ORCID Profile
0000-0002-9457-8262
Current Organisations
Universiti Sains Malaysia
,
Children's Hospital at Westmead
,
University of Sydney
,
Westmead Hospital
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Publisher: WHO Press
Date: 19-04-2010
Publisher: Springer Nature Singapore
Date: 2023
Publisher: Springer Nature Singapore
Date: 2023
Publisher: Elsevier BV
Date: 03-2016
Publisher: Informa UK Limited
Date: 10-2020
DOI: 10.2147/IJN.S269214
Publisher: Springer Science and Business Media LLC
Date: 28-07-2018
DOI: 10.1007/S00228-018-2525-2
Abstract: Audit studies reveal frequent non-compliance with dosing and monitoring guidelines for vancomycin. This study aimed to qualitatively explore the barriers and facilitators of compliance with vancomycin dosing and monitoring guidelines. Interviews were conducted with 16 prescribers in a large tertiary teaching hospital in Sydney, Australia. Questions explored knowledge, attitudes, and perceived complexities associated with vancomycin use. Interviews were analysed using thematic analysis. Prescribers reported utilising vancomycin guidelines, citing familiarity with guidelines, a positive perception of guidelines, awareness of poor guideline compliance, and assistance from specialist staff as facilitators of the uptake of guideline recommendations. Barriers existing within the prescribing environment such as the prescribing culture, a lack of time, and poor communication and coordination of therapeutic drug monitoring processes were identified as hindrances to guideline compliance. The provision of guidelines may not be sufficient in ensuring appropriate prescribing and monitoring of vancomycin when barriers relating to the prescribing environment exist. Developing interventions targeted toward these barriers, such as having dedicated phlebotomists for vancomycin blood s ling, fostering better handover processes, and educating staff on poorly understood aspects of guidelines, is likely to improve the uptake of guideline recommendations for vancomycin and other medications requiring therapeutic drug monitoring.
Publisher: Therapeutic Guidelines Limited
Date: 02-04-2019
Publisher: Oxford University Press (OUP)
Date: 10-07-2017
DOI: 10.1093/JAC/DKX209
Abstract: To determine the existence of concentration-toxicity relationships for common β-lactam antibiotic adverse effects and define thresholds above which toxicity is more likely. Retrospective review of consecutive patients treated with piperacillin, meropenem or flucloxacillin who underwent therapeutic drug monitoring (TDM) at St Vincent's Hospital (Sydney, Australia) between January 2013 and December 2015. Adverse events investigated included neurotoxicity, nephrotoxicity, hepatotoxicity and opportunistic Clostridium difficile infection. Toxicity was measured using observational grading criteria, clinical assessment and relevant serum biomarkers. These findings were correlated with trough TDM measurements at the time of toxicity presentation. TDM results from 378 patients (piperacillin = 223, meropenem = 94 and flucloxacillin = 61) were investigated. There was no difference in baseline patient characteristics across antibiotic groups. A statistically significant elevation in mean serum trough concentrations (Cmin) was found in patients diagnosed with neurotoxicity (piperacillin, P < 0.01 meropenem, P = 0.04 flucloxacillin, P = 0.01) and those who developed nephrotoxicity whilst being treated with piperacillin (P < 0.01) or meropenem (P 361.4 mg/L meropenem, Cmin >64.2 mg/L flucloxacillin, Cmin >125.1 mg/L) or nephrotoxicity (piperacillin, Cmin >452.65 mg/L meropenem, Cmin >44.45 mg/L) varied across antibiotics. Our data reveal an association between toxic concentrations for a number of β-lactam agents and neurotoxic/nephrotoxic effects. We have defined threshold concentrations above which these toxicities become more likely. Clinicians should balance concerns for therapeutic efficacy with potential toxicity when considering aggressive therapy.
