/JAC/DKW322
Abstract: This study describes the safety, clinical effectiveness and trough plasma concentration (C A multicentre, retrospective study on the NPP use of iv posaconazole between July 2014 and March 2015 across seven Australian hospitals. Seventy courses of iv posaconazole were prescribed and evaluated in 61 patients receiving treatment for haematological malignancy. Sixty-one courses were prescribed for prophylaxis against invasive fungal disease (IFD), the majority of which (59) were initiated in patients with gastrointestinal disturbances and/or intolerance to previous antifungals. The median (IQR) duration for prophylaxis was 10 (6-15) days. No breakthrough IFD was observed during or at cessation of iv posaconazole. Nine courses of iv posaconazole were prescribed for treatment of IFD with a median (IQR) duration of 19 (7-30) days. Improvement in signs and symptoms of IFD was observed in five cases at cessation of, and six cases at 30 days post-iv posaconazole. C This non-clinical trial experience suggests that iv posaconazole appeared to be safe and clinically effective for prophylaxis or treatment of IFD in patients receiving treatment for haematological malignancies.
Publisher: Springer Science and Business Media LLC
Date: 15-05-2012
DOI: 10.1007/S00259-012-2143-7
Abstract: Febrile neutropenia (FNP) is a frequent complication of cancer care and evaluation often fails to identify a cause. [(18) F]FDG PET/CT has the potential to identify inflammatory and infectious foci, but its potential role as an investigation for persistent FNP has not previously been explored. The aim of this study was to prospectively evaluate the clinical utility of FDG PET/CT in patients with cancer and severe neutropenia and five or more days of persistent fever despite antibiotic therapy. Adult patients with a diagnosis of an underlying malignancy and persistent FNP (temperature ≥38°C and neutrophil count <500 cells/μl for 5 days) underwent FDG PET/CT as an adjunct to conventional evaluation and management. The study group comprised 20 patients with FNP who fulfilled the eligibility criteria and underwent FDG PET/CT in addition to conventional evaluation. The median neutrophil count on the day of the FDG PET/CT scan was 30 cells/μl (range 0-730 cells/μl). Conventional evaluation identified 14 distinct sites of infection, 13 (93 %) of which were also identified by FDG PET/CT, including all deep tissue infections. FDG PET/CT identified 9 additional likely infection sites, 8 of which were subsequently confirmed as "true positives" by further investigations. FDG PET/CT was deemed to be of 'high' clinical impact in 15 of the 20 patients (75 %). This study supports the utility of FDG PET/CT scanning in severely neutropenic patients with five or more days of fever. Further evaluation of the contribution of FDG PET/CT in the management of FNP across a range of underlying malignancies is required.
Publisher: Wiley
Date: 10-10-2020
DOI: 10.1111/JHN.12811
Abstract: Cancer cachexia (CC) is a multifactorial syndrome characterised by ongoing skeletal muscle loss that leads to progressive functional impairment driven by reduced food intake and abnormal metabolism. Despite the traditional use of non-volitional weight loss as the primary marker of CC, there is no consensus on how to diagnose and manage CC. The aim of this narrative review was to describe and discuss diagnostic criteria and therapeutic approaches for the accredited practicing dietitian with respect to identifying and managing CC. Available diagnostic criteria for cachexia include the cancer-specific (Fearon and Cachexia Score) and general criteria (Evans and Global Leadership Initiative on Malnutrition). These include phenotypic criteria [weight loss, body mass index, (objective) muscle mass assessments, quality of life] and aetiological criteria (disease burden, inflammation, energy expenditure, anorexia and inadequate food intake) and can be incorporated into the nutrition care process (NCP). This informs the nutrition diagnosis of 'chronic disease- or condition-related malnutrition (undernutrition) as related to increased nutrient needs, anorexia or diminished intake due to CC'. Optimal nutrition care and management of CC is multidisciplinary, corrects for increased energy expenditure (via immunonutrition/eicosapentaenoic acid), suboptimal protein/energy intake and poor nutrition quality of life, and includes a physical exercise intervention. Monitoring of intervention efficacy should focus on maintaining or slowing the loss of muscle mass, with weight change as an alternative gross indicator. Dietitians and the NCP can play an essential role with respect to identifying and managing CC, focusing on aspects of nutrition screening, assessment and intervention.
Publisher: Elsevier BV
Date: 06-2020
DOI: 10.1016/J.CMI.2020.01.012
Abstract: Lomentospora prolificans is an emerging cause of serious invasive fungal infections. Optimal treatment of these infections is unknown, although voriconazole-containing treatment regimens are considered the treatment of choice. The objective of this study was to evaluate the role of combination antifungal therapy for L. prolificans infections. We performed a retrospective review of medical records of patients with invasive L. prolificans infection diagnosed between 1 January 2008 and 9 September 2019 that were documented in the FungiScope® registry of rare invasive fungal infections. We compared clinical outcomes between antifungal treatment strategies. Over the study period, 41 in iduals with invasive L. prolificans infection from eight different countries were documented in the FungiScope® registry. Overall, 17/40 (43%) had treatment response/stable disease and 21/40 (53%) had a fatal outcome attributed to invasive fungal infection. Combination antifungal therapy was associated with increased 28-day survival (15/24 survived versus 4/16 receiving monotherapy p 0.027) and the combination voriconazole plus terbinafine trended to be associated with higher rates of treatment success (10/16, 63%, 95% CI 35%-85%) compared with other antifungal treatment regimens (7/24, 29%, 95% CI 13%-51%, p 0.053). In Kaplan-Meier survival analysis there was a higher survival probability in in iduals receiving the voriconazole/terbinafine combination compared with other antifungal regimens (median survival 150 days versus 17 days). While overall mortality was high, combination antifungal treatment, and in particular combination therapy with voriconazole plus terbinafine may be associated with improved treatment outcomes compared with other antifungal regimens for the treatment of invasive L. prolificans infections.
Publisher: Elsevier BV
Date: 02-2011
DOI: 10.1111/J.1600-6143.2010.03375.X
Abstract: While variations in antifungal prophylaxis have been previously reported in lung transplant (LTx) recipients, recent clinical practice is unknown. Our aim was to determine current antifungal prophylactic practice in LTx centers world-wide. One nominated LTx clinician from each active center was invited by e-mail to participate in a web-based survey between September 2009 and January 2010. Fifty-seven percent (58/102) responded. The majority of responses were from medical directors of LTx centers (72.4%), and from the United States (44.8%). Within the first 6 months post-LTx, most centers (58.6%) employed universal prophylaxis, with 97.1% targeting Aspergillus species. Voriconazole alone, and in combination with inhaled hotericin B (AmB), were the preferred first-line agents. Intolerance to side effects of voriconazole (69.2%) was the main reason for switching to alternatives. Beyond 6 months post-LTx, most (51.8%) did not employ antifungal prophylaxis. Fifteen centers (26.0%) conducted routine antifungal therapeutic drug monitoring during prophylactic period. There are differences in strategies employed between U.S. and European centers. Most respondents indicated a need for antifungal prophylactic guidelines. In comparison to earlier findings, there was a major shift toward prophylaxis with voriconazole and an increased use of echinocandins, posaconazole and inhaled lipid formulation AmB.
Publisher: Public Library of Science (PLoS)
Date: 24-09-2014
Publisher: Wiley
Date: 11-07-2012
DOI: 10.1111/J.1399-3062.2012.00762.X
Abstract: Hepatitis B (HBV) reverse seroconversion (RS) in immunocompromised patients with serological evidence of past HBV infection (hepatitis B surface antigen [sAg] negative, core antibody [cAb] positive) has been reported with increasing frequency following allogeneic hematopoietic stem cell transplant (allo-HSCT). We performed a retrospective review of serial HBV serological testing in patients who had undergone allo-HSCT at our center between 2000 and 2006. We identified 12 patients with serological evidence of past HBV, including 1 case of RS. Although 7 of these 12 patients had no changes in serological markers detected after transplantation, 5 of them had declining levels of hepatitis B surface antibodies [sAb], with 2 to < 10 IU/mL. The remaining 4 patients with past HBV had loss of antiHBcAb. An additional 14 patients developed isolated antiHBcAb post allo-HSCT in the setting of receiving HBV screened (HBsAg, antiHBcAb) negative donor stem cells. Monitoring of HBV serological markers (including antiHBsAb) and HBV DNA levels pre allo-HSCT in recipients and donors, and post allo-SCT in recipients, would allow early detection and treatment of RS and identify new acquisition of HBV.
Publisher: Informa UK Limited
Date: 07-2019
Publisher: Elsevier BV
Date: 11-2020
Publisher: Informa UK Limited
Date: 24-03-2017
DOI: 10.1080/14787210.2017.1305886
Abstract: Invasive fungal infections (IFIs) following allogeneic hematopoietic stem cell transplantation (alloHSCT) are associated with a high mortality, and accordingly most alloHSCT recipients receive prophylaxis with antifungal agents. Despite some improvement in outcomes of IFIs over time, they continue to represent substantial clinical risk, mortality, and financial burden. Areas covered: We review the main pathogens responsible for IFIs in recipients of alloHSCT, current treatment recommendations, and discuss clinical and economic considerations associated with voriconazole prophylaxis of IFIs in these patients. Expert commentary: The clinical efficacy of voriconazole appears to be at least equivalent to other antifungal treatments, and generally well tolerated. Overall, benefit-risk balance is favorable, and findings from cost-effectiveness analyses support the use of voriconazole prophylaxis of IFIs in recipients of alloHSCT.
Publisher: Springer Science and Business Media LLC
Date: 30-04-2007
Abstract: We performed a randomized comparison of pre-emptive and empiric antibiotic therapy for adult patients undergoing allogeneic or autologous stem cell transplantation. One hundred and fifty-three patients were randomized to receive cefepime either pre-emptively on the day that neutropenia (ANC<1.0 x 10(9) cells/l) developed irrespective of the presence of fever, or at onset of fever and neutropenia (empiric). Although there was no difference between the two arms in the proportion of patients developing fever or in the median number of days of fever, the time to onset of fever was a mean of 1 day longer in each patient on the pre-emptive arm (log rank P<0.001). The number of patients with bloodstream infections was significantly reduced in those receiving pre-emptive therapy (16/75) compared to the empiric arm (31/76) (P<0.01) but this did not translate into an appreciable clinical benefit as measured by days of hospitalization, time to engraftment, use of additional antimicrobial agents or mortality at 30 days. This study does not support the use of pre-emptive intravenous antibiotic therapy in adult stem cell transplant recipients.
Publisher: Oxford University Press (OUP)
Date: 11-04-2023
DOI: 10.1093/JAC/DKAD085
Abstract: The Antifungal National Antimicrobial Prescribing Survey (AF-NAPS) was developed to undertake streamlined quality audits of antifungal prescribing. The validity and reliability of such tools is not characterized. To assess the validity and reliability of the AF-NAPS quality assessment tool. Case vignettes describing antifungal prescribing were prepared. A steering group was assembled to determine gold-standard classifications for appropriateness and guideline compliance. Infectious diseases physicians, antimicrobial stewardship (AMS) and specialist pharmacists undertook a survey to classify appropriateness and guideline compliance of prescriptions utilizing the AF-NAPS tool. Validity was measured as accuracy, sensitivity and specificity compared with gold standard. Inter-rater reliability was measured using Fleiss’ kappa statistics. Assessors’ responses and comments were thematically analysed to determine reasons for incorrect classification. Twenty-eight clinicians assessed 59 antifungal prescriptions. Overall accuracy of appropriateness assessment was 77.0% (sensitivity 85.3%, specificity 68.0%). Highest accuracy was seen amongst specialist (81%) and AMS pharmacists (79%). Prescriptions with lowest accuracy were in the haematology setting (69%), use of echinocandins (73%), mould-active azoles (75%) and for prophylaxis (71%). Inter-rater reliability was fair overall (0.3906), with moderate reliability amongst specialist pharmacists (0.5304). Barriers to accurate classification were incorrect use of the appropriateness matrix, knowledge gaps and lack of guidelines for some indications. The AF-NAPS is a valid tool, assisting assessors to correctly classify appropriate prescriptions more accurately than inappropriate prescriptions. Specialist and AMS pharmacists had similar performance, providing confidence that both can undertake AF-NAPS audits to a high standard. Identified reasons for incorrect classification will be targeted in the online tool and educational materials.
Publisher: Cold Spring Harbor Laboratory
Date: 28-04-2018
DOI: 10.1101/309674
Abstract: Polymyxin B and E (colistin) have been pivotal in the treatment of extensively drug-resistant (XDR) Gram-negative bacterial infections, with increasing use over the past decade. Unfortunately, resistance to these antibiotics is rapidly emerging. The structurally-related octapeptin C4 (OctC4) has shown significant potency against XDR bacteria, including against polymyxin-resistant (Pmx-R) strains, but its mode of action remains undefined. We sought to compare and contrast the acquisition of XDR Klebsiella pneumoniae (ST258) resistance in vitro with all three lipopeptides to help elucidate the mode of action of the drugs and potential mechanisms of resistance evolution. Strikingly, 20 days of exposure to the polymyxins resulted in a dramatic (1000-fold) increase in the minimum inhibitory concentration (MIC) for the polymyxins, reflecting the evolution of resistance seen in clinical isolates, whereas for OctC4 only a 4-fold increase was witnessed. There was no cross-resistance observed between the polymyxin - and octapeptin-induced resistant strains. Sequencing revealed previously known gene alterations for polymyxin resistance, including crrB , mgrB , pmrB , phoPQ and yciM , and novel mutations in qseC . In contrast, mutations in mlaDF and pqiB , 1genes related to phospholipid transport, were found in octapeptin-resistant isolates. Mutation effects were validated via complementation assays. These genetic variations were reflected in phenotypic changes to lipid A. Pmx-R isolates increased 4-amino-4-deoxy-arabinose fortification to phosphate groups of lipid A, whereas OctC4 induced strains harbored a higher abundance of hydroxymyristate and palmitoylate. The results reveal a differing mode of action compared to polymyxins which provides hope for future therapeutics to combat the increasingly threat of XDR bacteria.
Publisher: Wiley
Date: 05-01-2021
DOI: 10.1111/TID.13548
Abstract: Cytomegalovirus (CMV) reactivation is a frequent complication after allogeneic hematopoietic cell transplant (alloHCT). We analyzed 159 alloHCT recipients with 4409 quantitative CMV viral loads to determine pre‐transplant predictors of CMV reactivation, clinically significant CMV infection (cs‐CMVi, defined as CMV viral load IU/mL), CMV disease, kinetics of spontaneous clearance of CMV, and survival using a standardized pre‐emptive therapy approach to identify at‐risk groups to target prevention strategies. Cs‐CMVi was most common in D−/R+ unrelated donor transplants (URD). Spontaneous CMV clearance occurred in 26% of patients who reached a viral load of 56‐137 IU/mL, 6% at 138‐250 IU/mL and in one patient IU/mL. Median time between the first CMV reactivation ( IU/mL) and a viral load IU/mL was 13 days, whereas the time from the first viral load IU/mL to reach a vial load IU/mL was 4 days. Cs‐CMVi was associated with a significant increase in non‐relapse mortality (NRM) on multivariate analysis. Overall, this study indicates that D−/R+ URD recipients are at high‐risk for cs‐CMVi‐ and CMV‐related mortality, and are potential candidates for targeted CMV prophylaxis. Spontaneous clearance of CMV beyond a viral load of 250 IU/mL is uncommon, suggesting that this could be used as an appropriate threshold to initiate pre‐emptive therapy.
Publisher: Elsevier BV
Date: 09-2014
DOI: 10.1016/J.EJSO.2014.02.241
Abstract: This study aims to describe the incidence of infective complications, including tumour endoprosthesis infection, in a cohort of patients undergoing tumour endoprosthesis surgery in Victoria, Australia. This retrospective cohort study was performed over 15 years (January 1996-December 2010). 121 patients underwent tumour endoprosthesis surgery during the study period. Patients were followed for a median of 34 months (interquartile range [IQR] 17, 80). Overall, 34 patients (28%) experienced infective complications including: bacteraemia in 19 patients (16%) and tumour endoprosthesis infection in 17 (14%). The majority of patients with early and late acute infections (haematogenous) were managed with debridement and retention of the prosthesis in addition to biofilm-active antibiotics. Late chronic infections were predominantly managed by exchange of the prosthesis. The overall success rate of treatment was 71%. The success rate for debridement and retention was 75% compared with 67% for exchange procedures. There is a significant rate of infective complications following tumour endoprosthesis surgery including 14% of patients experiencing infection involving the tumour endoprosthesis. This study is the first to report on outcomes from debridement and retention of the prosthesis which had comparable success rates to other treatment modalities.
Publisher: Wiley
Date: 06-2008
DOI: 10.1111/J.1445-5994.2008.01724.X
Abstract: Persistent or recurrent fevers of unknown origin (PFUO) in neutropenic patients on broad-spectrum antibiotics have traditionally been treated with empirical antifungal therapy (EAFT). The lack of survival benefit seen with the use of hotericin B deoxycholate (AmB-D) as EAFT has been attributed to its toxicities. More recently, newer, less toxic and more expensive antifungal agents such as the lipid formulations of AmB, the newer azoles (fluconazole, itraconazole and voriconazole) and caspofungin have been analysed in a number of EAFT trials. Compared with AmB-D the newer agents have superior safety but are of equivalent efficacy. This lack of survival advantage is related to the fact that the trigger for commencement of EAFT is late and non-specific. Thus, alternative approaches are required. New sensitive serological and molecular tests for the detection of Aspergillus antigens and genomic DNA have been developed and evaluated in accuracy studies. These tests have been incorporated into management strategies (i.e. pre-emptive strategies) to direct antifungal therapy. The pre-emptive approach has been shown to be safe and feasible but its impact on clinically important patient outcomes such as survival is less clear. Other advances include the introduction of effective, non-toxic mould-active antifungal prophylaxis and patient risk-group stratification. In this paper we provide new evidence-based algorithms for the diagnosis and treatment of PFUO in adult patients undergoing stem cell transplantation and chemotherapy for haematological malignancy which incorporate these newer diagnostic tests and are directed by the risk category of the patient and type of antifungal prophylaxis the patient is receiving.
Publisher: Oxford University Press (OUP)
Date: 12-03-2021
DOI: 10.1093/CID/CIAA1865
Abstract: Aspergillus polymerase chain reaction testing of blood and respiratory s les has recently been included in the second revision of the EORTC/MSGERC definitions for classifying invasive fungal disease. This is a result of considerable efforts to standardize methodology, the availability of commercial assays and external quality control programs, and additional clinical validation. This supporting article provides both clinical and technical justifications for its inclusion while also summarizing recent advances and likely future developments in the molecular diagnosis of invasive aspergillosis.
Publisher: Informa UK Limited
Date: 2006
Publisher: Oxford University Press (OUP)
Date: 08-09-2017
DOI: 10.1093/JAC/DKX324
Abstract: To define guidelines for BK polyomavirus (BKPyV)-associated haemorrhagic cystitis (BKPyV-HC) after paediatric and adult HSCT. Review of English literature and evidence-based recommendations by expert consensus. BKPyV-HC occurs in 8%-25% of paediatric and 7%-54% of adult recipients undergoing allogeneic HSCT. Diagnosis requires the triad of cystitis, macro-haematuria and high urine BKPyV loads >7 log10 copies/mL, and exclusion of other relevant aetiologies. BKPyV viraemia is frequent and may serve as a more specific semiquantitative follow-up marker. No randomized controlled trials are available to inform antiviral prophylaxis or treatment. However, hyper-hydration and/or bladder irrigation showed limited prophylactic value. Fluoroquinolones are not effective for prophylaxis or treatment, but rather increase antibiotic resistance. Hyperbaric oxygen or fibrin glue is marginally effective based on small case series from correspondingly equipped centres. Although cidofovir has been reported to improve and/or reduce BKPyV viraemia or viruria, the current data do not support its regular use. BKPyV-HC remains a disabling unmet clinical need in HSCT that requires novel approaches supported by proper clinical trials.
Publisher: Ferrata Storti Foundation (Haematologica)
Date: 04-11-2011
Publisher: Informa UK Limited
Date: 09-04-2014
DOI: 10.3109/10428194.2014.911861
Abstract: Pneumocystis jirovecii pneumonia (PJP) is seen increasingly in non-human immunodeficiency virus (HIV) infected immunocompromised populations, but few cases have previously been reported in association with gemcitabine therapy. We identified all patients administered gemcitabine between March 2009 and December 2012 at the Peter MacCallum Cancer Centre. Cases of PJP were identified using accepted definitions. Overall, 288 gemcitabine-treated patients were identified. Nine cases of PJP were detected, corresponding to an overall rate of 3.1% (95% confidence interval [CI] 1.5-5.7%). PJP was diagnosed during gemcitabine therapy in seven patients, a median of 67 (range 31-109) days from commencement. Among patients with lymphoma, 4/22 developed PJP, corresponding to a rate of 18.2% (95% CI 6.1-38.2%). Fewer infections were associated with breast, lung and gastrointestinal malignancies (1/24 [4.2%], 3/118 [2.5%] and 1/61 [1.6%], respectively). A risk-based tool incorporating concomitant steroid therapy can be applied to target high-risk populations who would benefit from PJP prophylaxis during gemcitabine therapy.
Publisher: Elsevier BV
Date: 2019
DOI: 10.1016/J.CMI.2018.07.011
Abstract: The epidemiology of mucormycosis in the era of modern diagnostics is relatively under-explored. To examine the contemporary epidemiology, clinical manifestations, diagnosis and causative pathogens of mucormycosis. Ovid MEDLINE and Ovid EMBASE from January 2000 to January 2017. Published case reports/series of proven robable mucormycosis. Patients ≥18 years old. Patient characteristics, disease manifestations and causative pathogens were summarized descriptively. Categorical variables were assessed by chi-square test or Fischer's exact test, and continuous variables by the Wilcoxon-Mann-Whitney or Kruskal-Wallis test. Risk factors for the different clinical manifestations of mucormycosis were identified using multivariate logistic regression. Initial database searches identified 3619 articles of which 600 (851 in idual patient cases) were included in the final analysis. Diabetes mellitus was the commonest underlying condition (340/851, 40%) and was an independent risk for rhino-orbital-cerebral mucormycosis (odds ratio (OR) 2.49 95% CI 1.77-3.54 p < 0.001). Underlying haematological malignancy was associated with disseminated infection (OR 3.86 95% CI 1.78-8.37 p 0.001), whereas previous solid organ transplantation was associated with pulmonary (OR 3.19 95% CI 1.50-6.82 p 0.003), gastrointestinal (OR 4.47 95% CI 1.69-11.80 p 0.003), or disseminated (OR 4.20 95% CI 1.68-10.46 p 0.002) mucormycosis. Eight genera (24 species) of Mucorales organisms were identified in 447/851 (53%) cases, of which Rhizopus spp. (213/447, 48%) was the most common. Compared with other genera, Rhizopus spp. was predominantly observed in patients with rhino-orbital-cerebral mucormycosis (75/213, 35% versus 34/234, 15% p < 0.001). Death was reported in 389/851 (46%) patients. Mortality associated with Cunninghamella infections was significantly higher than those caused by other Mucorales (23/30, 71% versus 185/417, 44% p < 0.001). However, Cunninghamella spp. were isolated primarily in patients with pulmonary (17/30, 57%) or disseminated disease (10/30, 33%). Findings from the current review have helped ascertain the association between various manifestations of mucormycosis, their respective predisposing factors and causative organisms.
Publisher: Wiley
Date: 08-2009
Publisher: Informa UK Limited
Date: 04-2011
DOI: 10.1586/ERI.11.24
Abstract: Stenotrophomonas maltophilia is a ubiquitous organism associated with opportunistic infections. In the immunocompromised host, increasing prevalence and severity of illness is observed, particularly opportunistic bloodstream infections and pneumonia syndromes. In this article, the classification and microbiology are outlined, together with clinical presentation, outcomes and management of infections due to S. maltophilia. Although virulence mechanisms and the genetic basis of antibiotic resistance have been identified, a role for standardized and uniform reporting of antibiotic sensitivity is not defined. Infections due to S. maltophilia have traditionally been treated with trimethoprim-sulfamethoxazole, ticarcillin-clavulanic acid, or fluoroquinolone agents. The use of combination therapies, newer fluoroquinolone agents and tetracycline derivatives is discussed. Finally, measures to prevent transmission of S. maltophilia within healthcare facilities are reported, especially in at-risk patient populations.
Publisher: Springer Science and Business Media LLC
Date: 20-04-2023
DOI: 10.1007/S11764-023-01372-7
Abstract: Cancer treatments exert vascular toxic effects that can lead to the development of cardiovascular disease. Exercise training has the potential to prevent or reduce cancer treatment–induced damage to vascular structure and function. This systematic review with meta-analyses aimed to determine the isolated effects of exercise training on vascular outcomes in people with cancer. Seven electronic databases were searched on 20 September 2021 to identify randomised controlled trials, quasi-randomised trials, pilot and cohort studies. Included studies implemented a structured exercise intervention and assessed vascular structure and/or function in people during or following cancer treatment. Meta-analyses examined the effects of exercise training on endothelial function (via brachial artery flow-mediated dilation) and arterial stiffness (via pulse wave velocity). Methodological quality was assessed using the Cochrane Quality Assessment tool and modified Newcastle-Ottawa Quality Appraisal tool. Grading of Recommendations, Assessment, Development and Evaluations framework was used to assess the certainty of evidence. Ten studies (discussed across 11 articles) met the inclusion criteria. Methodological quality of the included studies was moderate (71% average). Exercise improved vascular function when compared to control (standardised mean difference = 0.34, 95% CI (0.01, 0.67) p = 0.044: studies = 5, participants = 171), but not pulse wave velocity (standardised mean difference = − 0.64, 95% CI (− 1.29, 0.02) p = 0.056: studies = 4, participants = 333). The certainty of evidence was moderate for flow-mediated dilation and low for pulse wave velocity. Compared to usual care, exercise training significantly improves flow-mediated dilation (endothelial function) but not pulse wave analysis, in people treated for cancer. Exercise may improve vascular health in in iduals during and following cancer treatment.
Publisher: AMPCo
Date: 11-2012
DOI: 10.5694/MJA12.11199
Publisher: Oxford University Press (OUP)
Date: 02-2023
DOI: 10.1093/OFID/OFAD059
Abstract: Management of Scedosporium/Lomentospora prolificans infections remains challenging. We described predisposing factors, clinical manifestations, and outcomes of these rare mold infections, including predictors of early (1-month) and late (18-month) all-cause mortality and treatment failure. We conducted a retrospective Australian-based observational study of proven robable Scedosporium/L prolificans infections from 2005 to 2021. Data on patient comorbidities, predisposing factors, clinical manifestations, treatment, and outcomes up to 18 months were collected. Treatment responses and death causality were adjudicated. Subgroup analyses, multivariable Cox regression, and logistic regression were performed. Of 61 infection episodes, 37 (60.7%) were attributable to L prolificans. Forty-five of 61 (73.8%) were proven invasive fungal diseases (IFDs), and 29 of 61 (47.5%) were disseminated. Prolonged neutropenia and receipt of immunosuppressant agents were documented in 27 of 61 (44.3%) and 49 of 61 (80.3%) episodes, respectively. Voriconazole/terbinafine was administered in 30 of 31 (96.8%) L prolificans infections, and voriconazole alone was prescribed for 15 of 24 (62.5%) Scedosporium spp infections. Adjunctive surgery was performed in 27 of 61 (44.3%) episodes. Median time to death post–IFD diagnosis was 9.0 days, and only 22 of 61 (36.1%) attained treatment success at 18 months. Those who survived beyond 28 days of antifungal therapy were less immunosuppressed with fewer disseminated infections (both P & .001). Disseminated infection and hematopoietic stem cell transplant were associated with increased early and late mortality rates. Adjunctive surgery was associated with lower early and late mortality rates by 84.0% and 72.0%, respectively, and decreased odds of 1-month treatment failure by 87.0%. Outcomes associated with Scedosporium/L prolificans infections is poor, particularly with L prolificans infections or in the highly immunosuppressed population.