Publisher: Springer Science and Business Media LLC
Date: 27-02-2021
Publisher: Wiley
Date: 03-2016
DOI: 10.1002/JPPR.1155
Publisher: Elsevier BV
Date: 03-2018
Publisher: Elsevier BV
Date: 2012
Publisher: Wiley
Date: 04-2020
DOI: 10.5694/MJA2.50355
Abstract: Bacteriophage (phage) therapy is re-emerging a century after it began. Activity against antibiotic-resistant pathogens and a lack of serious side effects make phage therapy an attractive treatment option in refractory bacterial infections. Phages are highly specific for their bacterial targets, but the relationship between in vitro activity and in vivo efficacy remains to be rigorously evaluated. Pharmacokinetic and pharmacodynamic principles of phage therapy are generally based on the classic predator-prey relationship, but numerous other factors contribute to phage clearance and optimal dosing strategies remain unclear. Combinations of fully characterised, exclusively lytic phages prepared under good manufacturing practice are limited in their availability. Safety has been demonstrated but randomised controlled trials are needed to evaluate efficacy.
Publisher: Oxford University Press (OUP)
Date: 14-05-2015
DOI: 10.1093/JAC/DKV124
Publisher: American Society for Microbiology
Date: 17-02-2021
DOI: 10.1128/AAC.01554-20
Abstract: The efficacy of fluconazole is related to the area under the plasma concentration-time curve (AUC) over the MIC of the microorganism. Physiological changes in critically ill patients may affect the exposure of fluconazole, and therefore dosing adjustments might be needed.
Publisher: MDPI AG
Date: 16-05-2022
DOI: 10.3390/ANTIBIOTICS11050670
Abstract: This prospective study aimed to explore the determinants of meropenem trough concentration (Ctrough) in patients with bacterial pneumonia and to investigate the association between its concentration and efficacy. From January 2019 to December 2019, patients with pulmonary infections were prospectively enrolled from the intensive care unit. Factors affecting the meropenem trough concentration were analyzed, and a multiple linear regression model was constructed. Logistic regression analyses were used to investigate the relationship between Ctrough and clinical efficacy. A total of 64 patients were enrolled, in whom 210 meropenem concentrations were measured. Of the total, 60.9% (39/64) were considered clinically successful after treatment. Ctrough may increase with increased blood urea nitrogen, albumin, and concomitant antifungal use. By contrast, concentration may decrease with increased endogenous creatinine clearance rate. Six variables, including Ctrough/minimum inhibitory concentration (MIC) 4, were associated with the efficacy of meropenem. There was an independent correlation between Ctrough/MIC 4 and efficacy after fully adjusting for confounding factors. Based upon renal function indexes, it is possible to predict changes in meropenem concentration and adjust the dosage precisely and in idually. Ctrough/MIC 4 is a potential instrument to predict successful treatment with meropenem.
Publisher: Springer Science and Business Media LLC
Date: 21-04-2023
Publisher: Springer Science and Business Media LLC
Date: 17-08-2018
DOI: 10.1007/S10096-018-3357-9
Abstract: To determine whether target concentration non-attainment can be anticipated in critically ill patients prior to initiating empiric β-lactam antibiotic therapy based on readily available clinical factors. Retrospective review of consecutive patients treated with piperacillin or meropenem and who underwent therapeutic drug monitoring (TDM) at St Vincent's Hospital (Sydney, Australia) between January 2013 and December 2015 was performed. Predefined subgroups were patients who received continuous renal replacement therapy (CRRT) and those who did not (non-CRRT). Potential risk factors were evaluated by correlation with β-lactam antibiotic trough concentrations (C
Publisher: Wiley
Date: 14-04-2021
DOI: 10.1111/BCP.14834
Abstract: Despite the availability of international consensus guidelines, vancomycin dosing and therapeutic drug monitoring (TDM) remain suboptimal. This study aimed to assess concordance of vancomycin dosing and TDM with institutional guidelines and to identify factors taken into consideration by clinicians when prescribing vancomycin. A retrospective audit of 163 patients receiving vancomycin therapy (≥48 hours) was undertaken. Data collected included patient characteristics, dosing history and plasma vancomycin and creatinine concentrations. Concordance of dosing and TDM with institutional guidelines was evaluated. Semi‐structured interviews, including simulated prescribing scenarios, were undertaken with prescribers ( n = 17) and transcripts analysed. Plasma vancomycin concentrations ( n = 1043) were collected during 179 courses of therapy. Only 24% of courses commenced with a loading dose with 72% lower than recommended. The initial maintenance dose was concordant in 42% of courses with 34% lower than recommended. Only 14% of TDM s les were trough vancomycin concentrations. Dose was not adjusted for 60% (21/35) of subtherapeutic and 43% (18/42) of supratherapeutic trough vancomycin concentrations, respectively. Interview participants reported that patient characteristics (including renal function), vancomycin concentrations, guidelines and expert advice influenced vancomycin prescribing decisions. Despite referring to guidelines when completing simulated prescribing scenarios, only 37% of prescribing decisions aligned with guideline recommendations. Poor compliance with institutional vancomycin guidelines was observed, despite prescriber awareness of available guidelines. Multifaceted strategies to support prescriber decision‐making are required to improve vancomycin dosing and monitoring.
Publisher: Elsevier BV
Date: 12-2020
Publisher: Wiley
Date: 31-07-2022
DOI: 10.1111/BCP.14995
Abstract: The purpose of the study was to assess the status of emerging therapeutic drug monitoring (TDM) of anti‐infective agents in Australian hospitals. A nationwide cross‐sectional survey of all Australian hospitals operating in the public and private health sector was conducted between August and September 2019. The survey consisted of questions regarding institutional TDM practice for anti‐infective agents and clinical vignettes specific to β‐lactam antibiotics. Responses were received from 82 unique institutions, representing all Australian states and territories. All 29 (100%) of principal referral (major) hospitals in Australia participated. Five surveys were partially complete. Only 25% (20/80) of hospitals had TDM testing available on‐site for any of the eight emerging TDM candidates considered: β‐lactam antibiotics, anti‐tuberculous agents, flucytosine, fluoroquinolones, ganciclovir, human immunodeficiency virus (HIV) drugs, linezolid and teicoplanin. A considerable time lag was noted between TDM s ling and reporting of results. With respect to β‐lactam antibiotic TDM, variable indications, pharmacodynamic targets and s ling times were identified. The three greatest barriers to local TDM performance were found to be (1) lack of timely assays/results, (2) lack of institutional‐wide expertise and/or training and (3) lack of guidelines to inform ordering of TDM and interpretation of results. The majority of respondents favoured establishing national TDM guidelines and increasing access to dose prediction software, at rates of 89% and 96%, respectively. Translating emerging TDM evidence into daily clinical practice is slow. Concerted efforts are required to address the barriers identified and facilitate the implementation of standardised practice.
Publisher: Springer Science and Business Media LLC
Date: 08-04-2023
DOI: 10.1038/S41467-023-37672-W
Abstract: Shigella sonnei causes shigellosis, a severe gastrointestinal illness that is sexually transmissible among men who have sex with men (MSM). Multidrug resistance in S. sonnei is common including against World Health Organisation recommended treatment options, azithromycin, and ciprofloxacin. Recently, an MSM-associated outbreak of extended-spectrum β-lactamase producing, extensively drug resistant S. sonnei was reported in the United Kingdom. Here, we aimed to identify the genetic basis, evolutionary history, and international dissemination of the outbreak strain. Our genomic epidemiological analyses of 3,304 isolates from the United Kingdom, Australia, Belgium, France, and the United States of America revealed an internationally connected outbreak with a most recent common ancestor in 2018 carrying a low-fitness cost resistance plasmid, previously observed in travel associated sublineages of S. flexneri . Our results highlight the persistent threat of horizontally transmitted antimicrobial resistance and the value of continuing to work towards early and open international sharing of genomic surveillance data.