Publisher: Elsevier BV
Date: 02-2019
Publisher: Oxford University Press (OUP)
Date: 08-04-2020
Abstract: The timing and necessity of repeated blood cultures (BCs) in children with cancer and febrile neutropenia (FN) are unknown. We evaluated the diagnostic yield of BCs collected pre- and post-empiric FN antibiotics. Data collected prospectively from the Australian Predicting Infectious ComplicatioNs in Children with Cancer (PICNICC) study were used. Diagnostic yield was calculated as the number of FN episodes with a true bloodstream infection (BSI) detected ided by the number of FN episodes that had a BC taken. A BSI was identified in 13% of 858 FN episodes. The diagnostic yield of pre-antibiotic BCs was higher than of post-antibiotic cultures (12.3% vs 4.4%, P & .001). Two-thirds of the post-antibiotic BSIs were associated with a new episode of fever or clinical instability, and only 2 new BSIs were identified after 48 hours of empiric antibiotics and persistent fever. A contaminated BC was identified more frequently in post-antibiotic cultures. In the absence of new fever or clinical instability, BCs beyond 48 hours of persistent fever have limited yield. Opportunity exists to optimize BC collection in this population and reduce the burden of unnecessary tests on patients, healthcare workers, and hospitals.
Publisher: Wiley
Date: 15-06-2013
DOI: 10.1111/EJH.12135
Publisher: Informa UK Limited
Date: 20-11-2015
Publisher: Wiley
Date: 07-12-2021
DOI: 10.1111/TID.13531
Abstract: Cytomegalovirus (CMV) is a significant cause of morbidity and mortality in the immunocompromised host. Atypical presentations which include pseudotumors or “cancer mimics” have been described. The etiology of these lesions remains unclear. The authors describe two previously unpublished cases that have arisen in the context of newer immunomodulating therapy and review the existing non‐HIV‐associated CMV pseudotumors described in the literature.
Publisher: Informa UK Limited
Date: 04-01-2016
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2022
DOI: 10.1161/STROKEAHA.122.039575
Abstract: Cerebral venous thrombosis (CVT) due to vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe condition, with high in-hospital mortality rates. Here, we report clinical outcomes of patients with CVT-VITT after SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccination who survived initial hospitalization. We used data from an international registry of patients who developed CVT within 28 days of SARS-CoV-2 vaccination, collected until February 10, 2022. VITT diagnosis was classified based on the Pavord criteria. Outcomes were mortality, functional independence (modified Rankin Scale score 0–2), VITT relapse, new thrombosis, and bleeding events (all after discharge from initial hospitalization). Of 107 CVT-VITT cases, 43 (40%) died during initial hospitalization. Of the remaining 64 patients, follow-up data were available for 60 (94%) patients (37 definite VITT, 9 probable VITT, and 14 possible VITT). Median age was 40 years and 45/60 (75%) patients were women. Median follow-up time was 150 days (interquartile range, 94–194). Two patients died during follow-up (3% [95% CI, 1%–11%). Functional independence was achieved by 53/60 (88% [95% CI, 78%–94%]) patients. No new venous or arterial thrombotic events were reported. One patient developed a major bleeding during follow-up (fatal intracerebral bleed). In contrast to the high mortality of CVT-VITT in the acute phase, mortality among patients who survived the initial hospitalization was low, new thrombotic events did not occur, and bleeding events were rare. Approximately 9 out of 10 CVT-VITT patients who survived the acute phase were functionally independent at follow-up.
Publisher: Wiley
Date: 10-10-2016
DOI: 10.1111/EJH.12813
Abstract: Bloodstream infections (BSIs) are a significant complication of treatment for multiple myeloma (MM). The objective of this study was to define the epidemiology of BSI with current era MM treatment regimens, including immunomodulatory drugs, proteasome inhibitors and autologous haematopoietic stem cell transplantation (ASCT). Clinical and microbiology records of patients with MM diagnosed between 2008 and 2012 were reviewed using a standardised tool to capture patient demographics, myeloma characteristics and BSI characteristics (type, severity, outcomes). Conditional risk set modelling was used to determine clinical predictors of BSI. Of 199 studied patients, 71 (35.6%) had confirmed BSI (98 infection episodes). Peak incidence was 65.1 infections/100 patient-years at 4-6 months following MM diagnosis with a late peak at 64-66 months. Gram-positive pathogens were responsible for the majority (54.5%) of infections during induction, whilst gram-negative pathogens were responsible for the majority (57.7%) of infections during disease progression. Overall, Escherichia coli was the most frequently identified pathogen. Streptococcus pneumoniae comprised 6.1% of all BSIs at a median of 7.5 months following MM diagnosis. Highest rates of ICU admission (23.1%) and mortality (11.5%) were seen with BSIs in patients with progressive disease. Recent ASCT was independently associated with increased BSI risk (HR 3.09, P = 0.05). Treatment of progressive disease is a high-risk period for infection, evidenced by high proportions of BSI due to gram-negative pathogens and S. pneumoniae. Targeted evaluation of preventative strategies (prophylaxis, vaccination) to reduce morbidity and mortality during this period is required.
Publisher: Oxford University Press (OUP)
Date: 12-01-2012
DOI: 10.1093/JAC/DKR577
Publisher: American Society for Microbiology
Date: 06-1993
Abstract: Cytomegalovirus (CMV) often persists in the lungs of marrow transplant patients with CMV pneumonia, despite ganciclovir (GCV) treatment. To determine whether GCV resistance contributes to viral persistence, the susceptibilities of CMV isolates from diagnostic bronchoalveolar lavage s les and CMV isolates obtained during treatment or from autopsy lung tissue from 12 patients were compared by DNA hybridization. Resistance (50% effective dose, 12 microM) was detected in an isolate from only one patient who had also received several courses of GCV. GCV resistance did not explain the persistence of CMV in the lung.
Publisher: Wiley
Date: 02-2012
DOI: 10.1111/J.1445-5994.2011.02450.X
Abstract: FDG-PET/CT is widely used in the management of a variety of malignancies with excellent overall accuracy, despite the potential for false positive results related to infection and inflammation. As cancer patients can develop clinically inapparent infections, we evaluated the prevalence and nature of incidental findings reported to be suggestive of infections that had been identified during clinical cancer staging with FDG-PET/CT. The study involved a retrospective analysis of 60 patients managed primarily at our facility from a total of 121 cases identified as having possible infection on clinical reporting of more than 4500 cancer staging investigations performed during the calendar year of 2008. Occult infections were uncommon overall (≤1%), but most often because of pneumonia (31.6%), upper respiratory tract infections (21.1%) or wound infections (15.8%). Abnormal scans contributed to patients' management in 52.7% of cases. Two out of 13 patients whose scan abnormalities were not investigated further had worsening changes on repeated scan and one of these patients had clinical deterioration. In patients with FDG-PET/CT scans suggestive of infection and in whom a final diagnosis could be reached, the positive predictive value for FDG-PET/CT scans was 89% suggesting that abnormal scans indicative of infection should be investigated further in this population.
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.VACCINE.2018.02.098
Abstract: Healthcare workers (HCWs) at an Australian cancer centre were evaluated using a voluntary declination form program to determine factors contributing to declination of annual influenza vaccination. Overall, 1835/2041 HCWs (89.9%) completed a consent or declination form 1783 were vaccinated and 52 declined. Staff roles with minimal patient contact were significantly associated with lower vaccine uptake (adjusted odds ratio 0.48, 95% confidence interval 0.23-0.99). Reasons for vaccine refusal included personal choice (41%), previous side-effect/s (23.1%), and medical reasons (23.1%). Of these, a large proportion may not be amenable to intervention, and this must be considered in setting threshold targets for future c aigns.
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.BBMT.2017.07.025
Abstract: Opportunistic infections such as cytomegalovirus (CMV) reactivation and invasive fungal disease (IFD) cause significant morbidity and mortality to recipients of hematopoietic stem cell transplant (HSCT). We aimed to characterize the risk and relationship of CMV reactivation post-HSCT to IFD in the current era of CMV viral load monitoring using highly sensitive plasma DNA. A multicenter, retrospective, cohort study was conducted of consecutive patients undergoing allogeneic HSCT from January 2006 to December 2010 in Melbourne, Australia. CMV reactivation was defined as detection of plasma CMV DNA ≥ 546 IU/mL or development of CMV disease. IFD was classified in accordance with current international consensus guidelines. Of the 419 study participants, the median age was 44 years (IQR, 34 to 54), and CMV reactivation occurred in 106 participants (25%) at a median time of 56 days (IQR, 45 to 79). Thirty-eight participants (9.1%) were identified with 41 cases of IFD (n = 22 proven, n = 8 probable, n = 11 possible) at a median time of 76 days (IQR, 24 to 344). The incidence of IFD was higher in participants with CMV reactivation compared with no CMV reactivation (15% versus 7%, P = .012). In a multivariate analysis CMV reactivation remained an independent risk factor for IFD (hazard ratio, 3.7 95% CI, 1.6 to 8.5 P = .002). The cumulative incidence of all IFD in patients with and without CMV reactivation using a competing risk regression was a hazard ratio of 2.2 (95% CI, 1.2 to 4.1 P = .017) and for late-onset IFD was a hazard ratio of 3.95 (95% CI, 1.7 to 9 P = .001). The median time to IFD onset was longer in participants with than without CMV reactivation (184 versus 37 days, P = .03). The peak viral load, detection of any level of viremia, and experiencing more than 1 episode of CMV reactivation were not associated with development of IFD. CMV reactivation in HSCT recipients in the post-transplant period is associated with an increased risk of developing late-onset IFD. Further research is warranted to understand the interaction between these 2 important infectious complications.
Publisher: Elsevier BV
Date: 2006
Publisher: American Society for Microbiology
Date: 05-2008
DOI: 10.1128/AAC.01388-07
Abstract: The efficacy of voriconazole in 107 patients with scedosporiosis was analyzed. Principal infection sites were the lungs/sinuses (24%), central nervous system (CNS) (20%), and bone (18%), while 21% of patients had disseminated infection. Solid organ transplantation (22%), hematological malignancy (21%), and surgery/trauma (15%) were the predominant underlying conditions. A successful therapeutic response was achieved in 57% of patients (median, 103 therapy days), with % of those responding receiving ≥28 days of therapy. Patients receiving primary therapy showed a 61% response versus 56% for the others. The best therapeutic responses were seen for skin/subcutaneous (91%) or bone (79%) infections, and the lowest for CNS infections (43%). Patients without major immune suppression (72%) or those with solid organ transplantation (63%) or various hematological conditions (60%) showed the best responses by underlying condition. Median known survival time was 133 days (therapy successes, 252 days failures, 21 days). In all, 43 (40%) patients died, 73% due to scedosporiosis. Patients with Scedosporium prolificans infection had significantly reduced survival times ( P = 0.0259) and were more likely to die from fungal infection ( P = 0.002) than were Scedosporium apiospermum -infected patients. In a subset of 43 patients where voriconazole baseline MICs were available, response to voriconazole was higher for S. apiospermum -infected patients (54% response MIC 50 , 0.25 μg/ml) than for S. prolificans -infected patients (40% response MIC 50 , 4.0 μg/ml). Voriconazole demonstrated clinically useful activity in the treatment of both S. apiospermum and S. prolificans infections and was well tolerated.
Publisher: Oxford University Press (OUP)
Date: 25-01-2017
DOI: 10.1093/JAC/DKW580
Publisher: MDPI AG
Date: 28-02-2022
DOI: 10.3390/NANO12050810
Abstract: The recyclable utilization of waste biomass is increasingly important for the development of a sustainable society. Here, the sawdust-derived activated carbon (SD-AC) has been prepared via a convenient H3PO4-based activation method and further trialed as an electrode for use as a high-performance symmetric supercapacitor. The as-prepared SD-AC possesses a hierarchically porous structure with micropores (0.55 nm) and mesopores (2.58 nm), accounting for its high specific surface area of 621 m2 g−1, with a pore volume of 0.35 cm3 g−1. Such a hierarchically porous structure can offer a favorable pathway for fast ion penetration and transportation, enhancing its electrochemical performance. As a result, the SD-AC electrode exhibits a maximum specific capacitance of up to 244.1 F g−1 at 1.0 A g−1, a high rate capability (129.06 F g−1 at 20 A g−1), and an excellent cycling performance, with 87% retention over 10,000 cycles at 10 A g−1. Of particular note is that the SD-AC-based symmetric supercapacitor achieves a maximum energy density of 19.9 Wh kg−1 at the power density of 650 W kg−1, with a long-term cycle lifespan. This work showcases the recyclable utilization of waste biomass for the preparation of high-value activated carbon for efficient energy storage.
Publisher: Springer Science and Business Media LLC
Date: 11-07-2015
Publisher: Elsevier BV
Date: 02-2016
Publisher: Elsevier BV
Date: 09-2007
DOI: 10.1016/J.TUBE.2007.05.013
Abstract: Active tuberculosis (TB) infection including asymptomatic and extrapulmonary disease may be detected with 18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT). This report highlights the promising role of FDG-PET/CT for evaluation of TB in high-risk, immunocompromised patients with cancer. PET/CT performed for cancer evaluation may detect asymptomatic infection and guide definitive diagnosis. It may also be a useful tool in the assessment of latent TB, to exclude active disease prior to treatment. PET/CT has potential for monitoring response to anti-tuberculosis treatment. Metabolic response may indicate clinical response and guide duration of anti-microbial therapy.
Publisher: Elsevier BV
Date: 07-2014
DOI: 10.1016/J.DIAGMICROBIO.2014.03.020
Abstract: Interpretation of Aspergillus galactomannan (GM) and PCR results in bronchoalveolar lavage (BAL) fluid for the diagnosis of invasive pulmonary aspergillosis (IPA) in patients with haematological malignancies requires clarification. A total of 116 patients underwent BAL for investigation of new lung infiltrates: 40% were neutropenic, 68% and 36% were receiving mould-active antifungal agents and β-lactam antibiotics. The diagnosis of proven IPA (n = 3), probable IPA (n = 15), and possible invasive fungal disease (IFD, n = 50) was made without inclusion of GM results. BAL GM (at cut-off of 0.8) had lower diagnostic sensitivity for IPA than PCR (61% versus 78%) but higher specificity (93% versus 79%). Both tests had excellent negative predictive values (85-90%), supporting their utility in excluding IPA. The use of BAL GM and PCR results increased the certainty of Aspergillus aetiology in 7 probable IPA cases where fungal hyphae were detected in respiratory s les by microscopy, and upgraded 24 patients from possible IFD to probable IPA. Use of BAL GM and PCR improves the diagnosis of IPA.
Publisher: Wiley
Date: 12-2014
DOI: 10.1111/IMJ.12595
Abstract: There is a strong argument for the use of antifungal prophylaxis in high-risk patients given the significant mortality associated with invasive fungal disease, the late identification of these infections, and the availability of safe and well-tolerated prophylactic medications. Clinical decisions about which patients should receive prophylaxis and choice of antifungal agent should be guided by risk stratification, knowledge of local fungal epidemiology, the efficacy and tolerability profile of available agents, and estimates such as number needed to treat and number needed to harm. There have been substantial changes in practice since the 2008 guidelines were published. These include the availability of new medications and/or formulations, and a focus on refining and simplifying patient risk stratification. Used in context, these guidelines aim to assist clinicians in providing optimal preventive care to this vulnerable patient demographic.
Publisher: Wiley
Date: 17-04-2015
DOI: 10.1111/MYC.12324
Abstract: The emergence of triazole resistance, including multi-triazole-resistant Aspergillus fumigatus is being reported around the world, but there has been little evidence of this problem to date in Australia. Here we describe a retrospective search of antifungal susceptibility results of all Australian clinical A. fumigatus isolates referred to the National Mycology Reference Centre, Adelaide, Australia between 2000 and 2013, yielding 13 isolates with elevated minimum inhibitory concentrations to itraconazole, posaconazole and/or voriconazole. Four isolates were found to be Aspergillus lentulus, a closely related, morphologically similar species known to have reduced susceptibility to triazoles. Analysis of the cyp51A gene of nine confirmed A. fumigatus isolates revealed two carrying the TR34 /L98H mutation, one apparently locally acquired in 2004, and the other probably acquired abroad in 2012. Four isolates possessed the G54R, F46Y, Y431S and G448S mutations, respectively, whereas three isolates did not possess known cyp51A resistance mutations, raising the possibility of other, undetected resistance mechanisms. Routine antifungal susceptibility testing is definitively recommended in patients on long term and sub-therapeutic triazole therapy with breakthrough Aspergillus infection and recommended for all clinically relevant A. fumigatus isolates.
Publisher: Wiley
Date: 16-08-2020
DOI: 10.1111/TID.13441
Publisher: Informa UK Limited
Date: 2004
DOI: 10.1080/1042819031000149449
Abstract: We describe 3 cases of fatal but clinically unsuspected anerobic bacteremia amongst hematopoietic stem cell transplant (HSCT) recipients treated empirically for fever and neutropenia with third or fourth generation cephalosporins. All patients had diarrhea but none had classical findings of neutropenic enterocolitis. HSCT recipients with fever, neutropenia and gastrointestinal tract symptoms such as abdominal pain or diarrhea or with septic shock despite broad spectrum antibiotics should receive an antimicrobial agent with anerobic activity.
Publisher: Wiley
Date: 12-2014
DOI: 10.1111/IMJ.12596
Abstract: Invasive fungal disease (IFD) causes significant morbidity and mortality in patients undergoing allogeneic haemopoietic stem cell transplantation or chemotherapy for haematological malignancy. Much of these adverse outcomes are due to the limited ability of traditional diagnostic tests (i.e. culture and histology) to make an early and accurate diagnosis. As persistent or recurrent fevers of unknown origin (PFUO) in neutropenic patients despite broad-spectrum antibiotics have been associated with the development of IFD, most centres have traditionally administered empiric antifungal therapy (EAFT) to patients with PFUO. However, use of an EAFT strategy has not been shown to have an overall survival benefit and is associated with excessive antifungal therapy use. As a result, the focus has shifted to developing more sensitive and specific diagnostic tests for early and more targeted antifungal treatment. These tests, including the galactomannan enzyme-linked immunosorbent assay and Aspergillus polymerase chain reaction (PCR), have enabled the development of diagnostic-driven antifungal treatment (DDAT) strategies, which have been shown to be safe and feasible, reducing antifungal usage. In addition, the development of effective antifungal prophylactic strategies has changed the landscape in terms of the incidence and types of IFD that clinicians have encountered. In this review, we examine the current role of EAFT and provide up-to-date data on the newer diagnostic tests and algorithms available for use in EAFT and DDAT strategies, within the context of patient risk and type of antifungal prophylaxis used.
Publisher: Wiley
Date: 12-2014
DOI: 10.1111/IMJ.12597
Abstract: Pathogenic yeast forms are commonly associated with invasive fungal disease in the immunocompromised host, including patients with haematological malignancies and patients of haemopoietic stem cell transplants. Yeasts include the Candida spp., Cryptococcus spp., Pneumocystis jirovecii and some lesser-known pathogens. Candida species remain the most common cause of invasive yeast infections (and the most common human pathogenic fungi). These guidelines present evidence-based recommendations for the antifungal management of established, invasive yeast infections in adult and paediatric patients in the haematology/oncology setting. Consideration is also given to the critically ill patient in intensive care units, including the neonatal intensive care unit. Evidence for 'pre-emptive' or 'diagnostic-driven antifungal therapy' is also discussed. For the purposes of this paper, invasive yeast diseases are categorised under the headings of invasive candidiasis, cryptococcosis and uncommon yeast infections. Specific recommendations for the management of Pneumocystis jirovecii are presented in an accompanying article (see consensus guidelines by Cooley et al. appearing elsewhere in this supplement).
Publisher: Elsevier BV
Date: 02-2014
Abstract: Australian guidelines for healthcare worker (HCW) vaccination were updated in 2010, and pre-employment assessment of new employees has previously been identified as a priority. We determined the vaccination status of a cohort of existing HCWs at a tertiary hospital in Melbourne, Victoria. Random s ling of HCWs employed prior to 2006 with unknown/incomplete immunisation status was conducted between April and August 2011. Immunity to vaccine-preventable diseases (VPDs) was determined serologically (hepatitis B, varicella, measles, mumps, rubella) and by questionnaire (diphtheria, tetanus and pertussis), with vaccination by a nurse immuniser. Overall, 95 HCWs were evaluated. Mean age and duration of employment were 47.2 and 12.6 years, respectively. Forty-seven staff (49%) required vaccination to comply with Australian immunisation guidelines: 18% were non-immune to hepatitis B, 2% to varicella, 8% to measles, 19% to mumps and 13% to rubella. HCWs without serological hepatitis B immunity were all staff with clinical roles. Total costs were $7,527.34 (mean $222.79/HCW). Immunity to VPDs among existing HCWs was inadequate. About half assessed HCWs were non-immune to at least one VPD, and non-immunity to hepatitis B was high. A comprehensive assessment strategy for existing employees is required to enhance vaccination coverage and compliance with national guidelines. Adequately resourced 'look-back' immunisation assessment programs are required to reduce the risks of VPDs among existing staff and patients. Review of current approaches and national consensus regarding the need for mandatory strategies would assist this process.
Publisher: Oxford University Press (OUP)
Date: 06-1995
DOI: 10.1093/INFDIS/171.6.1545
Abstract: A randomized, double-blind, placebo-controlled trial assessed the efficacy and toxicity of 400 mg/day fluconazole in preventing fungal infections during the first 75 days after marrow transplantation. During prophylaxis, systemic fungal infections occurred in 10 (7%) of 152 fluconazole-treated patients compared with 26 (18%) of 148 placebo-treated patients (P = .004). There were no Candida albicans infections in fluconazole recipients compared with 18 in placebo recipients (P < .001) and no significant increase in Candida infections other than C. albicans. Fluconazole also significantly reduced the incidence of superficial fungal infections (P < .001), fungal colonization (P = .037), and empiric hotericin B use (P = .005). The probability of survival was improved in fluconazole recipients, in whom 31 deaths occurred up to day 110 after transplantation compared with 52 deaths in placebo recipients (P = .004). No clinically significant toxicity was detected with fluconazole use. Prophylactic fluconazole was safe and significantly reduced systemic fungal infections with other benefits, including improved survival at day 110 after marrow transplantation.
Publisher: Informa UK Limited
Date: 2003
DOI: 10.1080/1042819031000111071
Abstract: Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating neurological disorder caused by JC virus. Immunocompromised patients such as those with chronic lymphocytic leukemia, AIDS and following organ transplantation are at increased risk. We report a patient with PML complicating longstanding Waldenström's macroglobulinaemia. Although PML is a rare occurrence, the newer highly immunosuppressive treatment approaches for patients with lymphoproliferative disorders necessitate a high index of clinical suspicion. The diagnosis should be considered in patients with compatible clinical features who have received long-term immunosuppressive treatments recognized to impair cellular immunity.
Publisher: Elsevier BV
Date: 04-2023
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 06-2020
Publisher: Informa UK Limited
Date: 22-04-2018
Publisher: Wiley
Date: 2008
Publisher: Springer Science and Business Media LLC
Date: 08-12-2010
Publisher: Wiley
Date: 27-03-2007
Publisher: Wiley
Date: 12-2014
DOI: 10.1111/IMJ.12593
Abstract: This article introduces the second revision of the Australian and New Zealand consensus guidelines for the use of antifungal agents in the haematology/oncology setting. The current update occurs within the context of a growing population at risk of invasive fungal disease, improved understanding of risk factors, availability of new diagnostic tests, a much-expanded evidence base and changing clinical paradigms. Here, we provide an overview of the history and purpose of the guidelines, including changes in scope since the last clinical update was published in 2008. The process for development, and for enabling review of draft recommendations by end-users and other relevant stakeholders, is described. The approach to assigning levels of evidence and grades of recommendation is also provided, along with a comparison to international grading systems.
Publisher: Wiley
Date: 12-2014
DOI: 10.1111/IMJ.12594
Abstract: This article reports the findings of a survey developed to assess the current use of antifungal prophylaxis among haematology and infectious disease clinicians across Australia and New Zealand, and their alignment with existing consensus guidelines for the use of antifungal agents in the haematology/oncology setting (published 2008). Surveyed clinicians largely followed the current recommendations for prophylaxis in the setting of induction chemotherapy for acute myeloid leukaemia, as well as autologous and low-risk allogeneic haemopoietic stem cell transplantation (HSCT). In keeping with guideline recommendations, posaconazole was the agent used by most centres for high-risk allogeneic HSCT. However, its routine continuation for 75-100 days post-transplantation without de-escalation suggested use beyond those indications described in the 2008 guidelines, namely pre-engraftment neutropenia and graft-versus-host disease. Variations in practice were observed in other settings, such as acute lymphoblastic leukaemia and myelodysplastic syndrome, reflecting the general lack of evidence for antifungal prophylaxis in these patient populations and changing perceptions of risk. With regard to the availability of testing in cases of suspected breakthrough IFD, 40% of centres did not have access to investigative bronchoscopy within 48 h of referral, and results of Aspergillus galactomannan (GM), fungal polymerase chain reaction and therapeutic drug monitoring (TDM) were not available within 48 h in 83%, 90% and 85% of centres respectively. The survey's findings will influence the recommendations provided in the updated 2014 consensus guidelines for the use of antifungal agents in the haematology/oncology setting.
Publisher: Wiley
Date: 06-2013
DOI: 10.1111/IMJ.12110
Abstract: Micafungin demonstrated non-inferiority to caspofungin as definitive therapy for candidaemia and invasive candidiasis (IC) in a major randomised clinical trial. The aim of this study was to investigate if micafungin is a cost-saving option compared with caspofungin for treating candidaemia and IC. A decision analytical model was constructed to capture downstream consequences of using either agent as initial therapy for candidaemia and IC. The main outcomes were treatment success and treatment failure (i.e. death, mycological persistence, emergent infection, clinical failure but microbiological success). Outcome probabilities and treatment pathways were derived from the literature. Cost inputs were from the latest Australian resources, and resource use was estimated by expert panel. The analysis was from the Australian hospital perspective. Sensitivity analyses using Monte Carlo simulation were conducted. Micafungin (AU$52 816) was associated with a lower total cost than caspofungin (AU$52 976), with a net cost-saving of $160 per patient. This was primarily due to the lower cost associated with alternative antifungal treatment in the micafungin arm. Hospitalisation was the main cost-driver for both arms. The model outcome was most sensitive to the proportion of treatment success in the micafungin arm. Uncertainty analysis demonstrated that micafungin had a 58% chance of being cost-saving compared with caspofungin. Micafungin was cost-equivalent to caspofungin in treating candidaemia and IC, with variation in drug acquisition cost the critical factor.
Publisher: Oxford University Press (OUP)
Date: 29-05-2012
DOI: 10.1093/JAC/DKS210
Abstract: Scedosporium species are increasingly recognized as a cause of invasive mould disease in haematology patients, but little is known about the hospitalization costs and outcomes attributable to invasive scedosporiosis (SCEDO). A retrospective case-control study was undertaken during 2002-10 to determine the attributable inpatient costs, length of stay (LOS) and mortality associated with SCEDO in haematology patients. Case patients with SCEDO (n = 30) were matched 1 : 2 to controls (n = 60) according to haematological diagnosis, admission year and age. Diagnostics, antifungal drugs, ward and other SCEDO-related costs were estimated using actual cost data. Median regression modelling was used to adjust for variables that were not accounted for in the matched-pairs analysis. The crude total median cost of treating SCEDO was AU$32 182 per patient versus AU$17 424 per control. In multivariable analysis, SCEDO was associated with median excess costs of AU$23 611 (95% CI = AU$17 992-AU$29 231 P < 0.001), approximating US$15 509 at purchasing power parity, with prolonged LOS of 13 days (95% CI = 8.2-17.8 days P < 0.001). Exclusion of cases and matched pairs with early death further increased the median excess cost and LOS. The cost differential was driven by ward costs (64%, P = 0.005) and antifungal treatment costs (29%, P < 0.001). The all-cause inpatient mortality was 38 times higher for the SCEDO cases versus the control group (63.3% versus 1.7% P < 0.001). SCEDO has substantial impact on hospital resource consumption, LOS and mortality in haematology patients. Risk factors and preventative measures for SCEDO should be further studied.
Publisher: Elsevier BV
Date: 09-2016
DOI: 10.1016/J.JGO.2016.02.006
Abstract: The management of older persons with cancer has become a major public health concern in developed countries because of the aging of the population and the steady increase in cancer incidence with advancing age. Nurses and allied health care professionals are challenged to address the needs of this growing population. The International Society of Geriatric Oncology (SIOG) Nursing and Allied Health (NAH) Interest Group described key issues that nurses and allied health care professionals face when caring for older persons with cancer. The domains of the Geriatric Assessment (GA) are used as a guiding framework. The following geriatric domains are described: demographic data and social support, functional status, cognition, mental health, nutritional status, fatigue, comorbidities, polypharmacy, and other geriatric syndromes (e.g. falls, delirium). In addition to these geriatric domains, quality of life (QoL) is described based on the overall importance in this particular population. Advice for integration of assessment of these geriatric domains into daily oncology practice is made. Research has mainly focused on the role of treating physicians but the involvement of nurses and allied health care professionals is crucial in the care of older persons with cancer through the GA process. The ability of nurses and allied health care professionals to perform this assessment requires specialized training and education beyond standard oncology knowledge.