Publisher: Elsevier BV
Date: 09-2013
Publisher: Georg Thieme Verlag KG
Date: 07-2017
Abstract: Objective: To determine the impact of the introduction of new pre-written orders for antimicrobials in a computerized provider order entry (CPOE) system on 1) accuracy of documented indications for antimicrobials in the CPOE system, 2) appropriateness of antimicrobial prescribing, and 3) compliance with the hospital’s antimicrobial policy. Prescriber opinions of the new decision support were also explored to determine why the redesign was effective or ineffective in altering prescribing practices. Methods: The study comprised two parts: a controlled pre-post study and qualitative interviews. The intervention involved the redesign of pre-written orders for half the antimicrobials so that approved indications were incorporated into pre-written orders. 555 antimicrobials prescribed before (September – October, 2013) and 534 antimicrobials prescribed after (March – April, 2015) the intervention on all general wards of a hospital were audited by study pharmacists. Eleven prescribers participated in semi-structured interviews. Results: Redesign of computerized decision support did not result in more appropriate or compliant antimicrobial prescribing, nor did it improve accuracy of indication documentation in the CPOE system (Intervention antimicrobials: appropriateness 49% vs. 50% compliance 44% vs. 42% accuracy 58% vs. 38% all p .05). Via our interviews with prescribers we identified five main reasons for this, primarily that indications entered into the CPOE system were not monitored or followed-up, and that the antimicrobial approval process did not align well with prescriber workflow. Conclusion: Redesign of pre-written orders to incorporate appropriate indications did not improve antimicrobial prescribing. Workarounds are likely when compliance with hospital policy creates additional work for prescribers or when system usability is poor. Implementation of IT, in the absence of support or follow-up, is unlikely to achieve all anticipated benefits. Citation: Baysari MT, Del Gigante J, Moran M, Sandaradura I, Li L, Richardson KL, Sandhu A, Lehnbom EC, Westbrook JI, Day RO. Redesign of computerized decision support to improve antimicrobial prescribing. Appl Clin Inform 2017 8: 949–963 0.4338/ACI2017042017040069
Publisher: Research Square Platform LLC
Date: 15-09-2022
DOI: 10.21203/RS.3.RS-2057516/V1
Abstract: Shigella sonnei causes shigellosis, a severe gastrointestinal illness that is sexually transmissible among men who have sex with men (MSM). Multidrug resistance in S. sonnei is common and can include resistance to the World Health Organisation recommended treatment options, azithromycin, and ciprofloxacin. Recently, an MSM-associated outbreak of extended-spectrum β-lactamase producing, extensively drug resistant S. sonnei was reported in the United Kingdom. Here, we aimed to identify the genetic basis, natural history, and international dissemination of the outbreak strain. Our genomic epidemiological analyses of 3,304 isolates from the United Kingdom, Australia, Belgium, France, and the United States of America revealed an internationally connected outbreak with a common, low fitness-cost resistance plasmid, previously observed in travel associated sublineages of S. flexneri . Our results highlight the persistent threat of horizontally transmitted antimicrobial resistance and the value of continuing to work towards early and open international sharing of genomic surveillance data.
Publisher: Oxford University Press (OUP)
Date: 11-2018
Abstract: Despite the advantageous spectrum of activity of itraconazole, it is rarely used as a prophylactic agent due to limited bioavailability and intolerance of the conventional formulation. After the development of a novel formulation SUBA-itraconazole® (SUper BioAvailability), we undertook a study to assess therapeutic levels, safety, tolerability, and IFI rates of this novel formulation when compared with the conventional itraconazole liquid in patients undergoing allogeneic hematopoietic stem cell transplantation or in hematological malignancy patients. Following a single-centre, prospective study of SUBA–itraconazole 200 mg BID vs. conventional liquid itraconazole 200 mg BID, the SUBA–itraconazole group was assessed 1-year postallogeneic stem cell transplant for incidence of IFI and survival. A total of 57 patients (29 SUBA–itraconazole and 30 liquid-itraconazole) were assessed. Therapeutic concentrations were achieved significantly more quickly in the SUBA–itraconazole group median of 6 days vs. 14 (P & 0.0001). At day 10, therapeutic concentrations were achieved in 69% of the SUBA–itraconazole group vs. 21% (P & 0.0001). The mean trough serum concentrations at steady state of SUBA–itraconazole were significantly higher, with less interpatient variability (1,577 ng/mL, CV 35%) vs. (1,218 ng/mL, CV 60%) (P & 0.001). There were 2 (7.5%) treatment failures in the SUBA–itraconazole group, both due to cessation of therapy for mucositis, compared with 7 (23.3%) treatment failures in the liquid-itraconazole group, due to subtherapeutic levels (five), mucositis (one), and gastrointestinal intolerance (one) (P = 0.096). There was one confirmed IFI in the SUBA–itraconazole treatment failure group defined by a blood culture that yielded yeast however, this was after the cessation of SUBA–itraconazole for mucositis. No other probable ossible IFIs were observed. After 1 year postallogeneic stem cell transplant in the SUBA–itraconazole group, there were two deaths (10%) due to disease progression and no further IFIs were reported. The use of the SUBA–itraconazole formulation was a safe and effective prophylactic agent. It was associated with more rapid attainment of therapeutic levels with less interpatient variability when compared with conventional liquid itraconazole. J. Lindsay, Mayne Pharma: Consultant, Consulting fee.
Publisher: Oxford University Press (OUP)
Date: 29-09-2022
DOI: 10.1093/JAC/DKAC324
Abstract: Children with cystic fibrosis (CF) pulmonary exacerbations receive IV tobramycin therapy, with dosing guided by either log-linear regression (LLR) or Bayesian forecasting (BF). To compare clinical and performance outcomes for LLR and BF. A quasi-experimental intervention study was conducted at a tertiary children’s hospital. Electronic medical records were extracted (from January 2015 to September 2021) to establish a database consisting of pre-intervention (LLR) and post-intervention (BF) patient admissions and relevant outcomes. All consecutive patients treated with IV tobramycin for CF pulmonary exacerbations guided by either LLR or BF were eligible. A total of 376 hospital admissions (LLR = 248, BF = 128) for CF pulmonary exacerbations were included. Patient demographics were similar between cohorts. There were no significant differences found in overall hospital length of stay, rates of re-admission within 1 month of discharge or change in forced expiratory volume in the first second (Δ FEV1) at the end of tobramycin treatment. Patients treated with LLR on average had twice the number of therapeutic drug monitoring (TDM) blood s les collected during a single hospital admission. The timeframe for blood s ling was more flexible with BF, with TDM s les collected up to 16 h post-tobramycin dose compared with 10 h for LLR. The tobramycin AUC0–24 target of ≥100 mg/L·h was more frequently attained using BF (72% 92/128) compared with LLR (50% 124/248) (P & 0.001). Incidence of acute kidney injury was rare in both groups. LLR and BF result in comparable clinical outcomes. However, BF can significantly reduce the number of blood collections required during each admission, improve dosing accuracy, and provide more reliable target concentration attainment in CF children.
Publisher: Elsevier BV
Date: 12-2020
Publisher: Elsevier BV
Date: 04-2020
DOI: 10.1016/J.JHIN.2020.01.006
Abstract: P2/N95 filtering face piece respirators (FFRs) protect healthcare workers (HCWs) from airborne infections. This study assessed the impact of facial hair on quantitative respirator fit in 105 male HCWs, of whom 38 were clean shaven, and assessed the prevalence of male facial hair at the study facility. Only 34 (32%) male HCWs overall achieved an adequate FFR fit, including 47% of clean-shaven men. No full-bearded HCWs achieved a fit. Adequate respirator fit decreased significantly with increasing facial hair (P<0.01 for trend). Facial hair was present on 49% of male employees. This study supports quantitative fit testing prior to P2/N95 respirator use.
Publisher: Oxford University Press (OUP)
Date: 27-08-2020
DOI: 10.1093/OFID/OFAA387
Abstract: Testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific antibodies has become an important tool, complementing nucleic acid tests (NATs) for diagnosis and for determining the prevalence of coronavirus disease 2019 (COVID-19) in population serosurveys. The magnitude and persistence of antibody responses are critical for assessing the duration of immunity. A SARS-CoV-2-specific immunofluorescent antibody (IFA) assay for immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM) was developed and prospectively evaluated by comparison to the reference standard of NAT on respiratory tract s les from in iduals with suspected COVID-19. Neutralizing antibody responses were measured in a subset of s les using a standard microneutralization assay. A total of 2753 in iduals were eligible for the study (126 NAT-positive prevalence, 4.6%). The median “window period” from illness onset to appearance of antibodies (range) was 10.2 (5.8–14.4) days. The sensitivity and specificity of either SARS-CoV-2 IgG, IgA, or IgM when collected ≥14 days after symptom onset were 91.3% (95% CI, 84.9%–95.6%) and 98.9% (95% CI, 98.4%–99.3%), respectively. The negative predictive value was 99.6% (95% CI, 99.3%–99.8%). The positive predictive value of detecting any antibody class was 79.9% (95% CI, 73.3%–85.1%) this increased to 96.8% (95% CI, 90.7%–99.0%) for the combination of IgG and IgA. Measurement of SARS-CoV-2-specific antibody by IFA is an accurate method to diagnose COVID-19. Serological testing should be incorporated into diagnostic algorithms for SARS-CoV-2 infection to identify additional cases where NAT was not performed and resolve cases where false-negative and false-positive NATs are suspected. The majority of in iduals develop robust antibody responses following infection, but the duration of these responses and implications for immunity remain to be established.