Publisher: Ferrata Storti Foundation (Haematologica)
Date: 23-07-2015
Publisher: Informa UK Limited
Date: 31-08-2015
DOI: 10.1586/14787210.2015.1083858
Abstract: Viral infections are a major cause of morbidity and mortality in patients with myeloma. Over the last decade, treatment of myeloma has undergone a paradigm shift with the use of immunomodulatory drugs, proteasome inhibitors and autologous stem cell transplantation, resulting in changes to risk periods and risk factors for viral infection. Viral infections affecting this patient group fall broadly into reactivation of latent viral infections (e.g., varicella zoster and hepatitis B) and acquisition of acute viral respiratory infections. The periods following autologous stem cell transplantation and progressive disease are identified as increased risk for viral infections. This review focuses on evidence-based prevention strategies for key viral infections, particularly approaches to prophylaxis and immunization. Recommended prevention strategies are summarized using a risk-stratified approach. Further studies evaluating preventative measures for newly identified risk periods are required.
Publisher: Wiley
Date: 06-12-2012
DOI: 10.1111/J.1365-2648.2011.05888.X
Abstract: In this article, we discuss the use of the Precede-Proceed model when investigating health promotion options for breast cancer survivors. Adherence to recommended health behaviours can optimize well-being after cancer treatment. Guided by the Precede-Proceed approach, we studied the behaviours of breast cancer survivors in our health service area. The interview data from the cohort of breast cancer survivors are used in this article to illustrate the use of Precede-Proceed in this nursing research context. Interview data were collected from June to December 2009. We also searched Medline, CINAHL, PsychInfo and PsychExtra up to 2010 for relevant literature in the English language to interrogate the data from other theoretical perspectives. The Precede-Proceed model is theoretically complex. The deductive analytic process guided by the model usefully explained some of the health behaviours of cancer survivors, although it could not explicate many other findings. A complementary inductive approach to the analysis and subsequent interpretation by way of Uncertainty in Illness Theory and other psychosocial perspectives provided a comprehensive account of the qualitative data that resulted in contextually relevant recommendations for nursing practice. Nursing researchers using Precede-Proceed should maintain theoretical flexibility when interpreting qualitative data. Perspectives not embedded in the model might need to be considered to ensure that the data are analysed in a contextually relevant way. Precede-Proceed provides a robust framework for nursing researchers investigating health promotion in cancer survivors however, additional theoretical lenses to those embedded in the model can enhance data interpretation.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-1992
Publisher: Springer Science and Business Media LLC
Date: 19-12-2008
DOI: 10.1007/S00520-008-0561-7
Abstract: Central venous catheter (CVC)-related bloodstream infection (CR-BSI) is a significant complication in hematology patients. A range of CVC devices may be used, and risks for the development of complications are not uniform. The objectives of this study were to determine the natural history and rate of CVC-related complications and risk factors for CR-BSI and to compare device-specific complications in a hematology population. An observational cohort of patients with hematologic malignancy was prospectively studied following CVC insertion. Participants were reviewed until a CVC-related complication necessitated device removal, completion of therapy, death, or defined end-of-study date. The National Nosocomial Infection Surveillance definition for CR-BSI was used. Overall and device-specific rates of infective and noninfective complications were calculated and potential risk factors were captured. One hundred six CVCs (75 peripherally inserted central venous catheters [PICCs], 31 nontunneled CVCs) were evaluated in 66 patients, over 2,399 CVC days. Thrombosis occurred in 16 cases (15.1%), exit-site infection in two (1.9%), and CR-BSI in 18 (7.5 per 1,000 CVC days). No significant differences were found when complication rates in PICC and nontunneled devices were compared. An underlying diagnosis of acute myeloid leukemia was negatively associated with CR-BSI (odds ratio (OR) 0.14, p = 0.046), and a previous diagnosis of fungal infection was associated with infection (OR 22.82, p = 0.031). CR-BSI rates in our hematology population are comparable to prior reports. A low rate of exit-site infection and high proportion of thrombotic complications were observed. No significant differences in thrombotic or infective complications were evident when PICC and nontunneled devices were compared. PICC devices are a practical and safe option for management of hematology patients.
Publisher: Informa UK Limited
Date: 22-10-2016
DOI: 10.1080/14787210.2016.1245613
Abstract: Due to increasing intensity and complexity of therapies and longer survivorship, many patients with haematologic malignancy (HM) are at risk of invasive fungal disease (IFD). Mortality from IFD is high and treatment of an episode of IFD results in an excess length of hospital stay and costs and delays delivery of curative therapy of the underlying haematologic condition. Therefore, prevention and early recognition and treatment of IFD are crucial. Areas covered: Risk factors particular to certain HMs and haematopoietic stem cell transplantation, as well as those risk factors universal to all HM groups are examined. Expert commentary: Risk stratification identifies those patients who would benefit most from mould active versus yeast active prophylaxis and those who can be safely managed with monitoring and clinically driven interventions for IFD. This approach aids in antifungal stewardship.
Publisher: Informa UK Limited
Date: 11-11-2011
Publisher: Wiley
Date: 31-01-2008
Publisher: Informa UK Limited
Date: 28-08-2015
Publisher: Wiley
Date: 09-2013
DOI: 10.1111/IMJ.12228
Abstract: Although Australian consensus guidelines support the use of ambulatory care strategies for management of adult patients with low-risk neutropenic fever (NF), few centres have successfully implemented viable programmes. To study the feasibility of an early discharge programme for adult patients with low-risk NF and assess organisational factors likely to influence successful implementation across participating Victorian hospitals. Four hospitals participated in an organisational readiness assessment preceding selection of a pilot site for programme implementation. Prospective baseline auditing of current practice (i.e. inpatient care until resolution of NF) across three hospitals preceded programme implementation and evaluation. Barriers and facilitators to successful implementation were identified. One hundred and seventeen NF episodes were evaluated during audit phases. The frequency of low-risk NF presentations eligible for early discharge was low (less than two episodes per week). The programme reduced median (interquartile range) duration of parenteral antibiotics and length of stay for eligible patients (n = 11) from 4 (4, 5) days at baseline to 1 (1, 2) day during pilot (P = 0.02) and 4.5 (4, 5) days (baseline) to 2 (1, 3) days (pilot) (P = 0.02) respectively. The proportion of ineligible patients stepped down to oral antibiotics was improved from 38% (baseline) to 67% (pilot). No patients failed ambulatory care requiring readmission into hospital. The ambulatory care strategy for management of NF proposed by Australian consensus guidelines has been successfully piloted at a single Victorian centre. Organisational readiness tools can be used to identify potential barriers to the implementation of evidence based practices in patients with NF.
Publisher: Wiley
Date: 26-08-2016
DOI: 10.1111/MYC.12552
Abstract: Patients undergoing allogeneic haematopoietic stem cell transplantation (alloHSCT) are at risk of developing invasive fungal infections (IFIs). Even with introduction of oral triazole antifungal agents (fluconazole, itraconazole, posaconazole and voriconazole) IFI-associated morbidity and mortality rates and economic burden remain high. Despite their proven efficacy, it is currently unknown which is the most cost-effective antifungal prophylaxis (AFP) agent. To determine the costs and outcomes associated with AFP, a decision-analytic model was used to simulate treatment in a hypothetical cohort of 1000 patients undergoing alloHSCT from the perspective of the Spanish National Health System. Generic itraconazole was the least costly AFP (€162) relative to fluconazole (€500), posaconazole oral suspension (€8628) or voriconazole (€6850). Compared with posaconazole, voriconazole was associated with the lowest number of breakthrough IFIs (36 vs 60) thus, the model predicted fewer deaths from breakthrough IFI for voriconazole (24) than posaconazole (33), and the lowest predicted costs associated with other licensed antifungal treatment and IFI treatment in a cohort of 1000. Voriconazole resulted in cost savings of €4707 per patient compared with posaconazole. Itraconazole demonstrated a high probability of being cost-effective. As primary AFP in alloHSCT patients 180 days posttransplant, voriconazole was more likely to be cost-effective than posaconazole regarding cost per additional IFI and additional death avoided.
Publisher: Oxford University Press (OUP)
Date: 18-02-2016
DOI: 10.1093/JAC/DKW008
Abstract: The presence of antimicrobial allergy designations ('labels') often substantially reduces prescribing options for affected patients, but the frequency, accuracy and impacts of such labels are unknown. The National Antimicrobial Prescribing Survey (NAPS) is an annual de-identified point prevalence audit of Australian inpatient antimicrobial prescribing using standardized definitions of guideline compliance, appropriateness and indications. Data were extracted for 2 years (2013-14) and compared for patients with an antimicrobial allergy label (AAL) and with no AAL (NAAL). Among 21 031 patients receiving antimicrobials (33 421 prescriptions), an AAL was recorded in 18%, with inappropriate antimicrobial use significantly higher in the AAL group versus the NAAL group (OR 1.12, 95% CI 1.05-1.22, P < 0.002). Patterns of antimicrobial use were significantly influenced by AAL, with lower β-lactam use (AAL versus NAAL OR 0.47, 95% CI 0.43-0.50, P < 0.001) and higher quinolone (OR 2.07, 95% CI 1.83-2.34, P < 0.0001), glycopeptide (OR 1.59, 95% CI 1.38-1.83, P < 0.0001) and carbapenem (OR 1.74, 95% CI 1.43-2.13, P < 0.0001) use. In particular, among immunocompromised patients, AAL was associated with increased rates of inappropriate antimicrobial use (OR 1.68, 95% CI 1.21-2.30, P = 0.003), as well as increased use of quinolones (OR 1.88, 95% CI 1.16-3.03, P = 0.02) and glycopeptides (OR 1.82, 95% CI 1.17-2.84, P = 0.01). AALs are common and appear to be associated with higher rates of inappropriate prescribing and increased use of broad-spectrum antimicrobials. Improved accuracy in defining AALs is likely to be important for effective antimicrobial stewardship (AMS), with efforts to 'de-label' inappropriate AAL patients a worthwhile feature of future AMS initiatives.
Publisher: Wiley
Date: 14-08-2012
DOI: 10.1111/J.1525-1446.2012.01045.X
Abstract: To investigate the health promotion and risk reduction behaviors of younger women previously treated for cancer. Guided by the "Precede-Proceed" framework, a mixed-method descriptive investigation of the health behaviors of younger women with cancer treatment-induced menopause in one health jurisdiction in Australia was undertaken. This article reports the results of the qualitative interview component of the study. Of the 85 women who responded to surveys that quantified their health behaviors, 22 consented to interviews that explored how and why these behaviors might occur. Several predisposing, enabling and reinforcing factors that influenced participants' will or ability to engage with health-promoting behaviors after cancer treatment were identified in the interviews. These include entrenched precancer diagnosis health behaviors, the disabilities resulting from cancer treatments, perceptions of risk, focused intervention by health professionals and the nature of participants' social support. The results indicate a need for flexibility when planning public health initiatives to prepare this cohort for a healthy life after cancer, which accounts for their developmental, knowledge and posttreatment needs.
Publisher: Cambridge University Press (CUP)
Date: 12-2009
DOI: 10.1086/648452
Abstract: Suspected nosocomial Aspergillus fumigatus infections in an Australian hematology unit were investigated by molecular typing of clinical and environmental isolates using polymerase chain reaction fingerprinting, CSP typing, and multilocus microsatellite typing. Only multilocus microsatellite typing revealed that all isolates were genetically distinct. The selection of an appropriate typing method is essential for effective outbreak investigations.
Publisher: Springer Science and Business Media LLC
Date: 06-2015
Publisher: Elsevier BV
Date: 08-2022
DOI: 10.1016/J.JTCT.2022.05.030
Abstract: Voriconazole (VCZ) was one of the first mold-active triazoles available however, its current use among high-risk hematology populations is unknown as the uptake of posaconazole (PCZ) and isavuconazole (ISZ) increases. We evaluated the usage and therapeutic level attainment of VCZ in hematopoietic cell transplantation (HCT) and chimeric antigen receptor T cell (CAR-T) therapy patients at our cancer center. Electronic medical records for all adult HCT or CAR-T patients with an order for VCZ, PCZ, or ISV between January 1, 2018, and June 30, 2020, were extracted. Clinical characteristics, VCZ indication, trough VCZ levels, and frequency of VCZ initiation from 6 months before to 6 months after HCT/CAR-T infusion in consecutive HCT/CAR-T recipients within the study period (infusion between July 1, 2018, and January 1, 2020) were assessed. The association between relevant clinical characteristics and the attainment of subtherapeutic or supratherapeutic levels was also evaluated. Of 468 patients prescribed mold-active triazoles, 256 (54.7%) were prescribed VCZ, 324 (69.2%) PCZ, and 60 (12.8%) ISZ 152/468 (32.5%) treatment regimens were sequentially modified to alternate mold-active triazoles. Among consecutive HCT and CAR-T recipients at our center, evaluated 6 months pre- or post- HCT/ CAR-T, VCZ was commonly initiated before or after allogeneic HCT (102/381, 26.8%), with most use in the first 30 days after stem cell infusion (40/381, 10.5%) VCZ use was less common in autologous HCT (13/276, 4.7%) and CAR-T (10/153, 6.5%). Of 223 VCZ orders that met inclusion for analysis, indications included empiric treatment in 108/223 (48.4%), directed therapy in 25/223 (11.2%), primary prophylaxis in 69/223 (30.9%) and secondary prophylaxis in 21/223 (9.4%). Of 223 eligible VCZ patients, 144 (64.6%) had at least 1 VCZ level measured during the study period 75/144 (52.1%) had a therapeutic VCZ level (1.0-5.5 mg/L) at the first measurement (median 2.8mg/L [range 0.1-13.5]) at a median of 6 days of therapy, with 26.4% subtherapeutic and 21.5% supratherapeutic 46/88 (52.3%) were therapeutic at the second measurement (2.1mg/L [0.1-9.9]) at a median of 17 days of therapy and 33/48 (68.8%) at the third (2.3mg/L [0.1-7.7]) at a median of 29 days. In multivariable analysis of factors associated with sub- or supratherapeutic levels (body mass index ≥30, concurrent omeprazole use, concurrent letermovir use, indication for VCZ, history/timeframe of HCT), the only significant association was lower odds of a supratherapeutic VCZ level among those undergoing HCT within the previous 30 days compared to those without a history of HCT. VCZ continues to remain an important option in the treatment and prevention of invasive fungal infections in an era when alternative oral mold-active triazoles are available. In spite of long-standing experience with VCZ prescribing, therapeutic level attainment remains a challenge.
Publisher: Wiley
Date: 10-2011
DOI: 10.1111/J.1445-5994.2011.02508.X
Abstract: Legionella species are a common cause of community-acquired pneumonia, infrequently complicated by cavitary disease. We describe Legionella pneumophila pneumonia and abscess formation in an immunosuppressed patient receiving corticosteroid therapy for metastatic breast carcinoma. The predisposing role of corticosteroids is discussed and the management of this complication is reviewed.
Publisher: Elsevier BV
Date: 11-2017
Publisher: Springer Science and Business Media LLC
Date: 22-02-2005
Publisher: Wiley
Date: 23-06-2013
DOI: 10.1111/TID.12106
Abstract: Cytomegalovirus (CMV) retinitis is an uncommon manifestation of CMV disease and is a marker of severe and profound immunosuppression in human immunodeficiency virus-positive patients. Here, we describe 2 cases of CMV retinitis in myeloma patients with progressive disease, following autologous stem cell transplantation and immunomodulatory therapy for myeloma. To our knowledge, this is the first report of CMV retinitis in this patient population. This report illustrates the need for close monitoring of relapsed and refractory myeloma patients for new presentations of opportunistic infections secondary to severe immunosuppression.
Publisher: Elsevier BV
Date: 07-2009
DOI: 10.1111/J.1469-0691.2009.02821.X
Abstract: The risk factors for and clinical features of bloodstream infection with uncommon Candida spp. (species other than C. albicans, C. glabrata, C. parapsilosis, C. tropicals and C. krusei) are incompletely defined. To identify clinical variables associated with these species that might guide management, 57 cases of candidaemia resulting from uncommon Candida spp. were analysed in comparison with 517 episodes of Candida albicans candidaemia (2001-2004). Infection with uncommon Candida spp. (5.3% of candidaemia cases), as compared with C. albicans candidaemia, was significantly more likely to be outpatient-acquired than inpatient-acquired (15 of 57 vs. 65 of 517 episodes, p 0.01). Prior exposure to fluconazole was uncommon (n=1). Candida dubliniensis was the commonest species (n=22, 39%), followed by Candida guilliermondii (n=11, 19%) and Candida lusitaniae (n=7, 12%).C. dubliniensis candidaemia was independently associated with recent intravenous drug use (p 0.01) and chronic liver disease (p 0.03), and infection with species other than C. dubliniensis was independently associated with age<65 years (p 0.02), male sex (p 0.03) and human immunodeficiency virus infection (p 0.05). Presence of sepsis at diagnosis and crude 30-day mortality rates were similar for C. dubliniensis-related, non-C. dubliniensis-related and C. albicans-related candidaemia. Haematological malignancy was the commonest predisposing factor in C. guilliermondii (n=3, 27%) and C. lusitaniae (n=3, 43%) candidaemia. The 30-day mortality rate of C. lusitaniae candidaemia was higher than the overall death rate for all uncommon Candida spp. (42.9% vs. 25%, p not significant). All isolates were susceptible to hotericin B, voriconazole, posaconazole, and caspofungin five strains (9%) had fluconazole MIC values of 16-32 mg/L. Candidaemia due to uncommon Candida spp. is emerging among hospital outpatients certain clinical variables may assist in recognition of this entity.
Publisher: Wiley
Date: 05-05-2014
DOI: 10.1111/TID.12223
Abstract: Prototheca species are achlorophyllus algae. Prototheca wickerhamii and Prototheca zopfii cause human disease. In immunocompetent in iduals, they cause soft tissue infections and olecranon bursitis, but in transplant recipients, these organisms can cause disseminated disease. We report a fatal case of disseminated P. zopfii infection in an hematopoietic stem cell transplant (HSCT) recipient with bloodstream infection and involvement of multiple soft tissue sites. We review all previous cases of protothecosis in HSCT reported in the literature. Protothecosis is uncommon after HSCT, but has a disseminated presentation that is frequently fatal. It is commonly misidentified as a yeast. Tumor necrosis factor-alpha inhibitors and contamination of central venous catheters may contribute to development of protothecosis. Optimal treatment approaches are yet to be defined. New agents such as miltefosine may be possible future therapies.
Publisher: Informa UK Limited
Date: 07-03-2016
DOI: 10.1586/14787210.2016.1154787
Abstract: Despite the implementation of multimodal bundles of care in hospitalised patients, post-operative sepsis in patients with cancer still accounts for a significant burden of illness and substantial healthcare costs. Patients undergoing surgery for cancer are at particular risk of sepsis due to underlying malignancy, being immunocompromised associated with cancer management and the complexity of surgical procedures performed. In this review, we evaluate the burden of illness and risks for sepsis following surgery for cancer. Current evidence supporting standardised strategies for sepsis management (including early recognition and resuscitation) is examined together with challenges in implementing quality improvement programs.
Publisher: Informa UK Limited
Date: 2002
DOI: 10.1080/10428190290006305
Abstract: We report the successful outcome of allogeneic stem cell transplant (SCT) in a patient with acute lymphoblastic leukaemia (ALL) and pulmonary zygomycosis diagnosed prior to transplant. The lesion was surgically excised and SCT proceeded with antifungal therapy, granulocyte transfusions and G-CSF support during the period of neutropenia.
Publisher: Oncology Nursing Society (ONS)
Date: 29-06-2012
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2018
Publisher: Informa UK Limited
Date: 23-04-2012
DOI: 10.3109/10428194.2012.677533
Abstract: Early and targeted antimicrobial therapy improves outcomes in patients with febrile neutropenia (FN). We evaluated the impact of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) on antimicrobial utilization in the management of FN. A cohort of patients with FN and hematological malignancy was identified. Cases (in whom FDG-PET was performed, n = 37) were compared with controls (in whom conventional investigations excluding FDG-PET were performed, n = 76). An underlying cause for FN was determined in 94.6% of cases, compared to 69.7% of controls. FDG-PET had a significant impact on antimicrobial utilization compared to conventional imaging (35.1% vs. 11.8% p = 0.003), and was associated with shorter duration of liposomal hotericin-B therapy for systemic fungal infection (median 4.0 days cases vs. 10.0 days controls p = 0.001). Cases had a longer length of hospitalization (p = 0.016). In the management of patients with high-risk FN, FDG-PET improves diagnostic yield and allows rationalization of antifungal therapy. The impact upon healthcare costs associated with antimicrobial therapy for FN requires further evaluation.
Publisher: Informa UK Limited
Date: 12-2010
DOI: 10.1586/ERP.10.69
Abstract: The incidence of invasive fungal infection has risen in recent years with the introduction of more intensive chemotherapy regimens and the advent of stem cell and solid-organ transplants. In patients undergoing chemotherapy, mortality rates ranging from 50 to 90% have been associated with documented invasive fungal infection. Voriconazole is a second-generation triazole, which is a synthesized derivative of fluconazole. It was first approved for marketing in the USA in 2002. Voriconazole has excellent bioavailability and is available in oral and intravenous dosage form. It has extended-spectrum antifungal activity whereby it is highly effective against a variety of fungal organisms, including Candida, Fusarium, Paecilomyces and Scedosporium species, but it is especially known for its activity against the Aspergillu s species. Voriconazole has become widely used for three types of treatment strategies (i.e., targeted, empirical and prophylactic). However, voriconazole is a high-cost antifungal agent and, therefore, its effectiveness should be scrutinized, taking into consideration its cost in relation to the costs of other comparable antifungal agents. This article summarizes the 18 identified peer-reviewed publications on the pharmacoeconomics of voriconazole in the English literature, up to March 2010, and provides a view on its future role in therapy. Comparisons with existing antifungals are provided when possible to illustrate the potential role of voriconazole in a clinical setting. The studies took place in a variety of countries and were all retrospective in nature, with the majority suggesting that voriconazole is a more cost-effective option for antifungal treatment. Of the 18 evaluations, 11 were related to the economic impact of voriconazole against invasive aspergillosis only. Economic data to guide the use of voriconazole as prophylaxis or empirical therapy as well as targeted therapy against invasive candidiasis remain limited.
Publisher: Informa UK Limited
Date: 28-02-2017
DOI: 10.1080/10428194.2017.1295141
Abstract: We examine the infective complications occurring during azacitidine (AZA) therapy in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). A retrospective review of patients receiving ≥1 cycle of AZA for MDS or AML was performed. Patient demographics, infection prophylaxis/episodes and outcomes were evaluated. Sixty eight patients received 884 AZA cycles. Bacterial infections occurred in 25% of cycle-1 and 27% of cycle-2 AZA therapy. Febrile neutropenia complicated 5.3% of AZA cycles, bacteremia 2% and invasive Aspergillosis 0.3%. Using Poisson modeling, a very high IPSS-R (RR 10.26, 95% CI 1.20, 87.41, p= .033) was identified as an independent risk factor for infection. Infection-related attributable mortality was 23%. The burden of infection is high in AZA-treated patients, associated with high attributable mortality. Over 25% of AZA cycles 1 and 2 were complicated by infection, predominantly bacterial, rates dropping to <10% after cycle-5.
Publisher: Wiley
Date: 06-2008
DOI: 10.1111/J.1445-5994.2008.01726.X
Abstract: Antifungal prophylaxis, empirical therapy and treatment of established fungal infections in the haematology population may be associated with significant toxicity or drug interactions leading to sub-therapeutic antifungal drug concentrations and poorer clinical outcomes. These risks may be minimised by clinical assessment, laboratory monitoring of biochemical or haematological indices, avoidance of particular drug combinations and dose modification in certain circumstances. Specific measures, such as the optimal timing of oral drug administration in relation to meals, use of pre-hydration and electrolyte supplementation may also be required. For certain agents, therapeutic drug monitoring (TDM) is warranted where non-compliance, non-linear pharmacokinetics, a narrow therapeutic window, suspected drug interaction or unexpected toxicity are encountered. Pharmacokinetics and pharmacodynamics of clinical relevance to the haematology population are discussed for the azole, polyene and echinocandin classes of antifungal agents. The evidence supporting an association between TDM and enhanced treatment outcomes is presented for in idual antifungal drugs, and recommendations for clinical practice are provided. Further randomised study of newer antifungal agents, such as posaconazole, is required to explore the potential for improved clinical outcomes in association with TDM.
Publisher: Oxford University Press (OUP)
Date: 04-03-2010
DOI: 10.1093/JAC/DKQ053
Abstract: Candidaemia in cancer patients is associated with increasing fluconazole resistance. Models for predicting such isolates and their clinical impact are required. Clinical, treatment and outcome data from a population-based candidaemia survey (2001-2004) were collected at 5 and 30 days after diagnosis. Speciation and antifungal susceptibility testing was performed. There were 138 candidaemia episodes (33% Candida albicans) in adults with haematological malignancies and 150 (51% C. albicans) in adults with solid organ malignancies. Thirty-nine isolates had fluconazole MICs of >or=64 mg/L and 40 had MICs of 16-32 mg/L (predominantly Candida glabrata and Candida krusei). By multivariate analysis, triazole therapy, gastrointestinal tract (GIT) surgery in the 30 days before candidaemia and age >65 years were predictive of fluconazole-resistant candidaemia. Thirty day crude mortality was 40% in haematology patients and 45% in oncology patients. Fluconazole-resistant isolates were associated with increased risk of mortality by univariate (P = 0.04) and Kaplan-Meier survival analyses. By Cox proportional hazards modelling, the strongest predictors of mortality at onset of candidaemia were invasive ventilation, elevated creatinine, intensive care unit (ICU) admission and receipt of systemic triazoles or corticosteroids in the previous 30 days. Removal of a central venous access device (CVAD) at or within 5 days of onset was associated with decreased mortality. Risk factors for fluconazole-resistant candidaemia in adults with cancer include fluconazole/triazole exposure and GIT surgery. ICU admission, invasive ventilation, renal impairment, age >65 years and prior exposure to corticosteroids and triazoles are risk factors for death. CVAD removal reduced mortality. These findings should be integrated into surveillance and treatment algorithms.
Publisher: Oxford University Press (OUP)
Date: 12-05-2016
DOI: 10.1093/JAC/DKW157
Abstract: The 5th European Conference on Infections in Leukaemia (ECIL-5) meeting aimed to establish evidence-based recommendations for the prophylaxis of Pneumocystis jirovecii pneumonia (PCP) in non-HIV-infected patients with an underlying haematological condition, including allogeneic HSCT recipients. Recommendations were based on the grading system of the IDSA. Trimethoprim/sulfamethoxazole given 2–3 times weekly is the drug of choice for the primary prophylaxis of PCP in adults (A-II) and children (A-I) and should be given during the entire period at risk. Recent data indicate that children may benefit equally from a once-weekly regimen (B-II). All other drugs, including pentamidine, atovaquone and dapsone, are considered second-line alternatives when trimethoprim/sulfamethoxazole is poorly tolerated or contraindicated. The main indications of PCP prophylaxis are ALL, allogeneic HSCT, treatment with alemtuzumab, fludarabine/cyclophosphamide/rituximab combinations, weeks of treatment with corticosteroids and well-defined primary immune deficiencies in children. Additional indications are proposed depending on the treatment regimen.