Publisher: American Society for Microbiology
Date: 18-05-2021
DOI: 10.1128/AAC.00465-21
Publisher: Elsevier BV
Date: 05-2023
Publisher: Georg Thieme Verlag KG
Date: 2013
DOI: 10.4338/ACI-2013-08-RA-0063
Abstract: Background: There is now little doubt that improving antimicrobial use is necessary for the containment of resistance. Objective: To determine whether providing in idualised feedback to doctors about their recent compliance with the hospital’s antibiotic policy improves compliance with the policy. Methods: This study was conducted at a teaching hospital in Sydney, Australia. Computerised alerts integrated into the electronic prescribing system (ePS) inform prescribers of the local antibiotic policy. We utilised prescribing data extracted from the ePS for ‘audit and feedback’. Thirty-six prescribers were sent feedback letters via email. We also interviewed doctors who had received letters to explore their views of the feedback and the policy in general. Results: There was no significant change in compliance with the policy following implementation of the feedback intervention (0% compliant vs 11.9% p = 0.07). Several problems with the policy and the approval process were identified by researchers during auditing and by prescribers during interviews. Some problems identified made it difficult to accurately assess compliance and for doctors to comply with the policy. Conclusions: Our intervention did not result in improved compliance with the antibiotic policy but revealed practical problems with the policy and approval process that had not been identified prior to the trial. Greater support for the policy by senior doctors and the assignment of more clearly defined roles and responsibilities associated with antibiotic use and approval may result in improved compliance. Harnessing the full potential of technology would streamline the antimicrobial approval process and allow more efficient and reliable monitoring of antibiotic use and compliance. Many of the problems we identified are generic issues of importance to all organisations seeking to integrate antimicrobial stewardship into ePS. Citation: Baysari MT, Oliver K, Egan B, Li L, Richardson K, Sandaradura I, Westbrook J I, Day RO. Audit and feedback of antibiotic use: Utilising electronic prescription data. Appl Clin Inf 2013 4: 583–595 0.4338/ACI-2013-08-RA-0063
Publisher: Informa UK Limited
Date: 12-2019
DOI: 10.2147/IJN.S228919
Publisher: Springer Science and Business Media LLC
Date: 13-11-2018
DOI: 10.1007/S40262-017-0610-9
Abstract: Bayesian forecasting (BF) methods for tobramycin dose in idualisation has not seen widespread clinical adoption, despite being endorsed by clinical practice guidelines. Several freeware and commercial programmes using BF methods are available to support personalised dosing. This study evaluated exposure estimates, dose recommendations, and predictive performance compared with current clinical practice. Data from 105 patients (50 adults and 55 children) with cystic fibrosis who received intravenous tobramycin treatment and had paired concentration-time measurements were analysed using (1) log-linear regression analysis, and (2) three BF programmes: TDMx, InsightRX, and DoseMe. Exposure estimates and dose recommendations were compared using the Wilcoxon signed-rank test and Bland-Altman analysis. Predictive performance of BF programmes was compared based on bias and imprecision. Median estimated tobramycin exposure with current clinical practice was significantly lower (87.8 vs. 92.5, 94.0 and 90.3 mg h l On average, the predictions made by the BF programmes were similar, however substantial in idual differences were observed for some patients. This suggests the need for detailed investigations of true tobramycin exposure.