Publisher: Oxford University Press (OUP)
Date: 27-07-2018
DOI: 10.1093/JAC/DKY307
Publisher: Oxford University Press (OUP)
Date: 12-05-2016
DOI: 10.1093/JAC/DKW156
Abstract: The Fifth European Conference on Infections in Leukaemia (ECIL-5) convened a meeting to establish evidence-based recommendations for using tests to diagnose Pneumocystis jirovecii pneumonia (PCP) in adult patients with haematological malignancies. Immunofluorescence assays are recommended as the most sensitive microscopic method (recommendation A-II). Real-time PCR is recommended for the routine diagnosis of PCP (A-II). Bronchoalveolar lavage (BAL) fluid is recommended as the best specimen as it yields good negative predictive value (A-II). Non-invasive specimens can be suitable alternatives (B-II), acknowledging that PCP cannot be ruled out in case of a negative PCR result (A-II). Detecting β-d-glucan in serum can contribute to the diagnosis but not the follow-up of PCP (A-II). A negative serum β-d-glucan result can exclude PCP in a patient at risk (A-II), whereas a positive test result may indicate other fungal infections. Genotyping using multilocus sequence markers can be used to investigate suspected outbreaks (A-II). The routine detection of dihydropteroate synthase mutations in cases of treatment failure is not recommended (B-II) since these mutations do not affect response to high-dose co-trimoxazole. The clinical utility of these diagnostic tests for the early management of PCP should be further assessed in prospective, randomized interventional studies.
Publisher: Oxford University Press (OUP)
Date: 12-05-2016
DOI: 10.1093/JAC/DKW155
Abstract: The risk of patients with ALL and recipients of an allogeneic HSCT developing Pneumocystis jirovecii pneumonia is sufficiently high to warrant guidelines for the laboratory diagnosis, prevention and treatment of the disease. In this issue, the European Conference on Infections in Leukemia (ECIL) presents its recommendations in three companion papers.
Publisher: Springer Science and Business Media LLC
Date: 28-03-2017
Publisher: Springer Science and Business Media LLC
Date: 09-04-2014
Publisher: Oncology Nursing Society (ONS)
Date: 2005
Publisher: Oxford University Press (OUP)
Date: 29-07-2021
DOI: 10.1093/JAC/DKAB259
Abstract: To evaluate the safety and efficacy of cidofovir for the treatment of double-stranded DNA (dsDNA) viral infections following allogeneic haematopoietic cell transplant (HCT). This was a retrospective multicentre cohort study including adult HCT recipients who received ≥1 dose of IV-administered cidofovir for any dsDNA viral infection from 2006 to 2019. The objectives were to describe the rate of and risk factors for nephrotoxicity and virological response by the end of treatment (EOT). We included 165 patients from nine centres. Cidofovir was administered at 5 mg/kg/week (N = 115 69.7%), 1 mg/kg/week (18 10.9%), 3 mg/kg/week (12 7.3%) or 1 mg/kg three times/week (11 6.7%). Cidofovir was administered for adenovirus, cytomegalovirus (CMV) and BK virus infection in 75 (45.5%), 64 (38.8%) and 51 (30.9%) patients, respectively. Among 158 patients with renal function data at baseline and EOT, 40 (25.3%) developed nephrotoxicity. In multivariable analyses, age (OR 1.04 P = 0.05), weight (OR 1.05 P = 0.01), CMV infection (OR 3.6 P = 0.02), liposomal hotericin B (OR 8.06 P = 0.05) and IV voriconazole osaconazole (OR 13.0 P = 0.003) were predictors of nephrotoxicity. Creatinine concentration was significantly higher at EOT (1.16 ± 0.95 mg/dL) compared with baseline (0.91 ± 0.39 mg/dL P & 0.001), but improved by 2 weeks (0.91 ± 0.84 mg/dL P = 0.007) and 4 weeks (0.96 ± 0.89 mg/dL P = 0.03) post-EOT. Median viral load significantly declined for patients with adenovirus DNAaemia by EOT (P & 0.0001) and for patients with CMV DNAaemia by EOT + 4 weeks (P = 0.003), but not for patients with BK virus DNAaemia. One in four HCT recipients treated with IV cidofovir developed largely reversible nephrotoxicity. Careful selection of patients and close follow-up of renal function may minimize toxicity.
Publisher: Informa UK Limited
Date: 25-06-2015
Publisher: AMPCo
Date: 07-2012
DOI: 10.5694/MJA12.10466
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2010
Publisher: Wiley
Date: 14-04-2018
DOI: 10.1111/JPC.13899
Abstract: Variation in the management of fever and neutropenia (FN) in children is well described. The aim of this study was to explore the current management of FN across Australia and New Zealand and highlight areas for improvement. A practice survey was administered to paediatric health-care providers via four clinical and research networks. Using three clinical case vignettes, we explored risk stratification, empiric antibiotics, initial investigations, intravenous-oral switch, ambulatory management and antibiotic duration in children with cancer and FN. A response was received from 104 participants from 16 different hospitals. FN guideline compliance was rated as moderate or poor by 24% of respondents, and seven different fever definitions were described. There was little variation in the selected empiric monotherapy and dual-therapy regimens, and almost all respondents recommended first-dose antibiotics within 1 h. However, 27 different empiric antibiotic combinations were selected for beta-lactam allergy. An incorrect risk status was assigned to the low-risk case by 27% of respondents and to the high-risk case by 41%. Compared to current practice, significantly more respondents would manage the low-risk case in the ambulatory setting provided adequate resources were in place (43 vs. 85%, P < 0.0001). There was variation in the use of empiric glycopeptides as well as use of aminoglycosides beyond 48 h. Although the antibiotics selected for empiric management of FN are appropriate and consistent, variation and inaccuracies exist in risk stratification, the selection of monotherapy over dual therapy, empiric antibiotics chosen for beta-lactam allergy, use of glycopeptides and duration of aminoglycosides.
Publisher: Springer Science and Business Media LLC
Date: 2009
DOI: 10.1186/CC7964
Publisher: John Wiley & Sons, Ltd
Date: 07-10-2009
Publisher: Springer Science and Business Media LLC
Date: 04-1996
DOI: 10.1007/BF01695672
Abstract: Trinucleotide repeat (TNR) expansion is a kind of mutation with instability in the number of microsatellite repeats. This nature of mutation leads to the different kinds of neurological and neuromuscular disorders among them, fragile-X syndrome is the main cause of intellectual disability in which the increasing number of CGG TNR in 5' untranslated region is the main reason for epigenetic silencing of Fragile X mental retardation 1 gene. The aim of this study is to decrease the CG content of the candidate region to facilitate lification by conventional polymerase chain reaction (PCR). Bisulfite treatment of the genomic DNA results in conversion of unmethylated cytosine to uridine and may overcome the diagnostic pitfalls. The whole blood DNA was extracted and bisulfite treated. Then any simplification in PCR process of desire sequence were assayed through following conventional PCR using specifically designed primers for converted sequence. Bisulfite-treated PCR product of a nearby sequence confirmed our results as a conversion control. Both the control and the candidate sequences undergoing bisulfite treatment were successfully lified by PCR. Decreasing the GC content of the sequence by bisulfite treating could be a new approach to overcome difficulties in lifying GC-rich sequences.
Publisher: Springer Science and Business Media LLC
Date: 24-05-2004
Publisher: Wiley
Date: 15-04-2020
DOI: 10.1111/MYC.13067
Publisher: American Academy of Pediatrics (AAP)
Date: 05-2009
Abstract: OBJECTIVE. The purpose of this work was to identify differences in incidence, risk factors, microbiology, treatment, and clinical outcome of candidemia in neonates, children, and adults that might impact on management. PATIENTS AND METHODS. Cases of candidemia in Australia were identified prospectively by blood culture surveillance over 3 years. Episodes of candidemia in neonatal, pediatric, and adult age groups were analyzed and compared. RESULTS. Of 1005 incident cases, 33 occurred in neonates, 110 in children, and 862 in adults. The respective annual age-specific incidences were 4.4, 0.9, and 1.8 per 100 000 population. Prematurity and ICU admission were major risk factors in neonates. Hematologic malignancy and neutropenia were significantly more frequent in children than in neonates and adults. Diabetes, renal disease, hemodialysis, and recent surgery were more common in adults. Candidemia was attributed to a vascular access device in 58% of neonates, 70% of children, and 44% of adults. Candida albicans caused ∼48% of cases in all of the age groups. Candida parapsilosis was significantly more common in neonates and children (42% and 38% vs 15%). Candida glabrata was infrequent in neonates and children (9% and 3% vs 17%). Significantly more isolates from children were susceptible to fluconazole compared with those from adults (95% vs 75%). Fluconazole-resistant candidal isolates were infrequent in all of the age groups. Neonates and children were more likely to receive hotericin B compared with adults. Adults were more likely to receive fluconazole. Survival rates at 30 days were 78% in neonates, 90% in children, and 70% in adults. CONCLUSIONS. This study identifies significant differences in candidemia in neonates, children, and adults. Neonatologists and pediatricians must consider age-specific differences when interpreting adult studies and developing treatment and prevention guidelines.
Publisher: Oxford University Press (OUP)
Date: 03-01-2014
DOI: 10.1093/JAC/DKU529
Abstract: The clinical utility of pharmacogenomic testing in haematology patients with invasive fungal disease (IFD) receiving azole therapy has not been defined. We report our experience with CYP2C19 testing in haematological patients requiring voriconazole therapy for IFD. As a single-centre pilot study, 19 consecutive patients with a haematological malignancy undergoing active chemotherapy with a possible, probable or proven IFD requiring voriconazole therapy underwent CYP2C19 testing from 2013 to 2014. Baseline patient demographics, concurrent medications, voriconazole levels and IFD history were captured. The median voriconazole levels for intermediate metabolizer (IM) (CYP2C19*2 or 3/*1 or 17), extensive metabolizer (EM) (CYP2C19*1/*1) and heterozygote ultrarapid metabolizer (HUM)/ultrarapid metabolizer (UM) (UM, CYP2C19*17/*17 HUM, CYP2C19*1/*17) patients were 5.23, 3.3 and 1.25 mg/L, respectively. Time to therapeutic voriconazole levels was longest in the IM group, whilst voriconazole levels & mg/L were only seen in UM, HUM and EM phenotypes. The highest rates of clinical toxicity were seen in the IM group (3/5, 60%). Voriconazole exposure and toxicity was highest for IM and lowest for HUM/UM phenotypes. Time to therapeutic voriconazole level was longest in IM, whilst refractory subtherapeutic levels requiring CYP2C19 inhibition were only seen in the EM, HUM and UM phenotypes. CYP2C19 genotyping may predict those likely to have supratherapeutic or subtherapeutic levels and/or toxicity. Prospective evaluation of clinical pathways incorporating genotyping and voriconazole dose-titrating algorithms is required.
Publisher: Springer Science and Business Media LLC
Date: 06-12-2022
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2017
Publisher: Wiley
Date: 20-06-2007
DOI: 10.1111/J.1600-0609.2007.00911.X
Abstract: Vancomycin-resistant enterococci (VRE) are significant nosocomial pathogens in patients with hematologic malignancy. Identification of risk factors for infection is necessary for targeted prevention and surveillance. An outbreak of VRE infection occurred at a tertiary cancer hospital between 1 August 2003 and 30 June 2005. Infection control measures recommended by the Society for Healthcare Epidemiology of America were used throughout the outbreak period. A matched case-control study was performed to identify risk factors for VRE infection. Fourteen VRE infections (13 episodes of bacteremia, one urinary tract infection) occurred a median of 10.5 d following hospital admission. All were due to Enterococcus faecium vanB. Univariate analysis identified the following variables to be significantly associated with VRE infection: presence of neutropenia, neutropenia >or=7 d, underlying diagnosis of acute myeloid leukemia (AML), and receipt of vancomycin, metronidazole or carbapenem antibiotic therapy in the 30 d prior to infection. On multivariate analysis, an underlying diagnosis of AML [odds ratio (OR), 15.00 P = 0.017] and vancomycin therapy during the previous 30 d (OR, 17.96 P = 0.036) were retained as independent risk factors for infection. Risk stratification for development of VRE infection is possible for patients with hematologic malignancy. Patients with AML represent a high-risk population, and targeted prevention strategies must include improved antibiotic stewardship, particularly judicious use of vancomycin therapy.
Publisher: Springer Science and Business Media LLC
Date: 17-03-2015
Publisher: Informa UK Limited
Date: 15-04-2022
Publisher: Elsevier BV
Date: 08-2021
Publisher: Elsevier BV
Date: 06-2021
Publisher: Informa UK Limited
Date: 20-04-2023
Publisher: Informa UK Limited
Date: 04-2022
DOI: 10.2147/JMDH.S342197
Publisher: Wiley
Date: 27-03-2007
DOI: 10.1111/J.1439-0507.2007.01377.X
Abstract: Caspofungin (CAS) has shown efficacy as salvage monotherapy for invasive aspergillosis (IA) in two open label non-comparative trials. The association between hepatotoxicity and concomitant use of CAS and cyclosporin A (CsA) has not been fully elucidated. We report results on CAS efficacy in the first cohort from outside Europe and USA and the interaction between CAS and CsA. We retrospectively reviewed the charts of all patients with haematological malignancies or postallogeneic haematopoietic stem cell transplant (HSCT) who received >/=1 dose of CAS as salvage monotherapy for IA as part of the Australian Special Access Scheme (4/2001-8/2002). Outcomes were assessed at the end of CAS therapy. Favourable response (FR) was defined as >50% clinical and radiological improvement. Risk factors for elevation of liver transaminases (LTs) were examined using multivariate models. 54 patients were included in the analysis with 47 neutropenic at study entry. Proven or probable IA occurred in 11 and refractory IA in 28. An FR occurred in 26 (48.1%) and predictors for a poor response to CAS were allogeneic HSCT, graft vs. host disease and treatment with CAS for 7 days was an independent risk factor for laboratory hepatoxicity. The CAS efficacy results from the Australian cohort confirm those of previous studies. Close monitoring of LTs is necessary on concomitant CAS and CsA but clinically relevant hepatotoxicity is rare.
Publisher: Oxford University Press (OUP)
Date: 22-05-2013
DOI: 10.1093/CID/CIT341
Abstract: We describe antifungal therapy and management of complications due to Cryptococcus gattii infection in 86 Australian patients followed for at least 12 months. Patient data from culture-confirmed cases (2000-2007) were recorded at diagnosis, 6 weeks, 6 months, and 12 months. Clinical, laboratory, and treatment variables associated with raised intracranial pressure (ICP) and immune reconstitution inflammatory syndrome (IRIS) were determined. Seven of 10 patients with lung infection received hotericin B (AMB) induction therapy (6 with 5-flucytosine [5-FC] for a median of 2 weeks) median duration of therapy including azole eradication therapy was 41 weeks, with a complete artial clinical response in 78%. For neurologic disease, 88% of patients received AMB, 78% with 5-FC, for a median of 6 weeks. The median total course was 18 months. Nine patients receiving fluconazole induction therapy were reinduced with AMB plus 5-FC for clinical failure. Raised ICP (31 patients) was associated with initial abnormal neurology, and neurologic sequelae and/or death at 12 months (both P = .02) cerebrospinal fluid drains/shunts were placed in 58% of patients and in 64% of 22 patients with hydrocephalus. IRIS developed 2-12 months after starting antifungals in 8 patients, who presented with new/enlarging brain lesions. Risk factors included female sex, brain involvement at presentation, and higher median CD4 counts (all P < .05) corticosteroids reduced cryptococcoma-associated edema. Induction AMB plus 5-FC is indicated for C. gattii neurologic cryptococcosis (6 weeks) and when localized to lung (2 weeks). Shunting was often required to control raised ICP. IRIS presents with cerebral manifestations.
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.IJANTIMICAG.2016.07.005
Abstract: Antifungal susceptibilities of non-Aspergillus filamentous fungal pathogens cannot always be inferred from their identification. Here we determined, using the Sensititre(®) YeastOne(®) YO10 panel, the in vitro activities of nine antifungal agents against 52 clinical isolates of emergent non-Aspergillus moulds representing 17 fungal groups in Australia. Isolates comprised Mucorales (n = 14), Scedosporium/Lomentospora spp. (n = 18) and a range of hyaline hyphomycetes (n = 9) and other dematiaceous fungi (n = 11). Excluding Verruconis gallopava, echinocandins demonstrated poor activity (MICs generally >8 mg/L) against these moulds. Lomentospora prolificans (n = 4) and Fusarium spp. (n = 6) demonstrated raised MICs to all antifungal drugs tested, with the lowest being to voriconazole and hotericin B (AmB), respectively (geometric mean MICs of 3.4 mg/L and 2.2 mg/L, respectively). All Scedosporium apiospermum complex isolates (n = 14) were inhibited by voriconazole concentrations of ≤0.25 mg/L, followed by posaconazole and itraconazole at ≤1 mg/L. Posaconazole and AmB were the most active agents against the Mucorales, with MIC90 values of 1 mg/L and 2 mg/L, respectively, for Rhizopus spp. For dematiaceous fungi, all isolates were inhibited by itraconazole and posaconazole concentrations of ≤0.5 mg/L (MIC90, 0.12 mg/L and 0.25 mg/L, respectively), but voriconazole and AmB also had in vitro activity (MIC90, 0.5 mg/L and 1 mg/L, respectively). Differences in antifungal susceptibility within species and between species within genera support the need for testing in idual patient isolates to guide therapy. The Sensititre(®) YeastOne(®) offers a practical alternative to the reference methodology for susceptibility testing of moulds.
Publisher: Wiley
Date: 04-2004
Publisher: Elsevier BV
Date: 03-2014
DOI: 10.1016/J.BLRE.2014.01.004
Abstract: Plasma cell myeloma (PCM) is increasing in prevalence in older age groups and infective complications are a leading cause of mortality. Patients with PCM are at increased risk of severe infections, having deficits in many arms of the immune system due to disease and treatment-related factors. Treatment of PCM has evolved over time with significant impacts on immune function resulting in changing rates and pattern of infection. Recently, there has been a paradigm shift in the treatment of PCM with the use of immunomodulatory drugs and proteasome inhibitors becoming the standard of care. These drugs have wide-ranging effects on the immune system but their impact on infection risk and aetiology remain unclear. The aims of this review are to discuss the impact of patient, disease and treatment factors on immune function over time for patients with PCM and to correlate immune deficits with the incidence and aetiology of infections seen clinically in these patients. Preventative measures and the need for clinically relevant tools to enable infective profiling of patients with PCM are discussed.
Publisher: Wiley
Date: 24-06-2015
DOI: 10.1111/BJH.13532
Abstract: We defined the epidemiology and clinical predictors of infection in patients with multiple myeloma (MM) receiving immunomodulatory drugs (IMiDs), proteasome inhibitors (PI) and autologous haematopoietic stem cell transplant (ASCT) in a large longitudinal cohort study. Clinical and microbiology records of patients with MM diagnosed between January 2008 and December 2012 were reviewed to capture patient demographics, characteristics of myeloma and infections (type, severity, outcomes). Conditional risk set modelling was used to determine clinical predictors of infection. One hundred and ninety-nine patients with MM with 771 episodes of infection were identified. 44·6% of infections were clinically defined, 35·5% were microbiologically defined and 19·9% were fever of unknown focus. There was a bimodal peak in incidence of bacterial (4-6 and 70-72 months) and viral infections (7-9 and 52-54 months) following disease diagnosis. Chemotherapy regimens high-dose melphalan [hazard ratio (HR) = 2·07], intravenous cyclophosphamide (HR = 1·96) and intensive combination systemic chemotherapy (HR = 1·86) and cumulative doses of corticosteroid (HR = 3·06 at highest dose) were independently associated with increased risk of infection overall (P < 0·05). IMiDs and PI and other clinical factors were not independently associated with increased risk of infection. New approaches to prevention and treatment of infection should focus upon identified periods of risk and treatment-related risk factors.
Publisher: Springer Science and Business Media LLC
Date: 28-05-2014
Publisher: Springer Science and Business Media LLC
Date: 14-09-2018
Publisher: Springer Science and Business Media LLC
Date: 12-07-2004
Publisher: AMPCo
Date: 11-2014
DOI: 10.5694/MJA13.00214
Publisher: Wiley
Date: 11-12-2021
DOI: 10.1111/MYC.13211
Publisher: Georg Thieme Verlag KG
Date: 12-2011
Abstract: Invasive mold infections affecting the lungs are increasing in incidence and ersity. Severely immunocompromised patients are particularly vulnerable to infection from unusual, normally nonpathogenic fungi that are found naturally in the environment. Certain fungi such as Scedosporium and the dematiaceous fungi also cause lung disease in hosts without overt immune compromise. The impacts of these emerging pathogens range from airway colonization to locally invasive lung, and disseminated, disease. Diagnosis requires isolation and identification of the etiologic agent by either or both phenotypic and molecular biology methods. Evidence of tissue invasion on histopathology is often required to distinguish infection from colonization. Diagnostic imaging techniques are nonspecific, and there are no reliable serological biomarkers of infection. Many rare molds and yeasts demonstrate reduced in vitro susceptibility to antifungal agents. Although hotericin B formulations remain clinically useful for many of these infections, voriconazole and posaconazole are more effective for some of these difficult-to-treat pathogens. Surgical resection of diseased tissue and support of the host immune system are often required to optimize outcomes.
Publisher: Springer Science and Business Media LLC
Date: 10-12-2014
Publisher: Springer Science and Business Media LLC
Date: 12-12-2012
Publisher: MyJove Corporation
Date: 28-12-2017
DOI: 10.3791/56714
Publisher: Wiley
Date: 06-2008
DOI: 10.1111/J.1445-5994.2008.01727.X
Abstract: Hospital building works increase the risk of invasive fungal infections. Nosocomial outbreaks have been reported. A pre-emptive strategy for planned building works is paramount. The roles of HEPA filtration, air-s ling and modulation of 'routine' antifungal prophylaxis practice are discussed in the context of pre-emptive planning and outbreak management.
Publisher: Wiley
Date: 07-2015
Publisher: Wiley
Date: 20-01-2015
DOI: 10.1111/BCP.12310
Publisher: Wiley
Date: 25-11-2006
DOI: 10.1111/J.1365-2141.2005.05789.X
Abstract: There is an increasing use of monoclonal antibodies in the treatment of haematological malignancies. Alemtuzumab (C ath-1H Ilex Pharmaceuticals, San Antonio, TX, USA) is a monoclonal antibody reactive with the CD52 antigen used as first and second line therapy for two types of lymphoproliferative disorders: chronic lymphocytic leukaemia (CLL), and T-cell lymphomas [both peripheral (PTCL) and cutaneous (CTCL)]. With alemtuzumab therapy, viral, bacterial and fungal infectious complications are frequent, and may be life threatening. An understanding of the patients at highest risk and duration of risk are important in developing recommendations for empirical management, antimicrobial prophylaxis and targeted surveillance. This review discusses the infection risks associated with these lymphoproliferative disorders and their treatment, and provide detailed recommendations for screening and prophylaxis.
Publisher: Oxford University Press (OUP)
Date: 17-03-2010
DOI: 10.1093/JAC/DKQ076
Abstract: Voriconazole and posaconazole are used prophylactically against invasive fungal infection (IFI) in patients with acute myeloid leukaemia (AML). The current study attempted to evaluate the economics of voriconazole versus posaconazole for prophylaxis in AML. A 6 year (2003-09) retrospective chart review of AML patients was performed at a major Australian tertiary hospital. Patients were followed through the induction stage of chemotherapy, estimating outcome probabilities and prescribing patterns of antifungal prophylaxis. Cost inputs were obtained from the latest Australian sources. A decision analytical model was developed to depict options and consequences involved in the prophylaxis, including success, survival, possible and proven IFIs, and discontinuations due to intolerance. A cost-benefit analysis and an uncertainty study through sensitivity analyses were performed. Fifty-six and 38 patients were evaluated in the voriconazole and posaconazole groups, respectively. Baseline demographic characteristics were not significantly different between the study cohorts. Posaconazole was associated with an overall cost saving of AU$17,458 (29%) per patient over voriconazole. The posaconazole group was associated with lower rate of death, as well as lower probability of discontinuation because of possible infections and intolerance to oral administration. The voriconazole group was associated with fewer proven infections. As per sensitivity analyses, results were highly robust over variations in all costs and probabilities in the model. Monte Carlo simulation suggested a 91.6% chance for posaconazole to cost less than voriconazole. This is the first economic evaluation of voriconazole versus posaconazole where posaconazole appears to be more cost-beneficial than voriconazole as antifungal prophylaxis in AML.
Publisher: Informa UK Limited
Date: 31-12-2013
Publisher: Informa UK Limited
Date: 02-2011
DOI: 10.3109/10428194.2010.542600
Abstract: Invasive aspergillosis (IA) is a major cause of mortality in patients with hematological malignancies, due largely to the inability of traditional culture and biopsy methods to make an early or accurate diagnosis. Diagnostic accuracy studies suggest that Aspergillus galactomannan (GM) enzyme immunoassay (ELISA) and Aspergillus PCR-based methods may overcome these limitations, but their impact on patient outcomes should be evaluated in a diagnostic randomized controlled trial (D-RCT). This article describes the methodology of a D-RCT which compares a new pre-emptive strategy (GM-ELISA- and Aspergillus PCR-driven antifungal therapy) with the standard fever-driven empiric antifungal treatment strategy. Issues including primary end-point and patient selection, duration of screening, choice of tests for the pre-emptive strategy, antifungal prophylaxis and bias control, which were considered in the design of the trial, are discussed. We suggest that the template presented herein is considered by researchers when evaluating the utility of new diagnostic tests (ClinicalTrials.gov number, NCT00163722).
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2012
Publisher: Wiley
Date: 2011
DOI: 10.1111/J.1445-5994.2010.02342.X
Abstract: An abundance of new evidence regarding treatment strategies for neutropenic fever is likely to contribute to variability in practice across institutions and clinicians alike. To describe current clinical practices in Australia, by surveying haematologists, oncologists and infectious diseases physicians involved in cancer care. Clinician members from Australian professional associations, accounting for the vast majority of Australian cancer specialists, were invited to participate in an electronic survey, comprising of a clinical case-based questionnaire. Clinical practice areas explored were: use of risk-assessment and empiric antibiotic strategies across various treatment settings use of anti-bacterial prophylaxis and use of granulocyte-colony stimulating factors for established neutropenic fever and for secondary prophylaxis. A total of 252 clinicians returned responses (approximately 30% response rate). The majority (>70%) were representative of practices in public, major city, tertiary referral hospitals. Less than half of clinicians were aware of risk-assessment tools and less than quarter currently used ambulatory care strategies. If adequate resources were made available, more than 80% were willing to use risk-assessment tools and 60% more clinicians were likely to use ambulatory care strategies. Most clinicians prescribed dual therapy parenteral antibiotics, even for clinically stable patients (53% haematologists, 56% oncologists). Granulocyte-colony stimulating factor was used frequently as secondary prophylaxis in the breast cancer case (91%), follicular lymphoma case (59%) and non-small cell lung cancer case (31%). Fluoroquinolone prophylaxis was infrequently prescribed (19% oncologists, 30% haematologists). Evidence-practice gaps were identified around the use of risk-assessment-based empiric therapy, and help to inform better clinical guidance.
Publisher: Elsevier BV
Date: 09-2017
DOI: 10.1016/J.CMI.2017.03.014
Abstract: Multi-antifungal drug resistance in Candida glabrata is increasing. We examined the feasibility of next-generation sequencing (NGS) to investigate the presence of antifungal drug resistance markers in C. glabrata. The antifungal susceptibility of 12 clinical isolates and one ATCC strain of C. glabrata was determined using the Sensititre YeastOne High-quality non-synonymous SNPs in antifungal resistance genes such as FKS1, FKS2, CgCDR1, CgPDR1 and FCY2 were identified. For two of three isolate pairs, there was a >60-fold rise in MICs to all echinocandins in the second isolate from each pair one echinocandin-resistant isolate harboured a mutation in FKS1 (S629P) and the other in FKS2 (S663P). Of the third pair, both the 5-fluorocytosine-susceptible, and resistant isolates had a mutation in FCY2 (A237T). SNPs in CgPDR1 were found in pan-azole-resistant isolates. SNPs in other genes linked to azole resistance (CgCDR1, ERG9 and CgFLR1) were present in both azole-susceptible and azole-resistant isolates. SNPs were also identified in Candida adhesin genes EPA1, EPA6, PWP2 and PWP5 but their presence was not associated with higher drug MICs. Genome-wide analysis of antifungal resistance markers was feasible and simultaneously revealed mutation patterns of genes implicated in resistance to different antifungal drug classes.