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1016/J.IJANTIMICAG.2019.05.013
Abstract: Urinary tract infections caused by multidrug-resistant Enterobacteriaceae are a growing burden worldwide. Recent studies of urinary pharmacokinetics described high piperacillin/tazobactam (TZP) concentrations in urine, but it is unknown whether this results in treatment efficacy. This study investigated the pharmacodynamics of TZP in a static in vitro model for Enterobacteriaceae to determine the concentration-effect relationship and ultimately the required free (unbound) time above the minimum inhibitory concentration (fT
Publisher: Wiley
Date: 06-08-2019
DOI: 10.1111/BCP.14066
Publisher: Cambridge University Press (CUP)
Date: 26-05-2016
DOI: 10.1017/S0031182016000652
Abstract: Angiostrongylus cantonensis is a metastrongyloid nematode found widely in the Asia-Pacific region, and the aetiological agent of angiostrongyliasis a disease characterized by eosinophilic meningitis. Rattus rats are definitive hosts of A. cantonensis , while intermediate hosts include terrestrial and aquatic molluscs. Humans are dead-end hosts that usually become infected upon ingestion of infected molluscs. A presumptive diagnosis is often made based on clinical features, a history of mollusc consumption, eosinophilic pleocytosis in cerebral spinal fluid, and advanced imaging such as computed tomography. Serological tests are available for angiostrongyliasis, though many tests are still under development. While there is no treatment consensus, therapy often includes a combination of anthelmintics and corticosteroids. Angiostrongyliasis is relatively rare, but is often associated with morbidity and sometimes mortality. Recent reports suggest the parasites’ range is increasing, leading to fatalities in regions previously considered Angiostrongylus -free, and sometimes, delayed diagnosis in newly invaded regions. Increased awareness of angiostrongyliasis would facilitate rapid diagnosis and improved clinical outcomes. This paper summarizes knowledge on the parasites’ life cycle, clinical aspects and epidemiology. The molecular biology of Angiostrongylus spp. is also discussed. Attention is paid to the significance of angiostrongyliasis in Australia, given the recent severe cases reported from the Sydney region.
Publisher: American Society for Microbiology
Date: 17-02-2021
DOI: 10.1128/AAC.02019-20
Abstract: Fluconazole has been associated with higher mortality compared with the echinocandins in patients treated for invasive candida infections. Underexposure from current fluconazole dosing regimens may contribute to these worse outcomes, so alternative dosing strategies require study.
Publisher: Public Library of Science (PLoS)
Date: 03-03-2015
Publisher: Oxford University Press (OUP)
Date: 11-09-2017
DOI: 10.1093/JAC/DKX295
Abstract: To assess therapeutic levels, safety and tolerability of a novel formulation SUBA-itraconazole (where SUBA stands for SUper BioAvailability) when compared with conventional itraconazole liquid when used as antifungal prophylaxis in patients undergoing allogeneic HSCT or in haematological malignancy patients with an intermediate/high risk of invasive fungal infection (IFI). This was a single-institution, prospective cohort study using a historical control group as the comparator. A total of 57 patients were assessed: 27 in the SUBA-itraconazole cohort and 30 in the liquid itraconazole cohort. Therapeutic concentrations were achieved significantly more quickly in the SUBA-itraconazole group: median of 6 (95% CI 5-11) days versus 14 (95% CI 12-21) days in the liquid itraconazole group (P < 0.0001). At day 10, therapeutic concentrations were achieved in 69% (95% CI 44%-81%) of the SUBA-itraconazole group versus 21% (95% CI 7%-33%) of the liquid itraconazole group (P < 0.0001). The mean trough serum concentrations at steady-state of SUBA-itraconazole were significantly higher, with less interpatient variability [1577 ng/mL, coefficient of variation (CV) 35%] versus liquid itraconazole (1218 ng/mL, CV 60%) (P < 0.001). There were two (7.4%) treatment failures in the SUBA-itraconazole group, both due to cessation of therapy for mucositis, compared with seven (23.3%) treatment failures in the liquid itraconazole group, due to subtherapeutic levels (five), mucositis (one) and gastrointestinal intolerance (one) (P = 0.096). The use of the SUBA-itraconazole formulation was associated with more rapid attainment of therapeutic levels with less interpatient variability compared with conventional liquid itraconazole when used as IFI prophylaxis in allogeneic HSCT or intermediate-/high-IFI risk haematological malignancy patients.