Publisher: Springer Science and Business Media LLC
Date: 08-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-1994
DOI: 10.1097/00007890-199410270-00010
Abstract: Bronchoalveolar lavage (BAL) was performed between days 35 and 45 posttransplant in 37 marrow recipients without clinical or radiologic evidence of cytomegalovirus (CMV) pneumonia to determine if the presence of CMV or cellular characteristics was predictive of subsequent development of CMV pneumonia. Analysis of BAL fluid included culture and direct fluorescent antibody staining for CMV, total mononuclear cell count, lymphocyte count, and lymphocyte subsets. Patients were followed to day 110 after transplant for development of CMV pneumonia. Weekly cultures of blood, urine, and throat were also obtained. BAL was positive for CMV in 7 patients, of whom 3 developed CMV pneumonia. It was negative for CMV in 30 patients, of whom 7 developed CMV pneumonia. The positive and negative predictive values for detection of CMV in day 35-45 BAL were 43% and 78%, for CMV viremia 66% and 87%, and for detection of CMV in urine and throat 41% and 94%, respectively, for subsequent CMV pneumonia. In 9/10 patients who subsequently developed CMV pneumonia, excretion of CMV from BAL, blood, urine or throat preceded CMV pneumonia, and BAL was the earliest site of CMV excretion in all nine. Only one patient did not excrete before developing CMV pneumonia. In a stepwise logistic regression of risk factors for developing CMV pneumonia, only CMV viremia was significant (P = 0.002) although the total BAL mononuclear cell count approached significance (P = 0.053). The percentage of lymphocytes in BAL and CMV excretion in BAL, urine, and throat were not significant. The positive predictive value of BAL for subsequent CMV pneumonia was no greater than that of culture of urine and throat and less than that of viremia in our patients.
Publisher: Informa UK Limited
Date: 02-01-2013
Publisher: Informa UK Limited
Date: 02-01-2019
Publisher: Informa UK Limited
Date: 19-07-2020
Publisher: Wiley
Date: 07-2002
DOI: 10.1034/J.1600-0609.2002.02745.X
Abstract: The potential for life-threatening pneumonia due to respiratory syncytial virus (RSV) infection is recognised among patients with acute leukaemia and recipients of allogeneic or autologous bone marrow transplantation. RSV pneumonia has a high mortality rate in these settings. Less intensively treated patients are not usually considered to be at risk for serious RSV pneumonia. We describe the case of a 62-yr-old patient with chronic lymphocytic leukaemia (CLL) treated with fludarabine and cyclophosphamide who developed severe RSV pneumonia and recovered following treatment including intravenous ribavirin.
Publisher: ACM
Date: 26-11-2012
Publisher: Informa UK Limited
Date: 02-01-2013
Publisher: Informa UK Limited
Date: 28-04-2016
Publisher: Ferrata Storti Foundation (Haematologica)
Date: 10-10-2014
Publisher: Elsevier BV
Date: 02-2003
Publisher: Elsevier BV
Date: 09-2023
Publisher: Springer Science and Business Media LLC
Date: 2011
DOI: 10.2165/11585270-000000000-00000
Abstract: This review compares the pharmacology, spectrum of antifungal activity, pharmacokinetic and pharmacodynamic properties, safety and clinical efficacy of the three licensed echinocandins: caspofungin, micafungin and anidulafungin. Echinocandins inhibit the synthesis of 1,3-β-D-glucan, an essential component of the fungal cell wall, and represent a valuable treatment option for fungal infections. The echinocandins exhibit potent in vitro and in vivo fungicidal activity against Candida species, including azole-resistant pathogens. For all agents, strains with drug minimum inhibitory concentrations (MICs) of ≤ 2 μg/mL are considered susceptible the MIC at which 90% of isolates tested were inhibited (MIC₉₀) values are typically 2 μg/mL. Of the three echinocandins, the in vitro 'paradoxical effect' (increased growth at supra-MIC drug concentrations) is observed least often with anidulafungin. All echinocandins have low oral bioavailability, and distribute well into tissues, but poorly into the CNS and eye. Anidulafungin is unique in that it undergoes elimination by chemical degradation in bile rather than via hepatic metabolism, has a lower maximum concentration and smaller steady state under the concentration-time curve but longer half-life than caspofungin or micafungin. In children, dosing should be based on body surface area. Daily doses of caspofungin (but not micafungin and anidulafungin) should be decreased (from 50 to 35 mg) in moderate liver insufficiency. All echinocandins display concentration-dependent fungicidal (for Candida) or fungistatic (for Aspergillus) activity. The postantifungal effect is 0.9-20 hours against Candida and <0.5 hours against Aspergillus. The echinocandins are well tolerated with few serious drug-drug interactions since they are not appreciable substrates, inhibitors or inducers of the cytochrome P450 or P-glycoprotein systems. In parallel with the greater clinical experience with caspofungin, this agent has a slightly higher potential for adverse effects/drug-drug interactions, with the least potential observed for anidulafungin. Caspofungin (but not micafungin or anidulafungin) dosing should be increased if coadministered with rif icin and there are modest interactions of caspofungin with calcineurin inhibitors. All three agents are approved for the treatment of oesophageal candidiasis, candidaemia and other select forms of invasive candidiasis. Only micafungin is licensed for antifungal prophylaxis in stem cell transplantation, whereas caspofungin is approved for empirical therapy of febrile neutropenia. Caspofungin has been evaluated in the salvage and primary therapy of invasive aspergillosis. Combination regimens incorporating an echinocandin showing promise in the treatment of aspergillosis. However, echinocandins remain expensive to use.
Publisher: Springer Science and Business Media LLC
Date: 02-02-2017
DOI: 10.1007/S00520-017-3606-Y
Abstract: Clostridium difficile infection (CDI) is the leading cause of diarrhoea in hospitalised patients. Cancer populations are at high-risk for infection, but comprehensive evaluation in the current era of cancer care has not been performed. The objective of this study was to describe characteristics, risk factors, and outcomes of CDI in cancer patients. Fifty consecutive patients with CDI at a large Australian cancer centre (2013-2015) were identified from the hospital pathology database. Each case was matched by ward and hospital admission date to three controls without toxigenic CDI. Treatment and outcomes of infection were evaluated and potential risk factors were analysed using conditional logistic regression. Patients with CDI had a mean age of 59.7 years and 74% had an underlying solid tumour. Healthcare-associated infection comprised 80% of cases. Recurrence occurred in 10, and 12% of cases were admitted to ICU within 30 days. Severe or severe-complicated infection was observed in 32%. Independent risk factors for infection included chemotherapy (odds ratio (OR) 3.82, 95% CI 1.67-8.75 p = 0.002), gastro-intestinal/abdominal surgery (OR 4.64, 95% CI 1.20-17.91 p = 0.03), proton pump inhibitor (PPI) therapy (OR 2.47, 95% CI 1.05-5.80 p = 0.04), and days of antibiotic therapy (OR 1.04, 95% CI 1.01-1.08 p = 0.02). Severe or complicated infections are frequent in patients with cancer who develop CDI. Receipt of chemotherapy, gastro-intestinal/abdominal surgery, PPI therapy, and antibiotic exposure contribute to infection risk. More effective CDI therapy for cancer patients is required and dedicated antibiotic stewardship programs in high-risk cancer populations are needed to ameliorate infection risk.
Publisher: Oxford University Press (OUP)
Date: 28-02-2014
DOI: 10.1093/MMY/MYT020
Abstract: Pneumocystis jirovecii pneumonia (PJP) is increasingly seen in association with the use of new and potent immunosuppressive therapies in populations not infected with human immunodeficiency virus. Today, molecular methods are widely used to improve diagnostic yield however, the relationship between clinical findings and quantitative polymerase chain reaction (qPCR) results is undefined. Our objective was to describe characteristics of PJP in patients with malignancies and determine if qPCR results were correlated with clinical findings. From 2007 to 2012, all patients at the Peter MacCallum Cancer Centre with positive Pneumocystis PCR were identified from a microbiology database. Clinical, radiological, and microbiological records were reviewed. PJP was defined as the presence of positive PCR for Pneumocystis on a respiratory specimen, radiological abnormalities consistent with a pneumonic process, and receipt of targeted PJP treatment. qPCR was performed on all diagnostic specimens, and values were reported according to clinical findings. Forty-five patients fulfilled inclusion criteria: 44.4% had underlying solid organ tumors and 55.6% had hematological malignancies. Nonsmall cell lung carcinoma and lymphoma were the most frequent predispositions. Shortness of breath, cough, and fever were reported in 64.4%, 48.9%, and 42.2% of the patients, respectively. Admission to the intensive care unit and mortality rates were lower than in previous reports. Overall, a relationship between other clinical features and qPCR results was not identified. In the era of routine molecular diagnostics, patients with malignancy and PJP have improved outcomes. However, there was no demonstrable relationship between qPCR results and clinical features or PCR data and outcomes.
Publisher: Wiley
Date: 06-2003
Publisher: Elsevier BV
Date: 11-2018
DOI: 10.1016/J.BLRE.2018.04.007
Abstract: Chronic lymphocytic leukaemia (CLL) is the most common leukaemia with infections a leading cause of morbidity and mortality. Recently there has been a paradigm shift from the use of chemo-immunotherapies to agents targeting specific B-lymphocyte pathways. These agents include ibrutinib, idelalisib and venetoclax. In this review, the risks and timing of infections associated with these agents are described, taking into account disease and treatment status. Treatment with ibrutinib as monotherapy or in combination with chemo-immunotherapies is not associated with additional risk for infection. In contrast, the use of idelalisib is associated with a 2-fold risk for severe infection and opportunistic infections. Venetoclax does not appear to be associated with additional infection risk. The evolving spectrum of pathogens responsible infections in CLL patients, especially those with relapsed and refractory disease are described, and prevention strategies (prophylaxis, monitoring and vaccination) are proposed.
Publisher: Elsevier BV
Date: 06-2013
Publisher: Elsevier BV
Date: 2003
Publisher: Elsevier BV
Date: 2018
DOI: 10.1016/J.JINF.2017.10.009
Abstract: Fluoroquinolone (FQ) prophylaxis was recommended in 2005 by European Conference on Infections in Leukemia (ECIL) for patients with prolonged neutropenia. In consideration of a worldwide increase in antibiotic resistance, the issue of FQ prophylaxis during neutropenia was re-evaluated. Literature review of randomised controlled trials (RCT) and observational studies published in years 2006-2014 was performed. Their results were analysed in meta-analysis. Meta-regression model was applied to evaluate whether the rates of FQ resistance in community and hospital settings influenced the efficacy of FQ prophylaxis. The impact of FQ prophylaxis on colonisation and infection with resistant bacteria was reviewed. Two RCTs and 12 observational studies were identified. FQ prophylaxis did not have effect on mortality (pooled OR 1.01, 95%CI 0.73-1.41), but was associated with lower rate of bloodstream infections (BSI) (pooled OR 0.57, 95%CI 0.43-0.74) and episodes of fever during neutropenia (pooled OR 0.32, 95%CI 0.20-0.50). No effect of the background rate of FQ resistance on the efficacy of FQ prophylaxis was observed. In few studies, FQ prophylaxis resulted in an increased colonisation or infection with FQ- or multi-drug resistant strains. The possible benefits of FQ prophylaxis on BSI rate, but not on overall mortality, should be weighed against its impact in terms of toxicity and changes in local ecology in single centres.
Publisher: Springer Science and Business Media LLC
Date: 18-03-2020
DOI: 10.1186/S12879-020-04952-5
Abstract: Vancomycin-resistant enterococcus (VRE) is an important cause of infection in immunocompromised populations. Few studies have described the characteristics of vanB VRE infection. We sought to describe the epidemiology, treatment and outcomes of VRE bloodstream infections (BSI) in a vanB predominant setting in malignant hematology and oncology patients. A retrospective review was performed at two large Australian centres and spanning a 6-year period (2008–2014). Evaluable outcomes were intensive care admission (ICU) within 48 h of BSI, all-cause mortality (7 and 30 days) and length of admission. Overall, 106 BSI episodes were observed in 96 patients, predominantly Enterococcus faecium vanB (105/106, 99%). Antibiotics were administered for a median of 17 days prior to BSI, and 76/96 (79%) were neutropenic at BSI onset. Of patients screened before BSI onset, 49/72 (68%) were found to be colonised. Treatment included teicoplanin (59), linezolid (6), daptomycin (2) and sequential/multiple agents (21). Mortality at 30-days was 31%. On multivariable analysis, teicoplanin was not associated with mortality at 30 days. VRE BSI in a vanB endemic setting occurred in the context of substantive prior antibiotic use and was associated with high 30-day mortality. Targeted screening identified 68% to be colonised prior to BSI. Teicoplanin therapy was not associated with poorer outcomes and warrants further study for vanB VRE BSI in cancer populations.
Publisher: Elsevier BV
Date: 07-2021
DOI: 10.1016/J.CLML.2021.02.002
Abstract: Treatment for multiple myeloma (MM) has continued to evolve with second generation immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and monoclonal antibodies (mAbs). This study aims to evaluate the epidemiology and risks of infection in patients with MM managed with these therapies. Clinical and microbiological records were reviewed to capture patient demographics, disease characteristics, treatment received, episodes of infection, and outcomes. Infections were classified as microbiologically defined (MDI), clinically defined (CDI), and fever of unknown focus (FUF). Univariate and multivariate analyses were performed to determine risk factors for infection, with a P value 4) (OR, 7.72 95% CI, 1.25-47.81) were associated with increased risk of infection (all P 4) were associated with higher risk for infection.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2014
Publisher: Informa UK Limited
Date: 31-12-2020
Publisher: Cambridge University Press (CUP)
Date: 10-2008
DOI: 10.1086/591938
Publisher: Elsevier BV
Date: 11-2017
Publisher: SAGE Publications
Date: 10-2007
Abstract: Despite the volume of biomedical and psychosocial discourse surrounding both renal transplantation and the immune system, there is a limit to current understandings of immunosuppression in the context of kidney transplantation. For ex le, we do not know how the immunosuppressed renal transplant recipient experiences and understands their immune system and body. In addition, we do not know if the patient is as fixated on `graft survival' as their healthcare team or whether other concerns are more relevant. What is missing is the discourse of those who actually `live' the medically altered immune system in the context of renal transplantation. We propose that this gap in knowledge is bound to an acknowledged problem among renal transplant recipients and their healthcare teams — a lack of compliance with recommended medical regimens. Our argument here is that an exploration of patient intimacy with transplant-related immunosuppression might illuminate a different understanding of this experience that could enhance health professionals' understanding and their subsequent approach to treatment. We contend that the embodied and contextual experience of the patient needs to be equally valued in order to enhance patient outcomes.
Publisher: Springer Science and Business Media LLC
Date: 22-12-2013
DOI: 10.1007/S00520-013-2095-X
Abstract: This study investigated the efficacy and safety of cryotherapy, in the form of frozen gel gloves, in relation to docetaxel-induced hand and fingernail toxicities. After piloting with 21 patients, a consecutive series s le of patients (n=53) prescribed docetaxel every 3 weeks, for a minimum of three cycles, was enrolled in this randomised control trial. Participants acted as their own control, with the frozen gel glove worn on one randomised hand for 15 min prior to infusion, for the duration of the infusion, and for 15 min of after completion of treatment. Hand and nail toxicities were evaluated by two blinded assessors according to CTCAE.v4 criteria. To assess the potential for cross-infection of multi-use gloves, microbial culture and sensitivity swabs were taken of each glove at every tenth use. Of the 53 participants enrolled in the main study, 21 provided evaluable data. There was a 60 % withdrawal rate due to patient discomfort with the intervention. The mean incidence and severity of toxicities in all evaluable cycles in control and intervention hands respectively were erythroderma grade 1 (5/5 %), nail discolouration grade 1 (81/67 %), nail loss grade 1 (19/19 %) and nail ridging grade 1 (57/57 %). No significant differences were determined between hand conditions in terms of time to event, nor in terms of toxicity in gloved and non-gloved hands. While cryotherapy in the form of frozen gloves for the cutaneous toxicities associated with docetaxel is safe, its limited efficacy, patient discomfort and some logistical issues preclude its use in our clinical setting.
Publisher: Springer Science and Business Media LLC
Date: 20-03-2014
DOI: 10.1007/S00520-014-2210-7
Abstract: Paper-based nutrition screening tools can be challenging to implement in the ambulatory oncology setting. The aim of this study was to determine the validity of the Malnutrition Screening Tool (MST) and a novel, automated nutrition screening system compared to a 'gold standard' full nutrition assessment using the Patient-Generated Subjective Global Assessment (PG-SGA). An observational, cross-sectional study was conducted in an outpatient oncology day treatment unit (ODTU) within an Australian tertiary health service. Eligibility criteria were as follows: ≥ 18 years, receiving outpatient anticancer treatment and English literate. Patients self-administered the MST. A dietitian assessed nutritional status using the PG-SGA, blinded to the MST score. Automated screening system data were extracted from an electronic oncology prescribing system. This system used weight loss over 3 to 6 weeks prior to the most recent weight record or age-categorised body mass index (BMI) to identify nutritional risk. Sensitivity and specificity against PG-SGA (malnutrition) were calculated using contingency tables and receiver operating curves. There were a total of 300 oncology outpatients (51.7% male, 58.6 ± 13.3 years). The area under the curve (AUC) for weight loss alone was 0.69 with a cut-off value of ≥ 1% weight loss yielding 63% sensitivity and 76.7% specificity. MST (score ≥ 2) resulted in 70.6% sensitivity and 69.5% specificity, AUC 0.77. Both the MST and the automated method fell short of the accepted professional standard for sensitivity (~≥ 80%) derived from the PG-SGA. Further investigation into other automated nutrition screening options and the most appropriate parameters available electronically is warranted to support targeted service provision.
Publisher: Wiley
Date: 02-05-2017
DOI: 10.1002/JPPR.1234
Publisher: Cambridge University Press (CUP)
Date: 02-2021
Abstract: To compare antimicrobial prescribing practices in Australian hematology and oncology patients to noncancer acute inpatients and to identify targets for stewardship interventions. Retrospective comparative analysis of a national prospectively collected database. Using data from the 2014–2018 annual Australian point-prevalence surveys of antimicrobial prescribing in hospitalized patients (ie, Hospital National Antimicrobial Prescribing Survey called Hospital NAPS), the most frequently used antimicrobials, their appropriateness, and guideline concordance were compared among hematology/bone marrow transplant (hemBMT), oncology, and noncancer inpatients in the setting of treatment of neutropenic fever and antibacterial and antifungal prophylaxis. In 454 facilities, 94,226 antibiotic prescriptions for 62,607 adult inpatients (2,230 hemBMT, 1,824 oncology, and 58,553 noncancer) were analyzed. Appropriateness was high for neutropenic fever management across groups (83.4%–90.4%) however, hemBMT patients had high rates of carbapenem use (111 of 746 prescriptions, 14.9%), and 20.2% of these prescriptions were deemed inappropriate. Logistic regression demonstrated that hemBMT patients were more likely to receive appropriate antifungal prophylaxis compared to oncology and noncancer patients (adjusted OR, 5.3 P .001 for hemBMT compared to noncancer patients). Oncology had a low rate of antifungal prophylaxis guideline compliance (67.2%), and incorrect dosage and frequency were key factors. Compared to oncology patients, hemBMT patients were more likely to receive appropriate nonsurgical antibacterial prophylaxis (aOR, 8.4 95% CI, 5.3–13.3 P .001). HemBMT patients were also more likely to receive appropriate nonsurgical antibacterial prophylaxis compared to noncancer patients (OR, 3.1 95% CI, 1.9–5.0 P .001). However, in the Australian context, the hemBMT group had higher than expected use of fluoroquinolone prophylaxis (66 of 831 prescriptions, 8%). This study demonstrates why separate analysis of hemBMT and oncology populations is necessary to identify specific opportunities for quality improvement in each patient group.
Publisher: Wiley
Date: 29-02-2020
DOI: 10.1111/TID.13260
Publisher: Oxford University Press (OUP)
Date: 2012
DOI: 10.3109/13693786.2011.602989
Abstract: With more than half the world's population, many Asia-Pacific countries still lack resources for adequate infection control and diagnostics. Opportunistic invasive fungal infections (IFIs) have a significant impact on public health in the region, and early diagnosis and appropriate treatment remain important. The incidence of IFI in the Asia-Pacific region is increasing because of the expanded population of immunosuppressed patients resulting from advances in medical technology, such as treatments for cancer and transplantation, as well as the impact of human immunodeficiency virus. Even so, the epidemiology of IFIs is not well described in the Asia-Pacific region. Prevalence of some infections, such as mucormycosis, is particularly related to undiagnosed or untreated diabetes, which is likely to be a continuing problem with the epidemic of diabetes in the region. In addition, despite some effective treatment options, IFIs are associated with high morbidity and mortality. In an attempt to increase recognition of invasive mycoses in this large area, this paper reviews recent findings on the epidemiology of the most clinically significant opportunistic mould and yeast infections in the Asia-Pacific region, i.e., aspergillosis, mucormycosis, pythiosis, scedosporiosis, fusariosis, candidiasis, trichosporonosis, and cryptococcosis.
Publisher: Elsevier BV
Date: 09-2014
DOI: 10.1016/J.JHIN.2014.06.007
Abstract: The effectiveness of ethanol locks for prevention of central venous catheter (CVC)-associated bloodstream infection (CLABSI) in adult haematology patients has not been thoroughly evaluated. This study aimed to compare prospectively heparinized saline with 70% ethanol locks using 2 h dwell time in patients with tunnelled CVCs. In saline (N = 43) and ethanol (N = 42) groups, CLABSI rates were 6.0 [95% confidence interval (CI): 3.4-9.8] and 4.1 (95% CI: 1.9-7.7) per 1000 CVC days, respectively (P = 0.42). In the ethanol group, two exit-site infections and one tunnel ocket infection were observed. Reduction in device-associated infection was not achieved with prophylactic 70% ethanol locks in patients with haematological malignancy and tunnelled CVCs.
Publisher: AMPCo
Date: 06-2018
DOI: 10.5694/MJA17.00487
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 08-2007
Publisher: Informa UK Limited
Date: 15-07-2014
Publisher: SAGE Publications
Date: 05-2016
DOI: 10.5301/JVA.5000509
Abstract: To reduce the risk of infections associated with indwelling central venous catheters (CVCs), practices for hub disinfection have been widely promoted. The objective of this study was to design and implement a standardised tool to monitor compliance with 'scrub the hub' practices at an Australian centre. Review of existing literature and recommendations regarding scrub the hub practices was performed to identify nine key components that could be audited by direct observation of staff in clinical areas. The tool was reviewed by stakeholders in infection prevention, infectious diseases and senior nursing roles prior to pilot evaluation. Twenty attempts to access a CVC were audited. In all instances, scrub the hub practices were commenced. However, a 15-second scrub was performed in only 60% of cases, and the hub was permitted to dry in only 65% of instances. With respect to maintaining an aseptic field, the overall compliance was 40%, and compliance was lowest for maintenance of a non-touch technique for key parts and sites, and hand hygiene practices following CVC access. A standardised clinical audit tool for monitoring aseptic access of CVCs enabled identification of practices amendable to targeted intervention and education, such as duration of hub disinfection. This tool would be readily utilised to facilitate quality improvement initiatives in a range of healthcare contexts, including high-risk inpatient and ambulatory care settings.
Publisher: Elsevier BV
Date: 02-2015
DOI: 10.1016/J.JBI.2014.11.009
Abstract: Invasive fungal diseases (IFDs) are associated with considerable health and economic costs. Surveillance of the more diagnostically challenging invasive fungal diseases, specifically of the sino-pulmonary system, is not feasible for many hospitals because case finding is a costly and labour intensive exercise. We developed text classifiers for detecting such IFDs from free-text radiology (CT) reports, using machine-learning techniques. We obtained free-text reports of CT scans performed over a specific hospitalisation period (2003-2011), for 264 IFD and 289 control patients from three tertiary hospitals. We analysed IFD evidence at patient, report, and sentence levels. Three infectious disease experts annotated the reports of 73 IFD-positive patients for language suggestive of IFD at sentence level, and graded the sentences as to whether they suggested or excluded the presence of IFD. Reliable agreement between annotators was obtained and this was used as training data for our classifiers. We tested a variety of Machine Learning (ML), rule based, and hybrid systems, with feature types including bags of words, bags of phrases, and bags of concepts, as well as report-level structured features. Evaluation was carried out over a robust framework with separate Development and Held-Out datasets. The best systems (using Support Vector Machines) achieved very high recall at report- and patient-levels over unseen data: 95% and 100% respectively. Precision at report-level over held-out data was 71% however, most of the associated false-positive reports (53%) belonged to patients who had a previous positive report appropriately flagged by the classifier, reducing negative impact in practice. Our machine learning application holds the potential for developing systematic IFD surveillance systems for hospital populations.
Publisher: Oxford University Press (OUP)
Date: 22-01-2018
DOI: 10.1093/MMY/MYX161
Abstract: We determined the in vitro activity of the novel orotomide antifungal, F901318, against 30 Lomentospora prolificans, 20 Scedosporium apiospermum, 7 S. aurantiacum, and 3 S. boydii, isolates in comparison with standard antifungals. Against L. prolificans, F901318 was the most potent compound (MIC90 0.25 μg/ml) the geometric mean MIC (0.26 μg/ml) was significantly lower (23-80-fold) than those of itraconazole, voriconazole, posaconazole, and isavuconazole (all P < .001), and hotericin B (P < .05). F901318 also had good activity against S. apiospermum, S. aurantiacum, and S. boydii, comparable to that of voriconazole and posaconazole but was more active than isavuconazole for all three species.
Publisher: Oxford University Press (OUP)
Date: 14-10-2021
DOI: 10.1093/JAC/DKAA409
Abstract: Guidance on assessment of the quantity and appropriateness of antifungal prescribing is required to assist hospitals to interpret data effectively and structure quality improvement programmes. To achieve expert consensus on a core set of antifungal stewardship (AFS) metrics and to determine their feasibility for implementation. A literature review was undertaken to develop a list of candidate metrics. International experts were invited to participate in sequential web-based surveys to evaluate the importance and feasibility of metrics in the area of AFS using Delphi methodology. Three surveys were completed. Consensus was predefined as ≥80% agreement on the importance of each metric. Eighty-two experts consented to participate from 17 different countries. Response rate for each survey was & %. The panel included adult and paediatric physicians, microbiologists and pharmacists with erse content expertise. Consensus was achieved for 38 metrics considered important to routinely include in AFS programmes, and related to antifungal consumption (n = 5), quality of antifungal prescribing and management of invasive fungal infection (IFI) (n = 24), and clinical outcomes (n = 9). Twenty-one consensus metrics were considered to have moderate to high feasibility for routine collection. The identified core AFS metrics will provide a framework to comprehensively assess the quantity and quality of antifungal prescribing within hospitals to develop quality improvement programmes aimed at improving IFI prevention, management and patient-centred outcomes. A standardized approach will support collaboration and benchmarking to monitor the efficacy of current prophylaxis and treatment guidelines, and will provide important feedback to guideline developers.
Publisher: Oxford University Press (OUP)
Date: 19-11-2014
DOI: 10.1093/CID/CIU911
Abstract: Strict definition of invasive aspergillosis (IA) cases is required to allow precise conclusions about the efficacy of antifungal therapy. The Global Comparative Aspergillus Study (GCAS) compared voriconazole to hotericin B (AmB) deoxycholate for the primary therapy of IA. Because predefined definitions used for this trial were substantially different from the consensus definitions proposed by the European Organization for Research and Treatment of Cancer/Mycoses Study Group in 2008, we recategorized the 379 episodes of the GCAS according to the later definitions. The objectives were to assess the impact of the current definitions on the classification of the episodes and to provide comparative efficacy for probable roven and possible IA in patients treated with either voriconazole or AmB. In addition to original data, we integrated the results of baseline galactomannan serum levels obtained from 249 (65.7%) frozen s les. The original response assessment was accepted unchanged. Recategorization allowed 59 proven, 178 probable, and 106 possible IA cases to be identified. A higher favorable 12-week response rate was obtained with voriconazole (54.7%) than with AmB (29.9%) (P < .0001). Survival was higher for voriconazole for mycologically documented (probable roven) IA (70.2%) than with AmB (54.9%) (P = .010). Higher response rates were obtained in possible IA treated with voriconazole vs AmB with the same magnitude of difference (26.2% 95% confidence interval [CI], 7.2%-45.3%) as in mycologically documented episodes (24.3% 95% CI, 11.9%-36.7%), suggesting that possible cases are true IA. Recategorization resulted in a better identification of the episodes and confirmed the higher efficacy of voriconazole over AmB deoxycholate in mycologically documented IA.