Publisher: Elsevier BV
Date: 02-2019
Publisher: Wiley
Date: 02-2019
DOI: 10.1111/JPC.14333
Publisher: American Society for Microbiology
Date: 05-2017
DOI: 10.1128/AAC.02535-16
Abstract: Unlike vancomycin trough concentrations, data on the utility of vancomycin pharmacokinetic (PK) parameters, namely, the area under the concentration-time curve from 0 to 24 h (AUC 0–24 ), in predicting acute kidney injury (AKI) are limited. Our aim was to investigate this relationship in patients receiving vancomycin therapy for methicillin-resistant Staphylococcus aureus bacteremia (MRSA-B). A single-center retrospective observational cohort study involving 127 consecutive MRSA-B patients was conducted to examine the incidence of AKI (defined as serum creatinine of ≥0.5 mg/liter and a 50% increase from baseline) and vancomycin exposure parameters associated with nephrotoxicity. Bayesian estimation was used to predict in idual vancomycin AUC 0–24 . All patients received vancomycin monotherapy for a minimum of 14 days following the diagnosis of MRSA-B. AKI was observed in 15.7% of patients (20/127). Clinical characteristics were similar between patients with and without AKI. At steady state, higher vancomycin trough concentrations were associated with AKI (17.2 mg/liter versus 13.1 mg/liter P = 0.003). A vancomycin AUC 0–24 threshold for AKI of mg · h/liter was detected by classification and regression tree (CART) analysis patients with exposures above this threshold were significantly more likely to experience AKI than patients with lower vancomycin exposures (40% [8/20] versus 11.2% [12/107] P = 0.002). This parameter remained an independent predictor of AKI on multivariate logistic regression (odds ratio [OR], 5.07 95% confidence interval [CI], 1.57 to 16.29 P = 0.006) and was a better predictor of nephrotoxicity than vancomycin trough concentrations. Overall, AKI is associated with higher vancomycin exposure as measured by AUC 0–24 . These results suggest that in idualized patient dosing may be possible with dose modifications directed toward established pharmacodynamic targets while balancing AKI risks.
Publisher: Oxford University Press (OUP)
Date: 24-01-2023
DOI: 10.1093/JAC/DKAD005
Abstract: Beta-lactam antibiotics are the mainstay of therapy for most bacterial causes of infective endocarditis (IE). Traditionally considered as agents with a broad therapeutic index, there is increasing recognition that standard doses may be subtherapeutic or toxic in critically ill patients. Optimizing therapy for efficacy requires a defined pharmacokinetic (PK) harmacodynamic (PD) target associated with clinical and microbiological cure. To elucidate the factors that influence beta-lactam PK and PD variability in IE and to examine optimal PK/PD target parameters for therapy. The review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Clinical and laboratory in vivo animal or human studies examining PK and/or PD of beta-lactam antibiotics in IE were eligible. Ovid MEDLINE, Embase and Cochrane Central Registry were searched using defined terms. The Office of Health Assessment and Translation (OHAT) tool was used for assessing risk of bias. From 2677 abstracts, 62 articles were selected for review and synthesis, comprising: 45 animal studies investigating the broad categories of beta-lactam diffusion into vegetations, PK/PD determinants of outcome, mode of antibiotic delivery and synergistic impact of agents and 17 human studies totalling 347 participants. Findings supported the importance of time-dependent killing for beta-lactams but heterogeneous data limited the determination of an optimal PK/PD target for IE treatment. Beta-lactam PK and PD in endocarditis are variable and specific to the particular antibiotic-organism combination. Time-dependent killing is important, consistent with non-endocarditis studies, but there is little agreement on optimal drug exposure. Clinical studies examining PK/PD targets in endocarditis are required to further inform drug selection and dosing.
No related grants have been discovered for Indy Sandaradura.