Publisher: Oxford University Press (OUP)
Date: 13-02-2017
DOI: 10.1093/JAC/DKX047
Publisher: Oxford University Press (OUP)
Date: 30-05-2011
DOI: 10.1093/JAC/DKR186
Abstract: Anidulafungin was found to be non-inferior to and possibly more efficacious than fluconazole for treatment of invasive candidiasis (IC) in a major randomized clinical trial (RCT). There are no data comparing the cost-effectiveness between azoles and echinocandins in treating IC. This economic analysis investigated the cost-effectiveness of anidulafungin compared with fluconazole for treatment of IC in an Australian setting. A decision analytic model was constructed to capture downstream consequences of using either agent for treatment of IC. The main outcomes analysed in the model were treatment success and treatment failure (observed and indeterminate). Outcome probabilities and treatment pathways were derived from a published RCT. Resources used were estimated by an expert panel and cost inputs were derived from the latest Australian resources. The analysis was based on an Australian hospital perspective. Sensitivity analyses were conducted using Monte Carlo simulation. Anidulafungin (AU$74,587) had a higher total cost than fluconazole (AU$60,945) per successfully treated patient, primarily due to its higher acquisition cost. Hospitalization was the main cost driver for both comparators. However, when the rates of mortality in both treatment arms were considered, treatment with anidulafungin was expected to save an additional 0.53 life-years, with an incremental cost-effectiveness ratio (ICER) of AU$25 740 per life-years saved, which was below the implicit ICER threshold value for Australia. The results were robust over a wide range of variables. This is the first economic evaluation of anidulafungin versus fluconazole in the treatment of IC in Australia. Anidulafungin appears to be a cost-effective option.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2012
Publisher: Springer Science and Business Media LLC
Date: 10-10-2017
DOI: 10.1007/S00520-017-3921-3
Abstract: Neutropenic fever (NF) is a common complication of cancer chemotherapy. Patients at low risk of medical complications from NF can be identified using a validated risk assessment and managed in an outpatient setting. This is a new model of care for Australia. This study described the implementation of a sustainable ambulatory program for NF at a tertiary cancer centre over a 12-month period. Peter MacCallum Cancer Centre introduced an ambulatory care program in 2014, which identified low-risk NF patients, promoted early de-escalation to oral antibiotics, and early discharge to a nurse-led ambulatory program. Patients prospectively enrolled in the ambulatory program were compared with a historical-matched cohort of patients from 2011 for analysis. Patient demographics, clinical variables (cancer type, recent chemotherapy, treatment intent, site of presentation) and outcomes were collected and compared. Total cost of inpatient admissions was determined from diagnosis-related group (DRG) codes and applied to both the prospective and historical cohorts to allow comparisons. Twenty-five patients were managed in the first year of this program with a reduction in hospital median length of stay from 4.0 to 1.1 days and admission cost from Australian dollars ($AUD) 8580 to $AUD2360 compared to the historical cohort. Offsetting salary costs, the ambulatory program had a net cost benefit of $AUD 71895. Readmission for fever was infrequent (8.0%), and no deaths were reported. Of relevance to hospitals providing cancer care, feasibility, safety, and cost benefits of an ambulatory program for low-risk NF patients have been demonstrated.
Publisher: Wiley
Date: 11-03-2013
DOI: 10.1111/JOCN.12174
Abstract: To examine Chinese cancer patients' fatigue self-management, including the types of self-management behaviours used, their confidence in using these behaviours, the degree of relief obtained and the factors associated with patients' use of fatigue self-management behaviours. Fatigue places significant burden on patients with cancer undergoing chemotherapy. While some studies have explored fatigue self-management in Western settings, very few studies have explored self-management behaviours in China. Cross-sectional self- and/or interviewer-administered survey. A total of 271 participants with self-reported fatigue in the past week were recruited from a specialist cancer hospital in south-east China. Participants completed measures assessing the use of fatigue self-management behaviours, corresponding self-efficacy, perceived relief levels plus items assessing demographic characteristics, fatigue experiences, distress and social support. A mean of 4.94 (± 2.07 range 1-10) fatigue self-management behaviours was reported. Most behaviours were rated as providing moderate relief and were implemented with moderate self-efficacy. Regression analyses identified that having more support from one's neighbourhood and better functional status predicted the use of a greater number of self-management behaviours. Separate regression analyses identified that greater neighbourhood support predicted greater relief from 'activity enhancement behaviours' and that better functional status predicted greater relief from 'rest and sleep behaviours'. Higher self-efficacy scores predicted greater relief from corresponding behaviours. A range of fatigue self-management behaviours were initiated by Chinese patients with cancer. In idual, condition and environmental factors were found to influence engagement in and relief from fatigue self-management behaviours. Findings highlight the need for nurses to explore patients' use of fatigue self-management behaviours and the effectiveness of these behaviours in reducing fatigue. Interventions that improve patients' self-efficacy and neighbourhood supports have the potential to improve outcomes from fatigue self-management behaviours.
Publisher: Wiley
Date: 2011
DOI: 10.1111/J.1445-5994.2010.02343.X
Abstract: Although the incidence of neutropenic fever (FN) is estimated to be up to 80% for some malignancies, the epidemiological characteristics and economic burden are not well understood for Australian patients. To describe underlying malignant conditions, potential aetiologies, clinical outcomes and healthcare utilization for an Australian population with FN, and to estimate the economic burden of this condition within the Australian healthcare sector. Epidemiological features of FN were extracted from a population-based hospital morbidity dataset, the Victorian Admitted Episodes Dataset (VAED), for a 12-month period (2008). These were analysed according for a range of malignancy categories. Economic burden of hospitalizations was estimated according to data presented in the Round 12 National Hospital Cost Data Collection Report. A total of 2599 admitted episodes across 92 Victorian hospitals fulfilled inclusion criteria for FN. Metropolitan hospitalizations accounted for 79% episodes. FN illness comprised underlying solid tumours diagnoses (40%), followed by leukaemia (29.3%), lymphoma (22%) and myeloma (8.5%). Length of hospital stay was >15 days for approximately one-third of hospitalizations. intensive care unit admission rates were 5.9-11.7%. Weighted average costs of hospitalization (AUD) for solid tumours, lymphoma, myeloma and leukaemia were $8309 ± $391, 18,145 ± $1602, $21,764 ± $1289 and $22,596 ± $2618 respectively. Using VAED indices, epidemiological features of Australian patients with FN appear comparable with international reports. In contrast to US data, estimated healthcare costs are up to 50% lower in the Australian healthcare sector. These data offer important insights for prioritizing of research agendas and resource allocation.
Publisher: Wiley
Date: 20-12-2013
DOI: 10.1111/TID.12043
Abstract: Toxoplasmosis is increasingly diagnosed after hematopoietic stem cell transplantation (HSCT) and is associated with considerable morbidity and mortality. In the majority of cases, reactivation of latent disease secondary to impaired cellular and humoral immunity after HSCT is believed to be the main pathogenetic mechanism. Hence, primary toxoplasmosis is rarely considered in the differential diagnosis of infections after HSCT in a recipient who is seronegative for Toxoplasma gondii pre-transplant. We herein report a seronegative patient with acute T-cell lymphoblastic leukemia, who developed primary disseminated toxoplasmosis 5 months after HSCT from a seronegative unrelated donor. A review of all reported cases of primary toxoplasmosis after HSCT revealed significantly increased morbidity and mortality. Patients with negative pre-transplant Toxoplasma serology should therefore be considered at risk for toxoplasmosis after allogeneic HSCT. Possible prevention and monitoring strategies for seronegative recipients are reviewed and discussed in detail.
Publisher: Springer Science and Business Media LLC
Date: 18-09-2017
DOI: 10.1038/BMT.2017.195
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 22-09-2020
Publisher: Wiley
Date: 07-2007
DOI: 10.1111/J.1399-3062.2007.00203.X
Abstract: Breakthrough invasive fungal infections among patients with hematologic malignancies receiving voriconazole are being reported with increasing frequency, with zygomycete infections predominating. We report a case of disseminated Scedosporium prolificans infection in a patient receiving voriconazole prophylaxis. Despite poor in vitro activity of voriconazole for this organism, synergy studies using the checkerboard method demonstrated synergy with the combination of voriconazole and terbinafine. This regimen, in conjunction with central venous line removal and intravitreal voriconazole, contributed to the recovery of the patient. S. prolificans is a life-threatening mold that should be considered in patients with breakthrough invasive fungal infections while on voriconazole prophylaxis.
Publisher: Wiley
Date: 04-2009
Publisher: Elsevier BV
Date: 09-2016
DOI: 10.1016/J.CMI.2016.01.005
Abstract: Mucormycosis is the second most common cause of invasive mould infection and causes disease in erse hosts, including those who are immuno-competent. We conducted a multicentre retrospective study of proven and probable cases of mucormycosis diagnosed between 2004-2012 to determine the epidemiology and outcome determinants in Australia. Seventy-four cases were identified (63 proven, 11 probable). The majority (54.1%) were caused by Rhizopus spp. Patients who sustained trauma were more likely to have non-Rhizopus infections relative to patients without trauma (OR 9.0, p 0.001, 95% CI 2.1-42.8). Haematological malignancy (48.6%), chemotherapy (42.9%), corticosteroids (52.7%), diabetes mellitus (27%) and trauma (22.9%) were the most common co-morbidities or risk factors. Rheumatological/autoimmune disorders occurred in nine (12.1%) instances. Eight (10.8%) cases had no underlying co-morbidity and were more likely to have associated trauma (7/8 87.5% versus 10/66 15.2% p <0.001). Disseminated infection was common (39.2%). Apophysomyces spp. and Saksenaea spp. caused infection in immuno-competent hosts, most frequently associated with trauma and affected sites other than lung and sinuses. The 180-day mortality was 56.7%. The strongest predictors of mortality were rheumatological/autoimmune disorder (OR = 24.0, p 0.038 95% CI 1.2-481.4), haematological malignancy (OR = 7.7, p 0.001, 95% CI 2.3-25.2) and admission to intensive care unit (OR = 4.2, p 0.02, 95% CI 1.3-13.8). Most deaths occurred within one month. Thereafter we observed ergence in survival between the haematological and non-haematological populations (p 0.006). The mortality of mucormycosis remains particularly high in the immuno-compromised host. Underlying rheumatological/autoimmune disorders are a previously under-appreciated risk for infection and poor outcome.
Publisher: Elsevier BV
Date: 2013
DOI: 10.1016/J.JCHROMB.2012.11.030
Abstract: The quantification of voriconazole concentration in lung epithelial lining fluid to facilitate the management of pulmonary fungal colonisation or aspergillosis is of increasing interest. An accurate and reproducible high-performance liquid chromatography method to quantify voriconazole in human bronchoalveolar lavage (BAL) fluid was developed and validated. BAL s les were concentrated by freeze-drying and reconstituted with water prior to deproteinisation. Separation was achieved with a C18 column employing fluorescence detection (excitation: 260nm, emission: 370nm). The calibration curves were linear from 2.5 to 500ng/mL. The intra- and inter-day precisions were within 7%. Accuracies ranged from 102% to 107%. The clinical applicability was established by successful measurement of voriconazole concentrations in lung transplant recipients. The assay provides an alternative approach for those with negligible access to liquid chromatography-tandem mass spectrometry instrumentation.
Publisher: Cold Spring Harbor Laboratory
Date: 10-09-2019
DOI: 10.1101/764787
Abstract: Multidrug-resistant organisms (MDROs) disproportionately affect hospitalized patients due to the combination of comorbidities, frequent antimicrobial use, and in-hospital MDRO transmission. Identification of MDRO transmission by hospital microbiology laboratories is difficult due to limitations of existing typing methods. We conducted a prospective multicenter genomics implementation study (8 hospitals, 2800 beds) from 24 th April to 18 th June 2017 in Melbourne, Australia. Clinical and screening isolates from hospital inpatients were collected for six MDROs ( vanA VRE, MRSA, ESBL E. coli [ESBL-Ec] and Klebsiella pneumoniae [ESBL-Kp], and carbapenem-resistant Pseudomonas aeruginosa [CRPa] and Acinetobacter baumannii [CRAb]), sequenced (Illumina NextSeq) and analyzed using open-source tools. MDRO transmission was assessed by genomics (core SNP phylogeny, grouped by species and ST) and compared to epidemiologic data. 408 isolates were collected from 358 patients 47.5% were screening isolates. ESBL-Ec was most common (52.5%), then MRSA (21.6%), vanA VRE (15.7%) and ESBL-Kp (7.6%). We define the transmission rate for each MDRO by genomics and epidemiology 31.6% of all study patients had potential genomic links to other study isolates 86% of these were confirmed by epidemiologic links (probable or possible transmission). The highest transmission rates occurred with van A VRE (88.4% of patients). Combining genomics with high-quality epidemiologic data gives substantial insights into the burden and distribution of critical MDROs in hospitals, including in-hospital transmission. By defining transmission rates by genomics, we hope to enable comparisons over time and between sites, and introduce this as a new outcome measure to assess the efficacy of infection control interventions.
Publisher: Wiley
Date: 12-2014
DOI: 10.1111/IMJ.12601
Abstract: Healthcare-associated fungal outbreaks impose a substantial economic burden on the health system and typically result in high patient morbidity and mortality, particularly in the immunocompromised host. As the population at risk of invasive fungal infection continues to grow due to the increased burden of cancer and related factors, the need for hospitals to employ preventative measures has become increasingly important. These guidelines outline the standard quality processes hospitals need to accommodate into everyday practice and at times of healthcare-associated outbreak, including the role of antifungal stewardship programmes and best practice environmental s ling. Specific recommendations are also provided to help guide the planning and implementation of quality processes and enhanced surveillance before, during and after high-risk activities, such as hospital building works. Areas in which information is still lacking and further research is required are also highlighted.
Publisher: Frontiers Media SA
Date: 09-11-2017
Publisher: AMPCo
Date: 24-05-2020
DOI: 10.5694/MJA2.50612
Publisher: Informa UK Limited
Date: 2001
DOI: 10.3109/10428190109057998
Abstract: We describe a unique case of a patient with a three-year history of idiopathic CD4(+) T cell lymphopenia (HIV negative) who presented with stage IV diffuse large cell non Hodgkin's lymphoma with t(8 ). Despite the severe lymphopenia, the patient tolerated intensive chemotherapy well and at 18 months, remains in complete remission.
Publisher: Elsevier BV
Date: 12-2013
DOI: 10.1016/J.COLEGN.2012.09.004
Abstract: Women who experience cancer treatment-induced menopause are at risk of long-term chronic morbidity. This risk can be prevented or offset with adherence to health promotion and risk reduction guidelines. The purpose of this study was to explore health behaviours in younger female survivors of cancer and the variables (quality of life and psychological distress) believed to moderate health behaviours. Cross-sectional survey of a convenience s le of women (n=85) in southeast Queensland. Health behaviour and health status were elicited with items from the Australian Health Survey and the Behavioural Risk Factor Surveillance System. The WHO Quality of Life (Brief) measured participants' self-reported quality of life and their satisfaction with their health. The Brief Symptom Inventory-18 measured psychological distress. Higher self-reported health status was associated with regular exercise and better quality of life. However, a substantial proportion of participants did not engage in the physical activity, dietary or cervical screening practices recommended by Australian guidelines. The participants require education regarding the benefits of diet, exercise, weight loss and decreased alcohol intake, as well as information on future health risks and possible comorbidities. These education sessions could be addressed by a nurse-led health promotion model of care at the time of discharge or in the community.
Publisher: Ferrata Storti Foundation (Haematologica)
Date: 28-06-2017
Publisher: Informa UK Limited
Date: 2001
DOI: 10.3109/10428190109097734
Abstract: We describe a case of successful treatment of rhinocerebral mucormycosis in a patient with multiple myeloma. Therapeutic strategies used included liposomal hotericin, hyperbaric oxygen, GM-CSF and liposomal nystatin.
Publisher: Hindawi Limited
Date: 09-2004
Publisher: Elsevier BV
Date: 05-2009
DOI: 10.1016/J.BLRE.2008.10.003
Abstract: Bloodstream infections are an important cause of morbidity and mortality in the haematology population, and may contribute to delayed administration of chemotherapy, increased length of hospitalisation, and increased healthcare expenditure. For gram-positive, gram-negative, anaerobic and fungal infections, specific risk factors are recognised. Unique host and environmental factors contributing to pathogenesis are acknowledged in this population. Trends in spectrum and antimicrobial susceptibility of pathogens are examined, and potential contributing factors are discussed. These include the widespread use of empiric antimicrobial therapy, increasingly intensive chemotherapeutic regimens, frequent use of central venous catheters, and local infection control practices. In addition, the risks and benefits of prophylaxis, and spectrum of endemic flora are identified as relevant factors within in idual centres. Finally, challenges are presented regarding prevention, early detection, surveillance and prophylaxis. To reduce the rate and impact of bloodstream infections multifaceted and customised strategies are required within in idual haematology units.
Publisher: Oxford University Press (OUP)
Date: 18-04-2017
Abstract: A simple test to identify recovery of CMV-specific T-cell immunity following hematopoietic stem cell transplantation (HSCT) could assist clinicians in managing CMV-related complications. In an observational, multicenter, prospective study of 94 HSCT recipients we evaluated CMV-specific T-cell immunity at baseline, 3, 6, 9, and 12 months after transplant using the Quantiferon-CMV, an enzyme-linked immunosorbent spot assay (ELISpot), and intracellular cytokine staining. At 3 months after HSCT, participants who developed CMV disease (n = 8) compared with CMV reactivation (n = 26) or spontaneous viral control (n = 25) had significantly lower CD8+ T-cell production of interferon-γ (IFN-γ) in response to CMV antigens measured by Quantiferon-CMV (P = .0008). An indeterminate Quantiferon-CMV result had a positive predictive value of 83% and a negative predictive value of 98% for identifying participants at risk of further CMV reactivation. Participants experiencing CMV reactivation compared with patients without CMV reactivation had a reduced proportion of polyfunctional (IFN-γ+/tumor necrosis factor α-positive) CD4+ and CD8+ T cells and a higher proportion of interleukin 2-secreting cells (P = .01 and P = .002, respectively). Quantifying CMV-specific T-cell immunity after HSCT can identify participants at increased risk of clinically relevant CMV-related outcomes.
Publisher: Elsevier BV
Date: 08-2016
DOI: 10.1016/J.CMI.2016.01.011
Abstract: There are three broad groups of non-Aspergillus moulds: the mucormycetes, the hyalohyphomycetes and the phaeohyphomycetes. Infections with these pathogens are increasingly reported, particularly in the context of increasing use of immunosuppressant agents and improved diagnostics. The epidemiology of non-Aspergillus mould infections varies with geography, climate and level of immunosuppression. Skin and soft-tissue infections are the predominant presentation in the immunocompetent host and pulmonary and other invasive infections in the immunocompromised host. The more common non-Aspergillus moulds include Rhizopus, Mucor, Fusarium and Scedosporium species however, other emerging pathogens are Rasamsonia and Verruconis species, which are discussed in this article. Outbreaks of non-Aspergillus mould infections have been increasingly reported, with contaminated medical supplies and natural disasters as common sources. Currently culture and other conventional diagnostic methods are the cornerstone of diagnosis. Molecular methods to directly detect and identify mould pathogens in tissue and body fluids are increasingly used.
Publisher: CSIRO Publishing
Date: 2015
DOI: 10.1071/MA15020
Publisher: Elsevier BV
Date: 05-2015
DOI: 10.1016/J.CMI.2014.12.021
Abstract: The epidemiology of invasive fungal disease (IFD) due to filamentous fungi other than Aspergillus may be changing. We analysed clinical, microbiological and outcome data in Australian patients to determine the predisposing factors and identify determinants of mortality. Proven and probable non-Aspergillus mould infections (defined according to modified European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria) from 2004 to 2012 were evaluated in a multicentre study. Variables associated with infection and mortality were determined. Of 162 episodes of non-Aspergillus IFD, 145 (89.5%) were proven infections and 17 (10.5%) were probable infections. The pathogens included 29 fungal species/species complexes mucormycetes (45.7%) and Scedosporium species (33.3%) were most common. The commonest comorbidities were haematological malignancies (HMs) (46.3%) diabetes mellitus (23.5%), and chronic pulmonary disease (16%) antecedent trauma was present in 21% of cases. Twenty-five (15.4%) patients had no immunocompromised status or comorbidity, and were more likely to have acquired infection following major trauma (p <0.01) 61 (37.7%) of cases affected patients without HMs or transplantation. Antifungal therapy was administered to 93.2% of patients (median 68 days, interquartile range 19-275), and adjunctive surgery was performed in 58.6%. The all-cause 90-day mortality was 44.4% HMs and intensive-care admission were the strongest predictors of death (both p <0.001). Survival varied by fungal group, with the risk of death being significantly lower in patients with dematiaceous mould infections than in patients with other non-Aspergillus mould infections. Non-Aspergillus IFD affected erse patient groups, including non-immunocompromised hosts and those outside traditional risk groups therefore, definitions of IFD in these patients are required. Given the high mortality, increased recognition of infections and accurate identification of the causative agent are required.
Publisher: Elsevier BV
Date: 05-2017
DOI: 10.1016/J.VACCINE.2017.03.063
Abstract: To compare the antibody response to influenza between health care workers (HCWs) who have received multiple vaccinations (high vaccination group) and those who have received fewer vaccinations (low vaccination group). Prospective serosurvey. Tertiary referral hospital. Healthcare workers. Healthcare workers were vaccinated with the 2015 southern hemisphere trivalent influenza vaccine. Influenza antibody titres were measured pre-vaccination, 21-28days post-vaccination and 6months post-vaccination. Antibody titres were measured using the haemagglutination inhibition assay. Levels of seropositivity and estimated geometric mean titres were calculated. Of the 202 HCWs enrolled, 182 completed the study (143 high vaccination and 39 low vaccination). Both vaccination groups demonstrated increases in post-vaccination geometric mean titres, with greater gains in the low vaccination group. Seropositivity remained high in both high and low vaccination groups post-vaccination. The highest fold rise was observed among HCWs in the low vaccination group against the H3N2 component of the vaccine. Both high and low vaccination groups in our study demonstrated protective antibody titres post-vaccination. The findings from the current study are suggestive of decreased serological response among highly vaccinated HCWs. More studies with larger s le sizes and a greater number of people in the vaccine-naïve and once-vaccinated groups are required to confirm or refute these findings before making any policy changes.
Publisher: Oxford University Press (OUP)
Date: 2006
DOI: 10.1080/13693780600826699
Abstract: Invasive Aspergillosis (IA) is now the leading infectious cause of mortality in patients with haematological malignancies. Studies have identified those patient groups and the time-periods associated with high-risk for IA. The current management strategies for IA include prophylaxis and empiric antifungal therapy (EAFT). The rationale for prophylaxis in high-risk patients exists. However toxicities, drug interactions and breakthrough infections limit the benefits and the optimal duration for prophylaxis remains unknown. In recent EAFT studies in high-risk patients, <10% of persistent febrile neutropenic episodes were due to IA, suggesting that a disproportionate number of patients are treated with EAFT resulting in unnecessary drug-related costs. An increasing proportion of IA occurs in the absence of fevers and neutropenia, thus use of febrile neutropenia as the trigger to administer antifungal therapy will fail a significant proportion of patients. Recent research efforts have focused on the development of sensitive, specific and rapid diagnostic tests for IA, such as Aspergillus polymerase chain reaction (PCR) and antigen testing, which may be of value in guiding pre-emptive treatment strategies. However, studies evaluating the impact of pre-emptive therapy on patient outcomes and health-care costs have yet to be completed. Practical issues such as the combination of tests used and frequency of testing need to be resolved.
Publisher: Wiley
Date: 23-08-2023
DOI: 10.1111/TID.14138
Publisher: Wiley
Date: 25-03-2013
DOI: 10.1111/TID.12071
Abstract: Invasive fungal infection (IFI) is associated with high mortality in lung transplant (LTx) recipients. Data for voriconazole use in preemptive treatment remain scant. A single-center, retrospective cohort study was conducted to investigate the efficacy and safety of voriconazole preemptive treatment for post-LTx colonization. We reviewed 62 adult LTx patients, who received their first course of voriconazole prophylaxis (i.e., as preemptive treatment) between July 2003 and June 2010. Outcomes were determined at 6 and 12 months after commencing therapy. Aspergillus fumigatus (75.8%) was the most common colonizing isolate. Median duration of voriconazole prophylaxis was 85 days. At 6 months, 1 LTx patient (1.6%) had IFI, 47 (75.8%) cleared their colonizing isolate, 3 (4.8%) had persistent colonization, 7 (11.3%) had recurrent colonization, 1 (1.6%) had new colonization, 2 (3.2%) had aspergilloma, and 1 (1.6%) was clinically unstable with no culture results. Sixteen (25.8%) had died by 12 months. Ten (16.1%) had likely drug-related hepatotoxicity. LTx patients with diabetes mellitus within 30 days before commencing prophylaxis were at higher risk of recurrent Aspergillus colonization at 6 months (P = 0.030). Chronic rejection within 30 days before prophylaxis was associated with 12-month mortality (P = 0.007). Voriconazole preemptive treatment resulted in low incidence of IFI and IFI-related mortality.
Publisher: Oxford University Press (OUP)
Date: 08-2018
DOI: 10.1093/JAC/DKY286
Abstract: The European Conference on Infections in Leukaemia (ECIL) updated its guidelines on antifungal prophylaxis for adults using the grading system of IDSA. The guidelines were extended to provide recommendations for other haematological diseases besides AML and recipients of an allogeneic haematopoietic stem cell transplantation (HSCT). Posaconazole remains the drug of choice when the incidence of invasive mould diseases exceeds 8%. For patients undergoing remission-induction chemotherapy for AML and myelodysplastic syndrome (MDS), fluconazole can still offer an alternative provided it forms part of an integrated care strategy that includes screening with biomarkers and imaging. Similarly, aerosolized liposomal hotericin B combined with fluconazole can be considered for patients at high risk of invasive mould diseases but other formulations of the polyene are discouraged. Fluconazole is still recommended as primary prophylaxis for patients at low risk of invasive mould diseases during the pre-engraftment phase of allogeneic HSCT whereas only a moderate recommendation could be made for itraconazole, posaconazole and voriconazole for patients at high risk. Posaconazole is strongly recommended for preventing invasive mould disease post-engraftment but only when graft-versus-host disease (GvHD) was accompanied by other risk factors such as its severity, use of an alternative donor or when unresponsive to standard corticosteroid therapy. The need for primary prophylaxis for other patient groups was less clear and should be defined by the estimated risk of invasive fungal disease (IFD).
Publisher: Informa UK Limited
Date: 17-05-2019
DOI: 10.1080/10428194.2019.1590570
Abstract: Invasive fungal disease (IFD) is responsible for significant morbidity and mortality in patients with acute leukemia. Antifungal stewardship (AFS) programs are utilized in this patient group but have been infrequently evaluated in clinical practice. Adults diagnosed with acute leukemia at an Australian tertiary center over two years were identified, with subsequent auditing of IFD prophylaxis and treatment, and identification of further opportunities for AFS activities. Proven or probable IFD occurred in 6% of cases, including 14% of acute lymphoblastic leukemia (ALL) patients and 6% of acute myeloid leukemia (AML) patients. Mold-active antifungal prophylaxis was used in 84% of cases overall, including in 94% of AML cases and 23% of ALL cases. Local auditing identified target areas for AFS in this complex patient cohort, including modification of clinical guidelines, enhanced patient screening, improved access to fungal diagnostics and therapeutic drug monitoring, and the establishment of a specialized, embedded AFS program.
Publisher: Elsevier BV
Date: 07-2018
Publisher: American Society for Microbiology
Date: 05-2011
DOI: 10.1128/AAC.01423-10
Abstract: Studies using patient-level data to determine the attributable cost of invasive fungal diseases (IFDs) are few. Using a case-control study with activity-based costing of patients admitted to a quaternary hospital from 2002 to 2007, we determined attributable hospitalization cost (and 12 weeks thereafter), length of stay (LOS), and costly antifungal treatment (C-AT liposomal hotericin B, voriconazole, posaconazole, caspofungin), expressed as defined daily doses (DDDs) per IFD episode, in patients with hematological malignancies and hematopoietic stem cell recipients. Matching criteria and median regression modeling controlled for confounding variables, including LOS prior to IFD onset. Multiple mycoses were identified in 43 matched case-control pairs ( n = 86). A separate sensitivity analysis included 22 unmatched patients. IFD status was associated with a median excess cost of AU$30,957 (95% confidence interval [CI] = AU$2,368 to AU$59,546 P = 0.034), approximating at purchasing power parity US$21,203 (95% CI = US$1,622 to US$40,784) and €15,788 (95% CI = €1,208 to €30,368), increasing to AU$80,291 (95% CI = AU$33,636 to AU$126,946 P = 0.001), i.e., US$54,993 (95% CI = US$23,038 to US$86,948) and €40,948 (95% CI = €17,154 to €64,742), with intensive care unit (ICU) requirement. Cost determinants were pharmacy costs (64% P 0.001) inclusive of antifungal treatment (27% P 0.001) and ward costs (27% P = 0.091), with proportions persisting through 12 weeks for 25 surviving matched pairs (pharmacy, 60% [ P = 0.12] ward, 31% [ P = 0.21]). Median LOS was not significantly increased unless unmatched patients were included (8 days, 95% CI = 1.8 to 14 days P = 0.012). Excess C-ATs were 17 DDDs (95% CI = 15 to 19 DDDs P 0.001) per case patient and 19 DDDs (95% CI = 16 to 22 DDDs P 0.001) per ICU patient. The sensitivity analysis was confirmatory (for median cost, AU$29,441, 95% CI = AU$5,571 to AU$53,310, P = 0.016 for C-AT, 17 DDDs, 95% CI = 16 to 18 DDDs, P 0.001). IFD results in increased hospital and ICU costs, with pharmacy costs, including antifungal treatment, being major determinants. Consumption of costly antifungal drugs may be a novel resource metric with wider generalizability than cost alone.
Publisher: AMPCo
Date: 13-05-2020
DOI: 10.5694/MJA2.50607
Publisher: Springer Science and Business Media LLC
Date: 23-03-2012
Publisher: Elsevier BV
Date: 05-2021
Publisher: Elsevier BV
Date: 06-2021
Publisher: Oxford University Press (OUP)
Date: 11-09-2021
DOI: 10.1093/JAC/DKAB317
Abstract: Invasive aspergillosis (IA) is an acute infection affecting patients who are immunocompromised, as a result of receiving chemotherapy for malignancy, or immunosuppressant agents for transplantation or autoimmune disease. Whilst criteria exist to define the probability of infection for clinical trials, there is little evidence in the literature or clinical guidelines on when to change antifungal treatment in patients who are receiving prophylaxis or treatment for IA. To try and address this significant gap, an advisory board of experts was convened to develop criteria for the management of IA for use in designing clinical trials, which could also be used in clinical practice. For primary treatment failure, a change in antifungal therapy should be made: (i) when mycological susceptibility testing identifies an organism from a confirmed site of infection, which is resistant to the antifungal given for primary therapy, or a resistance mutation is identified by molecular testing (ii) at, or after, 8 days of primary antifungal treatment if there is increasing serum galactomannan, or galactomannan positivity in serum, or bronchoalveolar lavage fluid when the antigen was previously undetectable, or there is sudden clinical deterioration, or a new clearly distinct site of infection is detected and (iii) at, or after, 15 days of primary antifungal treatment if the patient is clinically stable but with ≥2 serum galactomannan measurements persistently elevated compared with baseline or increasing, or if the original lesions on CT or other imaging, show progression by & % in size in the context of no apparent change in immune status.
Publisher: Wiley
Date: 2011
DOI: 10.1111/J.1445-5994.2010.02340.X
Abstract: Administration of empiric antimicrobial therapy is standard practice in the management of neutropenic fever, but there remains considerable debate about the selection of an optimal regimen. In view of emerging evidence regarding efficacy and toxicity differences between empiric treatment regimens, and strong evidence of heterogeneity in clinical practice, the current guidelines were developed to provide Australian clinicians with comprehensive guidance for selecting an appropriate empiric strategy in the setting of neutropenic fever. Beta-lactam monotherapy is presented as the treatment of choice for all clinically stable patients while early treatment with combination antibiotic therapy is considered for patients at higher risk. Due consideration is given to the appropriate use of glycopeptides in this setting. Several clinical caveats, accounting for institution- and patient-specific risk factors, are provided to help guide the judicious use of the agents described. Detailed recommendations are also provided regarding time to first dose, timing of blood cultures, selection of a first-line antibiotic regimen, subsequent modification of antibiotic choice and cessation of therapy.
Publisher: Wiley
Date: 03-02-2021
DOI: 10.1111/JPC.15330
Abstract: The Australian ‘There is no place like home’ project is implementing a paediatric low‐risk febrile neutropenia (FN) programme across eight paediatric hospitals. We sought to identify the impact of the coronavirus disease 2019 (COVID‐19) pandemic on programme implementation. Paediatric oncology, infectious diseases and emergency medicine health‐care workers and parent/carers were surveyed to explore the impact of the COVID‐19 pandemic on home‐based FN care. Online surveys were distributed nationally to health‐care workers involved in care of children with FN and to parents or carers of children with cancer. Surveys were completed by 78 health‐care workers and 32 parents/carers. Overall, 95% of health‐care workers had confidence in the safety of home‐based FN care, with 35% reporting changes at their own hospitals in response to the pandemic that made them more comfortable with this model. Compared to pre‐pandemic, % of parent/carers were now more worried about attending the hospital with their child and % were interested in receiving home‐based FN care. Among both groups, increased telehealth access and acceptance of home‐based care, improved patient quality of life and reduced risk of nosocomial infection were identified as programme enablers, while re‐direction of resources due to COVID‐19 and challenges in implementing change during a crisis were potential barriers. There is strong clinician and parent/carer support for home‐based management of low‐risk FN across Australia. Changes made to the delivery of cancer care in response to the pandemic have generally increased acceptance for home‐based treatments and opportunities exist to leverage these to refine the low‐risk FN programme.
Publisher: Informa UK Limited
Date: 04-2013
DOI: 10.1586/ERP.13.3
Abstract: Invasive fungal infections incur considerable costs to healthcare and are associated with high mortality. These infections are increasing, due in part to more intensive immunosuppressive regimens with longer periods of neutropenia for patients treated for conditions such as cancer and hematopoietic stem cell transplantation. Therapeutic strategies in treating invasive fungal infections include the initiation of empiric antifungal therapy. This early treatment is triggered by fever that is unresponsive to 48-72 h of broad-spectrum antibiotic therapy in high-risk patients, prior to diagnosis. Several antifungal agents are available for this purpose. Informed decisions with respect to the choice of antifungal drug require clinicians to consider both efficacy data of a particular drug and the economic consequences of using the drug. This enables a treatment decision to be based not only on drug acquisition cost, but also expenses associated with hospitalization, monitoring and managing adverse effects to the treatment(s) chosen.
Publisher: Oxford University Press (OUP)
Date: 03-05-2023
DOI: 10.1093/OFID/OFAD232
Abstract: Clostridioides difficile infection (CDI) is associated with significant morbidity and mortality in both healthcare and community settings. We aimed to define the predisposing factors, risks for severe disease, and mortality determinants of CDI in eastern Australia over a 1-year period. This is an observational retrospective study of CDI in hospitalized patients aged ≥18 years in 6 tertiary institutions from 1 January 2016 to 31 December 2016. Patients were identified through laboratory databases and medical records of participating institutions. Clinical, imaging, and laboratory data were input into an electronic database hosted at a central site. A total of 578 patients (578 CDI episodes) were included. Median age was 65 (range, 18–99) years and 48.2% were male. Hospital-onset CDI occurred in 64.0%. Recent antimicrobial use (41.9%) and proton pump inhibitor use (35.8%) were common. Significant risk factors for severe CDI were age & years (P & .001), malignancy within the last 5 years (P & .001), and surgery within the previous 30 days (P & .001). Significant risk factors for first recurrence included severe CDI (P = .03) and inflammatory bowel disease (P = .04). Metronidazole was the most common regimen for first episodes of CDI with 65.2% being concordant with Australian treatment guidelines overall. Determinants for death at 60 days included age ≥65 years (P = .01), severe CDI (P & .001), and antibiotic use within the prior 30 days (P = .02). Of those who received metronidazole as first-line therapy, 10.1% died in the 60-day follow-up period, compared to 9.8% of those who received vancomycin (P = .86). Patients who experience CDI are vulnerable and require early diagnosis, clinical surveillance, and effective therapy to prevent complications and improve outcomes.
Publisher: Elsevier BV
Date: 03-2014
DOI: 10.1016/J.IJANTIMICAG.2013.08.010
Abstract: Candidaemia and invasive candidiasis (IC) complicate modern medical therapy, contributing to high morbidity and mortality. Managing candidiasis is costly, with an additional healthcare expenditure of nearly US$300 million annually. Recent consensus guidelines have suggested the use of newer antifungal agents, such as echinocandins, for the treatment of candidaemia and IC owing to promising clinical outcomes compared with older-generation antifungal agents, but at higher drug acquisition and administration costs. Comprehensive cost-effectiveness data for echinocandins in treating candidaemia and IC remain relatively scant, underlining the need for more studies to incorporate robust economic analyses into clinical decisions. Assessment of the cost efficiencies of these expensive antifungal agents is essential for maximising health outcomes within the constraints of healthcare resources. This review will explore the epidemiology of candidaemia and IC in the context of clinical and economic aspects of the antifungal agents used to treat IC, especially the echinocandins. Standardising the outcome measure, methodology and reporting of results used in economic studies is central to ensure validity and comparability of the findings. Future studies comparing the economic advantages of all available antifungal treatment options and in the context of new diagnostic tools for fungal infections are anticipated.
Publisher: Wiley
Date: 06-2003
DOI: 10.1046/J.1440-172X.2003.00421.X
Abstract: This paper explores the issues related to rural people with cancer whose choice of radiotherapy treatment necessitated travel and accommodation in a metropolitan centre. Semi-structured interviews with 46 participants, from the Toowoomba and Darling Downs region of Queensland, Australia, were conducted and the data thematically analysed. The specific themes identified were: being away from loved ones, maintaining responsibilities whilst undergoing treatment, emotional stress, burden on significant others, choice about radiotherapy as a treatment, travel and accommodation, and financial burden. This study supports the need for a radiotherapy centre in the location of Toowoomba as a way of providing some equity and access to such treatment for the rural people of Queensland.
Publisher: Wiley
Date: 20-11-2013
DOI: 10.1111/MYC.12154
Abstract: Infective endocarditis due to Candida sp. has a high mortality rate. Traditionally, management involves early surgery and prolonged hotericin ± flucytosine. We report a case of Candida parapsilosis bileaflet mitral valve endocarditis cured with anidulafungin and fluconazole, and review the role of echinocandins in the management of Candida endocarditis.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2008
Publisher: Informa UK Limited
Date: 07-2012
DOI: 10.1586/ERI.12.56
Abstract: The subtitle of the Australasian Society for Infectious Diseases Annual Scientific Meeting was 'Sailing into the Future', and speakers from both adult and pediatric infectious diseases explored this theme in relation to the management of sepsis. The future will entail better risk prediction tools for patients at risk for sepsis. Such risk prediction tools are likely to incorporate genetic profiling of the host to identify the groups at highest risk for disease and death. Focused diagnostic testing in these patients will include molecular diagnostics for early detection of infection.
Publisher: Wiley
Date: 17-04-2020
DOI: 10.1002/RMV.2108
Publisher: Elsevier BV
Date: 09-2021
Publisher: Wiley
Date: 12-09-2021
DOI: 10.1111/TID.13719
Abstract: The use of antithymocyte globulin (ATG) in allogeneic hematopoietic cell transplant (HCT) is associated with an increased risk of Epstein–Barr virus (EBV) reactivation and post‐transplant lymphoproliferative disorders (PTLD). The dynamics and outcomes of EBV‐DNAemia are not well described in this population. We retrospectively assessed the kinetics of EBV‐DNAemia after ATG conditioning of HCT recipients. Receiver operating characteristic (ROC) curves were used to assess EBV‐DNAemia to predict EBV‐PTLD in this group. A total of 174/405 (43%) consecutive HCT recipients from two centers met inclusion criteria of ATG conditioned, non‐B‐cell lymphoma patients. Of these with EBV‐DNA measured using standardized IU/ml, 78.6% (92/117) developed EBV‐DNAemia: 62% spontaneously resolved 19% cleared after preemptive rituximab, and 13% developed EBV‐PTLD. ROC curve analysis using maximum pre‐EBV‐PTLD EBV‐DNAemia, demonstrated an AUC of 0.912 with EBV‐DNAemia of 9782 IU/ml, associated with 82.6% sensitivity and 94.4% specificity for development of EBV‐PTLD. Median time for EBV‐DNAemia to increase from initial detection to IU/ml was 7 days to 000 IU/ml, 12 days and to 000 IU/ml, 18 days. Median EBV‐DNAemia level prior to administration of rituximab was significantly lower in patients with successful preemptive treatment, compared with those who developed EBV‐PTLD (3.41 log 10 IU/ml [3.30–3.67] vs. 4.34 log 10 IU/ml [3.85–5.13], p = .002 i.e., 2628 IU/ml vs. 21 965 IU/ml, respectively). EBV‐DNAemia 000 IU/ml was the strongest predictor of the development of EBV‐PTLD, and progression to this level was rapid in ATG‐conditioned HCT recipients. This information may guide EBV‐PTLD management strategies in these high‐risk patients.
Publisher: Springer Science and Business Media LLC
Date: 11-2009
DOI: 10.1007/S11908-009-0061-Z
Abstract: Invasive fungal infection (IFI) is an important cause of morbidity and mortality in patients with hematologic malignancy, prolonged neutropenia, or after hematopoietic stem cell transplant. Antifungal prophylaxis prevents IFI in high-risk hematology patients. This article discusses recent developments in antifungal prophylaxis, focusing on those expected to affect patient management. Significant advances have occurred in understanding risk stratification and assessment of in idual patient risk for drug-drug interactions, toxicity, or variations in pharmacokinetics choice of antifungal prophylaxis strategy, drug, dose, route, and regimen therapeutic drug monitoring cost effectiveness of prophylaxis and the significance of breakthrough IFI. Research over the coming decade is likely to fundamentally alter antifungal prophylaxis by allowing clinicians to make in idualized decisions for their patients informed by rapid, detailed, and personalized risk-benefit analyses.
Publisher: Elsevier BV
Date: 02-2008
DOI: 10.1016/J.JHIN.2007.10.017
Abstract: European studies have suggested that the esp gene and other virulence factors have roles in vancomycin-resistant Enterococcus faecium (VREfm) infections. The aim of this study was to examine the relationship between the spectrum of clinical disease and putative virulence factors in vanB VREfm isolates. A multiplex polymerase chain reaction was used to lify potential virulence genes (asa1, gel E, cylA, esp and hyl) in VREfm isolates obtained from an Australian population of haematology patients. Clonality was assessed by pulsed-field gel electrophoresis (PFGE) and automated ribotyping. Infection, requirement for intensive care unit (ICU) admission and all-cause 30-day mortality were used as clinical indicators of organism virulence. Forty-one VREfm vanB isolates (41 patients 14 infected and 27 colonised only) were analysed. Thirty-five of these isolates were typed by PFGE, 31 of which were represented by three clusters. The esp gene was identified in 22 of 27 (81.5%) screening and 11 of 14 (78.6%) infection-associated isolates. One isolate was hyl gene positive, and no isolate contained asa1, gel E or cylA genes. VREfm infection was independently associated with host factors (underlying diagnosis of acute myeloid leukaemia, age <or=60 years) but not with presence of the esp gene. ICU admission was negatively associated with presence of the esp gene (OR: 0.05 95% CI: 0.01-0.61 P=0.02). There was no association between 30-day mortality and host factors or the presence of the esp gene. When compared to European and US reports, a high esp gene prevalence and low hyl gene prevalence was observed in polyclonal VRE isolates obtained from this immunocompromised population.
Publisher: Informa UK Limited
Date: 23-07-2020
Publisher: Hindawi Limited
Date: 03-2011
DOI: 10.1111/J.1365-2354.2011.01238.X
Abstract: Diet is thought to account for about 25% of cancers in developed countries. It is well documented that the risks associated with both the breast cancer itself and its treatments are important for women previously treated for breast cancer. Women are at risk of recurrence of the primary disease and prone to develop treatment-induced co-morbidities, some of which are thought to be modified by diet. With a view to making dietary recommendations for the breast cancer patients we encounter in our clinical nursing research, we mined the literature to scope the most current robust evidence concerning the role of the diet in protecting women against the recurrence of breast cancer and its potential to ameliorate some of the longer-term morbidities associated with the disease. We found that the evidence about the role of the diet in breast cancer recurrence is largely inconclusive. However, drawing on international guidelines enabled us to make three definitive recommendations: women at risk of breast cancer recurrence, or who experience co-morbidities as a result of treatment, should limit their exposure to alcohol, moderate their nutritional intake so it does not contribute to post-menopausal weight gain, and should adhere to a balanced diet. Nursing education planned for breast cancer patients about dietary issues should ideally be in idually tailored, based on a good understanding of the international recommendations and the evidence underpinning them.
Publisher: Elsevier BV
Date: 07-2009
DOI: 10.1111/J.1469-0691.2009.02802.X
Abstract: Australia-wide population-based surveillance for scedosporiosis identified 180 cases, with 118 (65.6%) cases of colonization and 62 (34.4%) cases of infection. Predisposing factors for isolation of Scedosporium spp. included chronic lung disease in 37.8% and malignancy in 21.7% of cases. Predictors of invasive disease (n=62) included haematological stem cell transplantation (n=7), leukaemia (n=16) and diabetes mellitus (n=8). Of 183 phenotypically-speciated isolates, 75 (41%) were Scedosporium prolificans (risk factors: haematologic cancer (n=17), neutropaenia (n=14)) and 108 (59%) had Scedosporium apiospermum/Pseudallescheria boydii phenotype [risk factor: diabetes (n=15)]. Scedosporium prolificans (p 0.01) and leukaemia (p 0.03) independently predicted death. Epidemiological and antifungal susceptibility profiles of Scedosporium aurantiacum (prevalence>or=15.8%) and S. apiospermum were similar. No patient with S. aurantiacum infection (n=6) died. This is the first description of clinical features associated with S. aurantiacum.
Publisher: Oxford University Press (OUP)
Date: 2016
DOI: 10.1093/OFID/OFW153
Abstract: Antibiotic allergy testing (AAT) practices of Emerging Infections Network infectious disease physicians were surveyed. Although AAT was perceived to be necessary for removal of inappropriate or unnecessary allergy labels, there was limited access to any form of testing. In this study, we discuss current antibiotic allergy knowledge gaps and the development of AAT practices within antimicrobial stewardship programs, which will potentially improve antimicrobial prescribing.
Publisher: CSIRO Publishing
Date: 2011
DOI: 10.1071/AH10951
Abstract: Background. Adult febrile neutropenic oncology patients, at low risk of developing medical complications, may be effectively and safely managed in an ambulatory setting, provided they are appropriately selected and adequate supportive facilities and clinical services are available to monitor these patients and respond to any clinical deterioration. Methods. A cost analysis was modelled using decision tree analysis, published cost and effectiveness parameters for ambulatory care strategies and data from the State of Victoria’s hospital morbidity dataset. Two-way sensitivity analyses and Monte Carlo simulation were performed to evaluate the uncertainty of costs and outcomes associated with ambulatory care. Results. The modelled cost analysis showed that cost savings for two ambulatory care strategies were ~30% compared to standard hospital care. The weighted average cost saving per episode of ‘low-risk’ febrile neutropenia using Strategy 1 (outpatient follow-up only) was 35% (range: 7–55%) and that for Strategy 2 (early discharge and outpatient follow-up) was 30% (range: 7–39%). Strategy 2 was more cost-effective than Strategy 1 and was deemed the more clinically favoured approach. Conclusion. This study outlines a cost structure for a safe and comprehensive ambulatory care program comprised of an early discharge pathway with outpatient follow-up, and promotes this as a cost effective approach to managing ‘low-risk’ febrile neutropenic patients. What is known about the topic? Febrile neutropenia is a common complication of chemotherapy for patients with cancer. There is high level evidence supporting the use of ambulatory care strategies to manage patients with febrile neutropenia who are deemed to be at low risk of developing medical complications. What does this paper add? This paper highlights a cost structure for an adequately equipped and cost-effective ambulatory care strategy suitable for Australian hospitals to manage patients with low-risk febrile neutropenia. What are the implications for practitioners? The strategy advocated in this paper affords eligible patients the choice of early discharge from hospital. It advocates for improved resource utilisation and expansion of outpatient services in order to minimise opportunity costs faced by cancer treatment facilities.
Publisher: Elsevier BV
Date: 05-2016
DOI: 10.1016/J.IJANTIMICAG.2016.01.017
Abstract: Pristinamycin has been used to treat a range of Gram-positive infections, but reported experience in patients with malignancy is limited. This study aimed to evaluate the use of pristinamycin in patients with cancer at an Australian centre. All patients commenced on oral pristinamycin therapy at the Peter MacCallum Cancer Centre between January 2005 and December 2014 were identified using the hospital pharmacy dispensing system. Information on demographics, co-morbidities, cancer diagnosis, infection characteristics, pristinamycin regimen, pristinamycin tolerability and outcomes was collected. The median duration of follow-up was 398 days. In total, 26 patients received pristinamycin, with median age of 61 years and a male predominance (65%). Underlying diagnoses were haematological malignancies (50%) and solid tumours (50%). Pathogens included 13 meticillin-resistant Staphylococcus aureus, 6 vancomycin-resistant Enterococcus faecium, 4 meticillin-resistant Staphylococcus epidermidis, 2 meticillin-susceptible S. aureus and 1 vancomycin-susceptible E. faecium. Infection sites were osteomyelitis (6), skin and soft-tissue (4), intra-abdominal elvic abscess (4), bloodstream (3), empyema (3), endocarditis/endovascular (3), prosthesis-related infection (2) and epididymo-orchitis (1). One patient ceased pristinamycin due to nausea. Regarding outcome, 13 patients (50%) were cured of infection, 8 (31%) had suppression and 5 (19%) had relapse. Relapses included 1 endovascular infection, 2 episodes of osteomyelitis, 1 pelvic abscess and 1 skin and soft-tissue infection. Overall, 81% of patients achieved cure or suppression of antibiotic-resistant or complex Gram-positive infections, consistent with published experience in non-cancer populations. A favourable tolerability profile makes oral pristinamycin a viable treatment option, particularly in settings where outpatient management of cancer is the objective.
Publisher: Wiley
Date: 04-2006
DOI: 10.1111/J.1440-1797.2006.00554.X
Abstract: Opportunistic infections are a common and anticipated accompaniment of transplantation, but are generally somewhat predictable in their timing and epidemiology. The authors report here a case of miliary tuberculosis occurring within 3 weeks of transplantation, in a patient not expected to be significantly at risk, and with a normal chest X-ray at the time of transplantation. A 25-year-old Caucasian male dialysis patient who received two paediatric kidneys as an en bloc renal transplant developed fever 3 weeks following transplantation this eventually proved to be miliary tuberculosis. As well as antituberculous therapy and a significant reduction in the patient's conventional immunosuppression, intravenous immunoglobulin was used as anti-rejection prophylaxis. The case highlights the immunosuppressed status of dialysis patients prior to transplantation and the need for broad differential diagnosis in transplant recipients even in the absence of recognized epidemiological factors. The case also emphasizes the role of intravenous immunoglobulin as an anti-rejection therapy that does not add to the patient's immunosuppressive burden.
Publisher: Informa UK Limited
Date: 08-2010
Publisher: Springer Science and Business Media LLC
Date: 07-06-2019
DOI: 10.1007/S00259-018-4062-8
Abstract: Invasive fungal infections (IFIs) are common in immunocompromised patients. While early diagnosis can reduce otherwise high morbidity and mortality, conventional CT has suboptimal sensitivity and specificity. Small studies have suggested that the use of FDG PET/CT may improve the ability to detect IFI. The objective of this study was to describe the proven and probable IFIs detected on FDG PET/CT at our centre and compare the performance with that of CT for localization of infection, dissemination and response to therapy. FDG PET/CT reports for adults investigated at Peter MacCallum Cancer Centre were searched using keywords suggestive of fungal infection. Chart review was performed to describe the risk factors, type and location of IFIs, indication for FDG PET/CT, and comparison with CT for the detection of infection, and its dissemination and response to treatment. Between 2007 and 2017, 45 patients had 48 proven robable IFIs diagnosed prior to or following FDG PET/CT. Overall 96% had a known malignancy with 78% being haematological. FDG PET/CT located clinically occult infection or dissemination to another organ in 40% and 38% of IFI patients, respectively. Of 40 patients who had both FDG PET/CT and CT, sites of IFI dissemination were detected in 35% and 5%, respectively (p < 0.001). Of 18 patents who had both FDG PET/CT and CT follow-up imaging, there were discordant findings between the two imaging modalities in 11 (61%), in whom normalization of FDG avidity of a lesion suggested resolution of active infection despite a residual lesion on CT. FDG PET/CT was able to localize clinically occult infection and dissemination and was particularly helpful in demonstrating response to antifungal therapy.
Publisher: Elsevier BV
Date: 07-2018
Publisher: Elsevier BV
Date: 11-2016
DOI: 10.1016/J.EJCA.2016.07.025
Abstract: The objective of this review was to determine the impact of immunomodulatory drugs (IMiDs) and proteasome inhibitor (PI)-based therapy on infection risk in patients with myeloma across three treatment periods: induction, maintenance therapy and relapse/refractory disease (RRMM). A systematic review and meta-analysis of randomised controlled trials (RCT) of IMiD and PI-based therapy versus conventional therapy from 1990 to 2015 using MEDLINE, EMBASE and CENTRAL was conducted. Study methods, characteristics, interventions, outcomes and rate of infection were extracted using a standardised tool. Thirty RCTs of 13,105 patients fulfilled inclusion criteria. The rate of severe infection with the use of IMiD-based therapy was 13.4%, 22.4%, 10.5% and 16.6% for induction therapy for non-transplant- and transplant-eligible patients, maintenance therapy and therapy for RRMM, respectively. Rate of severe infection with PI-based induction in transplant-eligible patients was 19.7%. Compared to conventional therapy, use of IMiD-based induction therapy was associated with reduced risk for transplant patients (RR 0.76, p < 0.01). There was no significant difference with PI-based therapy. For maintenance therapy and RRMM, use of IMiD-based therapy was significantly associated with 74% and 51% increased risk of severe infection, respectively. Compared to thalidomide, bortezomib-based induction therapy and lenalidomide maintenance therapy were associated with increased risk of severe infection (RR 2.03, p < 0.01 RR 1.95, p = 0.03). The differential impact of myeloma therapies on risk for infection and the effect of treatment phases upon risk have now been established. Thalidomide is associated with the lowest risk of severe infection when used for induction and maintenance therapy. Fight Cancer Foundation.
Publisher: Wiley
Date: 07-2007
DOI: 10.1111/J.1399-3062.2007.00259.X
Abstract: The risk of recurrence or progression of prior invasive fungal infection, predominantly due to molds, is 11-33% during subsequent stem cell transplantations or myelosuppressive chemotherapy, with a high mortality. Risk factors at the time of transplant include active infection and having received <6 weeks of antifungal therapy, while after transplant prolonged neutropenia and graft-versus-host disease requiring aggressive immunosuppression are important. The use of peripheral blood stem cells has been associated with a lower risk. Minimal data are available regarding the role of preventative strategies such as surgical resection of pulmonary lesions and prophylactic granulocyte transfusions during neutropenia, the optimal duration of antifungal prophylaxis, and the appropriate monitoring strategy. This article critically evaluates these issues and provides recommendations for the secondary prophylaxis of invasive mold infections.
Publisher: BMJ
Date: 07-2018
DOI: 10.1136/BMJOQ-2018-000355
Abstract: Infection and sepsis are common problems in cancer management affecting up to 45% of patients and are associated with significant morbidity, mortality and healthcare utilisation. To develop and implement a whole of hospital clinical pathway for the management of sepsis (SP) in a specialised cancer hospital and to measure the impact on patient outcomes and healthcare utilisation. A multidisciplinary sepsis working party was established. Process mapping of practices for recognition and management of sepsis was undertaken across all clinical areas. A clinical pathway document that supported nurse-initiated sepsis care, prompt antibiotic and fluid resuscitation was implemented. Process and outcome measures for patients with sepsis were collected preimplementation (April–December 2012), postimplementation cohorts (April–December 2013), and from January to December 2014. 323 patients were evaluated (111 preimplementation, 212 postimplementation). More patients with sepsis had lactate measured (75.0% vs 17.2%) and appropriate first dose antibiotic (90.1% vs 76.1%) (all p .05). Time to antibiotics was halved (55 vs 110 min, p .05). Patients with sepsis had lower rates of intensive care unit admission (17.1% vs 35.5%), postsepsis length of stay (7.5 vs 9.9 days), and sepsis-related mortality (5.0% vs 16.2%) (all p .05). Mean total hospital admission costs were lower in the SP cohort, with a significant difference in admission costs between historical and SP non-surgical groups of $A8363 (95% CI 81.02 to 16645.32, p=0.048) per patient on the pathway. A second cohort of 449 patients with sepsis from January to December 2014 demonstrated sustained improvement. The SP was associated with significant improvement in patient outcomes and reduced costs. The SP has been sustained since 2013, and has been successfully implemented in another hospital with further implementations underway in Victoria.
Publisher: Oxford University Press (OUP)
Date: 27-01-2017
DOI: 10.1093/MMY/MYW141
Abstract: Empirical antifungal therapy is frequently used in hematology patients at high risk of invasive aspergillosis (IA), with substantial cost and toxicity. Biomarkers for IA aim for earlier and more accurate diagnosis and targeted treatment. However, data on the cost-effectiveness of a biomarker-based diagnostic strategy (BDS) are limited. We evaluated the cost effectiveness of BDS using results from a randomized controlled trial (RCT) and in idual patient costing data. Data inputs derived from a published RCT were used to construct a decision-analytic model to compare BDS (Aspergillus galactomannan and PCR on blood) with standard diagnostic strategy (SDS) of culture and histology in terms of total costs, length of stay, IA incidence, mortality, and years of life saved. Costs were estimated for each patient using hospital costing data to day 180 and follow-up for survival was modeled to five years using a Gompertz survival model. Treatment costs were determined for 137 adults undergoing allogeneic hematopoietic stem cell transplant or receiving chemotherapy for acute leukemia in four Australian centers (2005-2009). Median total costs at 180 days were similar between groups (US$78,774 for SDS [IQR US$50,808-123,476] and US$81,279 for BDS [IQR US$59,221-123,242], P = .49). All-cause mortality was 14.7% (10/68) for SDS and 10.1% (7/69) for BDS, (P = .573). The costs per life-year saved were US$325,448, US$81,966, and US$3,670 at 180 days, one year and five years, respectively. BDS is not cost-sparing but is cost-effective if a survival benefit is maintained over several years. An in idualized institutional approach to diagnostic strategies may maximize utility and cost-effectiveness.
Publisher: Wiley
Date: 2021
DOI: 10.1002/CTI2.1235
Publisher: Informa UK Limited
Date: 21-09-2016
DOI: 10.1080/14787210.2016.1234376
Abstract: Clostridium difficile infection (CDI) is a significant cause of healthcare-associated diarrhoea, and the emergence of endemic strains resulting in poorer outcomes is recognised worldwide. Patients with cancer are a specific high-risk group for development of infection. Areas covered: In this review, modifiable and non-modifiable risk factors for CDI in adult patients with haematological malignancy or solid tumours are evaluated. In particular, the contribution of antimicrobial exposure, hospitalisation and gastric acid suppression to risk of CDI are discussed. Recent advances in CDI treatment are outlined, namely faecal microbiota transplantation and fidaxomicin therapy for severe/refractory infection in cancer populations. Outcomes of CDI, including mortality are presented, together with the need for valid severity rating tools customised for cancer populations. Expert commentary: Future areas for research include the prognostic value of C. difficile colonisation in cancer patients and the potential impact of dedicated antimicrobial stewardship programs in reducing the burden of CDI in cancer units.
Publisher: Oxford University Press (OUP)
Date: 30-10-2015
DOI: 10.1093/JAC/DKV343
Abstract: The primary objectives were to investigate the prescribing practices of primary antifungal prophylaxis (PAP) and incidence of invasive fungal disease (IFD) in adult patients with ALL receiving induction-consolidation chemotherapy. Secondary objectives were to determine risk factors for IFD and resource utilization associated with IFD. A retrospective chart review of adult patients with ALL from commencement of induction until completion of consolidation chemotherapy was undertaken from January 2008 to June 2013 in four hospitals in Melbourne, Australia. IFD was classified according to the revised European Organisation for Research and Treatment of Cancer criteria. Cost analysis was performed from an Australian public hospital perspective. Ninety-eight patients were included in the audit 83 (85%) received PAP. Most patients (49/83, 59%) switched between two different antifungal agents, predominantly between liposomal hotericin B and an azole. Five proven robable and six possible IFD cases were identified. Proven robable IFD was most common in patients receiving the BFM95 chemotherapy protocol. The incidence of proven robable IFD was significantly lower in patients receiving PAP compared with those who did not (2/78, 2.6% versus 3/14, 21.4% P = 0.024). For every five patients receiving PAP, one proven robable IFD case would be prevented. Proven robable IFD was associated with an additional median cost of 121,520 Australian dollars (95% CI: 90,781-180,141 Australian dollars P < 0.001) compared with patients without IFD. This is the first multicentre study evaluating PAP use in patients with ALL. With the caveats of interpretation of retrospective, non-randomized data, PAP was associated with a reduced IFD risk.
Publisher: Informa UK Limited
Date: 17-12-2020
Publisher: Oxford University Press (OUP)
Date: 05-2011
DOI: 10.3109/13693786.2010.551426
Abstract: Endemic mycoses are important fungal infections in their respective habitats. In the Asia-Pacific region, an accurate epidemiological picture of endemic mycoses is elusive few epidemiological surveys have been performed, and limited laboratory facilities and experience with fungal infections have further h ered recognition of infection. However, pockets of endemicity do indeed exist, and endemic fungal infections can have a significant impact on public health. This article reviews the most common endemic mycoses in the Asia-Pacific region: histoplasmosis, penicilliosis, and sporotrichosis. Blastomycosis, which has been infrequently reported within the region, is also briefly discussed. Certain areas of the Asia-Pacific region are endemic for histoplasmosis however, the ecologic niche for this infection remains unclear. Penicilliosis is restricted to Southeast and Eastern Asia, whereas sporotrichosis is encountered in tropical areas of the Asia-Pacific region linked to environmental reservoirs distinct from those seen in the Western world. Before the advent of acquired immune deficiency syndrome (AIDS), histoplasmosis and penicilliosis were only occasionally reported however, the incidence of both mycoses has increased with the rise in the incidence of AIDS. Comprehensive studies are needed to fully assess the areas of endemicity and the impact of endemic mycoses in the Asia-Pacific region.
Publisher: Informa UK Limited
Date: 2001
DOI: 10.3109/10428190109097768
Abstract: We describe a case of successfully treated multifocal pulmonary Rhizomucor pusillus, a condition which has previously been universally fatal. A 77 year-old man had a background of chronic neutropenia due to hairy-cell leukemia, splenectomy, corticosteroid therapy and an obstructing left ureteric transitional-cell carcinoma. He was successfully treated with 3 months of high-dose liposomal hotericin B and 7 months of granulocyte-macrophage colony-stimulating factor. Treatment was complicated by mild reversible deterioration of renal function. There was a near complete radiological response to the therapy at 6 months and the patient remains well 20 months following diagnosis of R. pusillus and 13 months following cessation of treatment.
Publisher: Wiley
Date: 2011
DOI: 10.1111/J.1445-5994.2010.02341.X
Abstract: The use of oral prophylactic antibiotics in patients with neutropenia is controversial and not recommended by this group because of a lack of evidence showing a reduction in mortality and concerns that such practice promotes antimicrobial resistance. Recent evidence has demonstrated non-significant but consistent, improvement in all-cause mortality when fluoroquinolones (FQs) are used as primary prophylaxis. However, the consensus was that this evidence was not strong enough to recommend prophylaxis. The evidence base for FQ prophylaxis is presented alongside current consensus opinion to guide the appropriate and judicious use of these agents. Due consideration is given to patient risk, as it pertains to specific patient populations, as well as the net effect on selective pressure from antibiotics if FQ prophylaxis is routinely used in a target population. The potential costs and consequences of emerging FQ resistance, particularly among Escherichia coli, Clostridium difficile and Gram-positive organisms, are considered. As FQ prophylaxis has been advocated in some chemotherapy protocols, specific regard is given to whether FQ prophylaxis should be used to support these regimens. The group also provides recommendations for monitoring and surveillance of emerging resistance in those centres that have adopted FQ prophylaxis.
Publisher: Elsevier BV
Date: 06-2020
Publisher: Wiley
Date: 14-09-2023
DOI: 10.1111/TID.14154
Publisher: Springer Science and Business Media LLC
Date: 13-06-2017
DOI: 10.1038/BJC.2017.154
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2010
Publisher: Oxford University Press (OUP)
Date: 15-06-2012
DOI: 10.1634/THEONCOLOGIST.2011-0456
Abstract: After completing this course, the reader will be able to: Identify fever and neutropenia in a cancer patient as a medical emergency requiring prompt assessment and antibiotic therapy.Explain the use of risk assessment scores to determine the risk of complications of fever and neutropenia at presentation. CME This article is available for continuing medical education credit at CME.TheOncologist.com To examine the clinical characteristics and financial charges associated with treating adult cancer patients receiving chemotherapy in outpatient clinics who presented to the emergency department (ED) with neutropenia. A retrospective audit was conducted across two health services involving ED episodes and subsequent hospital admissions of patients who received chemotherapy through day oncology from January 1 to December 31, 2007 and presented to the ED with neutropenia. ED data were collected from the Victorian Emergency Minimum Dataset and charges were collected from Health Information Services. Descriptive and bivariate statistics were used to describe the patient and clinical characteristics and financial outcomes, and to explore associations between these factors. In total, 200 neutropenic episodes in 159 outpatients were seen in the ED over the survey period. The mean patient age was 56.6 years (standard deviation, 13.2 years) and 47.2% were male. Overall, 70.0% of ED episodes were triaged as Australasian Triage Scale 2 (emergency). The median ED wait time was 10 minutes and the median ED length of stay was 6.8 hours. The median charge for each ED episode was $764.08 Australian dollars. The total combined ED and inpatient charge per episode was in the range of $144.27–$174,732.68, with a median charge of $5,640.87. This study provides important insights into the clinical and economic burden of neutropenia from both the ED and inpatient perspectives. Alternative treatment models, such as outpatient treatment, early discharge programs or prophylactic interventions to reduce the clinical and economic burden of neutropenia on our health system, must be explored.
Publisher: Springer Science and Business Media LLC
Date: 08-02-2017
DOI: 10.1007/S00204-016-1916-3
Abstract: The echinocandins-caspofungin, anidulafungin and micafungin-are semi-synthetic cyclic hexapeptide antimicrobial agents with modified N-linked acyl lipid side chains which anchor the compounds to the phospholipid bilayer of the fungal cell membrane, thereby inhibiting synthesis of fungal cell wall glucan. Over the last 10 years, echinocandins have become the first-line antifungal treatment of candidaemia and other forms of invasive candidiasis (IC). Echinocandins are generally well tolerated, but their use is limited by their requirement for daily intravenous dosing, lack of oral formulation and limited spectrum. In critically ill patients, it is also recognised that achievement of their pharmacokinetic harmacodynamic targets shows large inter-in idual variability. As a drug class, they are safe to use and are associated with few adverse reactions and few drug-drug interactions of significance. Recent discovery of their ability to prevent and treat Candida biofilm formation particularly in the presence of invasive medical devices and also their ability to penetrate into mucosal surfaces such as vulvovaginal candidiasis has opened up new opportunities for research into their drug delivery. New dosing intervals are being explored to allow less frequent intravenous dosing in the ambulatory setting, and a new long-acting echinocandin, CD101, is being developed for weekly and topical administration.
Publisher: Elsevier BV
Date: 05-2009
DOI: 10.1016/J.ATHORACSUR.2009.02.069
Abstract: The purpose of this study was to analyze our institutional results with pulmonary resection in neutropenic patients with hematologic malignancies and suspected invasive pulmonary fungal infections. We performed a retrospective medical record review of 25 immunocompromised patients with hematologic malignancies who underwent pulmonary resection between 2000 and 2007. We analyzed preoperative diagnostic technique, degree of pulmonary resection, and postoperative morbidity and mortality to determine whether surgery is a viable treatment option in this subset of patients. Twenty-three of 25 patients had a minithoracotomy compared with 2 who had video-assisted thorascopic surgery resection only. Thirteen had wedge resections, 9 had lobectomies, and 3 had segmentectomies. Early surgical morbidity was 2 of 25, involving 1 pneumothorax and 1 empyema. In-hospital mortality was 2, with 1 death primarily related to surgery. Median survival was 342 days, and survival was significantly better in patients with only one lesion. No patient experienced late recurrence of invasive pulmonary fungal infection. Resected pulmonary tissue also provided the best chance for a proven diagnosis in 19 of 25 (76%). This study confirms that pulmonary resection in high-risk immunocompromised patients with suspected invasive fungal infection can be carried out with excellent operative morbidity and mortality.
Publisher: Oxford University Press (OUP)
Date: 05-06-2012
DOI: 10.1093/CID/CIS529
Abstract: Longer-term morbidity and outcomes of Cryptococcus gattii infection are not described. We analyzed clinical, microbiological, and outcome data in Australian patients followed for 12 months, to identify prognostic determinants. Culture-confirmed C. gattii cases from 2000 to 2007 were retrospectively evaluated. Clinical, microbiological, radiological, and outcome data were recorded at diagnosis and at 6 weeks, 6 months, and 12 months. Clinical and laboratory variables associated with mortality and with death and/or neurological sequelae were determined. Annual C. gattii infection incidence was 0.61 per 10(6) population. Sixty-two of 86 (72%) patients had no immunocompromise 6 of 24 immunocompromised hosts had idiopathic CD4 lymphopenia, and 1 had human immunodeficiency virus/AIDS. Clinical and microbiological characteristics of infection were similar in immunocompromised and healthy hosts. Isolated lung, combined lung and central nervous system (CNS), and CNS only disease was reported in 12%, 51% and 34% of the cases, respectively. Complications in CNS disease included raised intracranial pressure (42%), hydrocephalus (30%), neurological deficits (27% 6% developed during therapy) and immune reconstitutionlike syndrome (11%). Geometric mean serum cryptococcal antigen (CRAG) titers in CNS disease were 563.9 (vs 149.3 in isolated lung infection). Patient immunocompromise was associated with increased mortality risk. An initial cerebrospinal fluid CRAG titer of ≥256 predicted death and/or neurological sequelae (P = .05). Neurological C. gattii disease predominates in the Australian endemic setting. Lumbar puncture and cerebral imaging, especially if serum CRAG titers are ≥512, are essential. Long-term follow up is required to detect late neurological complications. Immune system evaluation is important because host immunocompromise is associated with reduced survival.
Publisher: Springer Science and Business Media LLC
Date: 12-03-2021
DOI: 10.1186/S12912-021-00560-Z
Abstract: Hospital and university service providers invest significant but separate resources into preparing registered nurses to work in the emergency department setting. This results in the duplication of both curricula and resource investment in the health and higher education sectors. This paper describes an evidence-based co-designed study with clinical-academic stakeholders from hospital and university settings. The study was informed by evidence-based co-design, using emergency nursing as an exemplar. Eighteen hours of co-design workshops were completed with 21 key clinical-academic stakeholders from hospital and university settings. Outcomes were matrices synchronising professional and regulatory imperatives of postgraduate nursing coursework mutually-shaped curriculum content, teaching approaches and assessment strategies relevant for postgraduate education a new University-Industry Academic Integration Framework five agreed guiding principles of postgraduate curriculum development for university-industry curriculum co-design and a Graduate Certificate of Emergency Nursing curriculum exemplar. Industry-academic service provider co-design can increase the relevance of postgraduate specialist courses in nursing, strengthening the nexus between both entities to advance learning and employability. The study developed strategies and exemplars for future use in any mutually determined academic-industry education partnership.
Publisher: Springer Science and Business Media LLC
Date: 11-2003
Publisher: Oxford University Press (OUP)
Date: 18-03-2022
DOI: 10.1093/JAC/DKAC060
Abstract: Invasive fungal disease (IFD) remains a common and serious complication in children treated for leukaemia. Antifungal prescription in children with leukaemia presents unique challenges, particularly due to variation in IFD risk between and within leukaemia treatment protocols, drug toxicities and interactions between antifungals and chemotherapeutic agents. With recent advances in the understanding of IFD epidemiology and large clinical trials in adults assessing antifungals for IFD treatment and prophylaxis, together with paediatric clinical and pharmacokinetic studies, there is a growing body of data to inform optimal antifungal use in children. A panel of infectious diseases and haematology-oncology clinicians with expertise in IFD management compiled a list of 10 key clinical questions following development of the 2021 Australia and New Zealand Mycology Antifungal Consensus Guidelines. A focused literature review was conducted to explore available evidence and identify gaps in knowledge to direct future research. With the changing epidemiology of IFD globally, the ongoing evolution of paediatric leukaemia treatment and the increasing availability of novel antifungal agents, advocacy for paediatric clinical studies will remain vital to optimize IFD prevention and treatment in children with leukaemia.
Publisher: Oxford University Press (OUP)
Date: 11-11-2020
DOI: 10.1093/CID/CIAA1711
Abstract: Seroprotection and seroconversion rates are not well understood for 2-dose inactivated influenza vaccination (IIV) schedules in autologous hematopoietic stem cell transplantation (autoHCT) patients. A randomized, single-blind, controlled trial of IIV in autoHCT patients in their first year post-transplant was conducted. Patients were randomized 1:1 to high-dose (HD) IIV followed by standard dose (SD) vaccine (HD-SD arm) or 2 SD vaccines (SD-SD arm) 4 weeks apart. Hemagglutination inhibition (HI) assay for IIV strains was performed at baseline, 1, 2, and 6 months post–first dose. Evaluable primary outcomes were seroprotection (HI titer ≥40) and seroconversion (4-fold titer increase) rates and secondary outcomes were geometric mean titers (GMTs), GMT ratios (GMRs), adverse events, influenza-like illness (ILI), and laboratory-confirmed influenza (LCI) rates and factors associated with seroconversion. Sixty-eight patients were enrolled (34/arm) with median age of 61.5 years, majority male (68%) with myeloma (68%). Median time from autoHCT to vaccination was 2.3 months. For HD-SD and SD-SD arms, percentages of patients achieving seroprotection were 75.8% and 79.4% for H1N1, 84.9% and 88.2% for H3N2 (all P & .05), and 78.8% and 97.1% for influenza-B/Yamagata (P = .03), respectively. Seroconversion rates, GMTs and GMRs, and number of ILI or LCIs were not significantly different between arms. Adverse event rates were similar. Receipt of concurrent cancer therapy was independently associated with higher odds of seroconversion (OR, 4.3 95% CI, 1.2–14.9 P = .02). High seroprotection and seroconversion rates against all influenza strains can be achieved with vaccination as early as 2 months post-autoHCT with either 2-dose vaccine schedules. Australian New Zealand Clinical Trials Registry: ACTRN12619000617167.
Publisher: Springer Science and Business Media LLC
Date: 24-03-2021
Publisher: Oxford University Press (OUP)
Date: 30-04-2014
DOI: 10.1093/JAC/DKU124
Abstract: Species-specific clinical breakpoints (CBPs) for Candida spp. were established following consideration of clinical outcomes in patients with oesophageal candidiasis. We sought to further determine the validity of the current CBPs based on data from a prospective candidaemia study. All Candida albicans candidaemia episodes in patients enrolled in the Australian Candidaemia Study and who were treated with fluconazole monotherapy were included. Fluconazole MICs were established using Sensititre(®) YeastOne(®). Two hundred and seventeen evaluable episodes were identified, 93.5% of which occurred in adult patients. Fluconazole was commenced within 72 h of blood culture positivity in 96.3% (209/217) of episodes. Fluconazole doses were appropriate in 89.9% (195/217) of episodes and the median duration of therapy was 14 days (IQR 8-21 days) for the whole cohort. The all-cause 30 day mortality was 19.8% (43/217), with 37.2% (16/43) of deaths attributed to candidaemia. Classification and regression tree (CART) analysis identified a fluconazole MIC target of ≥2 mg/L for infection-related mortality and ≥4 mg/L for overall 30 day mortality. Overall mortality was no different in episodes with isolates above or below the identified MIC target, although there was a trend towards significance (P = 0.051). On univariate analysis, infection-related mortality was significantly increased in C. albicans episodes with an MIC ≥2 mg/L compared with those below this MIC target (20.6% versus 4.9% P = 0.001). This target remained an independent predictor of infection-related mortality (OR 8.2 95% CI 2.3-29.7 P = 0.001). We observed a direct relationship between infection-related mortality and rising fluconazole MIC for C. albicans candidaemia overall, the data support the EUCAST and revised CLSI fluconazole clinical breakpoints.
Publisher: Oxford University Press (OUP)
Date: 08-11-2016
DOI: 10.1093/JAC/DKW422
Abstract: Knowledge of contemporary epidemiology of candidaemia is essential. We aimed to identify changes since 2004 in incidence, species epidemiology and antifungal susceptibilities of Candida spp. causing candidaemia in Australia. These data were collected from nationwide active laboratory-based surveillance for candidaemia over 1 year (within 2014-2015). Isolate identification was by MALDI-TOF MS supplemented by DNA sequencing. Antifungal susceptibility testing was performed using Sensititre YeastOne™. A total of 527 candidaemia episodes (yielding 548 isolates) were evaluable. The mean annual incidence was 2.41/105 population. The median patient age was 63 years (56% of cases occurred in males). Of 498 isolates with confirmed species identity, Candida albicans was the most common (44.4%) followed by Candida glabrata complex (26.7%) and Candida parapsilosis complex (16.5%). Uncommon Candida species comprised 25 (5%) isolates. Overall, C. albicans (>99%) and C. parapsilosis (98.8%) were fluconazole susceptible. However, 16.7% (4 of 24) of Candida tropicalis were fluconazole- and voriconazole-resistant and were non-WT to posaconazole. Of C. glabrata isolates, 6.8% were resistant/non-WT to azoles only one isolate was classed as resistant to caspofungin (MIC of 0.5 mg/L) by CLSI criteria, but was micafungin and anidulafungin susceptible. There was no azole/echinocandin co-resistance. We report an almost 1.7-fold proportional increase in C. glabrata candidaemia (26.7% versus 16% in 2004) in Australia. Antifungal resistance was generally uncommon, but azole resistance (16.7% of isolates) amongst C. tropicalis may be emerging.
Publisher: Springer Science and Business Media LLC
Date: 04-2014
DOI: 10.1186/CC14056
Publisher: Informa UK Limited
Date: 03-05-2011
Publisher: Wiley
Date: 2007
Publisher: Wiley
Date: 2011
DOI: 10.1111/J.1445-5994.2010.02338.X
Abstract: The current consensus guidelines were developed to standardize the clinical approach to the management of neutropenic fever in adult cancer patients throughout Australian treating centres. The three areas of clinical practice covered by the guidelines, the process for developing consensus opinion, and the system used to grade the evidence and relative strength of recommendations are described. The health economics implications of establishing clinical guidance are also discussed.
Publisher: Springer Science and Business Media LLC
Date: 2011
Publisher: American Society of Clinical Oncology (ASCO)
Date: 20-03-2013
Publisher: Elsevier BV
Date: 08-2009
DOI: 10.1016/J.MIMET.2009.06.003
Abstract: A recently developed CSP typing scheme and proposed nomenclature was applied to a collection of 164 clinical and environmental Aspergillus fumigatus isolates from Melbourne, Australia. Fifteen CSP variants were observed overall, including three that were not reported in the original nomenclature that described 19 CSP variants, raising the possibility of phylogeographic differences between the Australian and the previously studied European and North American A. fumigatus populations. However, those CSP variants that were common between this and the previous studies appeared to have a broadly similar prevalence. The presence of an additional CCT codon in the 3' flanking region of some CSP variants was also observed in homologous Neosartorya fischeri sequence, suggesting that the absence of this codon in other isolates is due to codon deletion, rather than its presence representing a duplication. We recommend a number of modifications to the proposed CSP type nomenclature to accommodate these new findings.
Publisher: Oxford University Press (OUP)
Date: 12-05-2014
DOI: 10.1093/CID/CIU153
Publisher: Informa UK Limited
Date: 05-04-2019
DOI: 10.1080/10428194.2019.1590571
Abstract: PET/CT is useful for investigation of neutropenic fever (NF) and potential invasive fungal infection (IFI) in those with hematological malignancies (HM). An online survey evaluating the utility and current practices regarding PET/CT scanning for investigation of NF was distributed to infectious diseases (ID) clinicians and hematologists via email lists hosted by key professional bodies. One-hundred and forty-five clinicians responded (120 ID 25 hematologists). Access to PET/CT was fair but timeliness of investigation was limited (within 3 days in 35% and 46% of ID and hematology respondents, respectively). Among those with experience with PET/CT for infection (
Publisher: Wiley
Date: 20-04-2011
DOI: 10.1111/J.1365-2141.2011.08650.X
Abstract: Antifungal prophylaxis during treatment for haematological malignancies has been studied for 50 years, yet it has not been wholly effective even when using antifungal drugs that exhibit potent activity in vitro against a broad range of fungal pathogens. Trials have demonstrated that it can reduce the incidence of invasive fungal diseases (IFD) and fungal deaths, but only two studies have had an impact on overall mortality. Furthermore, it has not significantly reduced the need for empirical antifungal therapy. Posaconazole was effective in preventing invasive aspergillosis in two studies of high-risk patients, and consensus guidelines grade it as a suitable choice for antifungal prophylaxis of invasive mould disease however, its bioavailability was compromised by vomiting or diarrhoea so that an alternative parenteral antifungal drug was required. A recent trial of voriconazole prophylaxis after allogeneic stem cell transplantation failed to show superiority over fluconazole. With more accurate definitions of IFD, that utilize fungal biomarkers, such as galactomannan, together with computerized tomographic imaging, there is growing interest in a diagnostic-driven strategy, which could prove to be a more efficacious approach.
Publisher: Wiley
Date: 30-04-2018
DOI: 10.1002/PON.4728
Abstract: This paper examines the direct and intermediary relationships between life stress, stress appraisal, and resilience, and increased anxiety and depressive symptoms in Australian women after cancer treatment. Data examined from 278 women aged 18 years and older previously treated for breast, gynaecological, or blood cancer, participating in the Australian Women's Wellness after Cancer Program. Serial mediation models interrogated the effect of stressful life events (List of Threatening Experiences-Modified) mediated by appraisal and coping (Perceived Stress Scale and Connor-Davidson Resilience Scale), on symptoms of anxiety and depression (Zung Self-rating Anxiety Scale and Center for Epidemiologic Studies Depression Scale). Over one-quarter (30.2%) of participants reported 1 or more stressful life events, other than their cancer, in the previous 6 months. Results indicate that perceived stress fully mediated the relationships between life stress, anxiety (indirect effect = 0.09, Bias-corrected bootstrap 95% CI 0.02-0.18, Percent mediation = 0.51), and depressive symptoms (indirect effect = 0.11, Bias-corrected bootstrap 95% CI 0.02-0.23, Percent mediation = 0.71) and accounted for more than half of the relationship between predictor and outcome. Findings indicate that stress appraisal mediated the relationship between past life stressors and anxiety and depressive symptoms. This analysis also highlights the need to consider wellness within a broader care context to identify potentially vulnerable patients to possibly avert future health concerns.
Location: United States of America
Location: South Africa
Start Date: 2007
End Date: 2010
Funder: Pfizer
View Funded ActivityStart Date: 2005
End Date: 2005
Funder: Schering-Plough
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End Date: 2005
Funder: Gilead Sciences
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End Date: 2021
Funder: National Health and Medical Research Council
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End Date: 2019
Funder: National Health and Medical Research Council
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End Date: 2008
Funder: National Health and Medical Research Council
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End Date: 2020
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2009
End Date: 2012
Funder: Cancer Council NSW
View Funded ActivityStart Date: 2016
End Date: 2018
Funder: University of Melbourne
View Funded ActivityStart Date: 2003
End Date: 2003
Funder: Australian Commission on Safety and Quality in Health Care
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End Date: 2004
Funder: Department of Health, State Government of Victoria
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End Date: 2004
Funder: Pfizer Australia
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End Date: 1998
Funder: Bristol-Myers Squibb
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End Date: 2010
Funder: Royal Melbourne Hospital
View Funded ActivityStart Date: 2011
End Date: 2011
Funder: Jack Brockhoff Foundation
View Funded ActivityStart Date: 2003
End Date: 2008
Funder: National Health and Medical Research Council
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