ORCID Profile
0000-0003-1232-5884
Current Organisations
Epworth Freemasons
,
Austin Health
,
Peter MacCallum Cancer Centre
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Publisher: Elsevier BV
Date: 03-2021
Publisher: Springer Science and Business Media LLC
Date: 10-06-2019
DOI: 10.1007/S11908-019-0679-4
Abstract: Carbapenem-resistant Enterobacteriaceae (CRE) have emerged as a worldwide problem. Given their degree of immunosuppression and the level of contact with the healthcare system, solid organ transplant (SOT) recipients are at a disproportionately higher risk of acquisition, colonization, and infection with CRE, and outcomes from infection tend to be worse compared to non-transplant patients. Therapeutic options are limited for CRE infections although several newer agents have recently been approved for use. How well these agents perform in the setting of immunosuppression and SOT is unclear. We sought to review the epidemiology of CRE in SOT and the management principles. CRE infections are becoming an increasing problem in SOT, and donor-derived infections present a challenge in the peri-transplant period. Newer treatments for CRE are emerging that are less toxic and potentially more effective than prior CRE-active agents, but supportive clinical data are limited. Newer beta-lactamase inhibitors have good activity against KPC carbapenemases, but they lack activity against metallo-beta-lactamases (e.g., NDM). Promising data is emerging with newer agents that have activity against most carbapenemases, but, again, clinical data is needed. Combination therapy in addition to optimal pharmacokinetic and pharmacodynamics may go some way to improve outcomes against these difficult-to-treat organisms. Other novel therapies that prevent the emergence of resistance (oral beta-lactamase inhibitors) and eradication of resistant Gram-negative colonization (fecal microbiota transplant) may eventually become part of a bundle approach to reduce CRE infections in the future. As in non-transplant patients, CRE infections in the transplant setting are challenging to treat and prevent. Infection prevention and control remains crucial to prevent widespread dissemination, and unique challenges exist with donor-derived CRE and how best to manage recipients in the peri-transplant period. Newer treatments are now in early-phase clinical studies, and in vitro activity data are supportive for several agents providing hope for improved outcomes with these typically difficult-to-treat and highly morbid infections in transplant recipients.
Publisher: Elsevier BV
Date: 07-2018
DOI: 10.1016/J.JHIN.2018.02.013
Abstract: Few studies have used molecular epidemiological methods to study transmission links to clinical isolates in intensive care units. Ninety-four multidrug-resistant organisms (MDROs) cultured from routine specimens from intensive care unit (ICU) patients over 13 weeks were stored (11 meticillin-resistant Staphylococcus aureus (MRSA), two vancomycin-resistant enterococci and 81 Gram-negative bacteria). Medical staff personal mobile phones, departmental phones, and ICU keyboards were swabbed and cultured for MDROs MRSA was isolated from two phones. Environmental and patient isolates of the same genus were selected for whole genome sequencing. On whole genome sequencing, the mobile phone isolates had a pairwise single nucleotide polymorphism (SNP) distance of 183. However, >15,000 core genome SNPs separated the mobile phone and clinical isolates. In a low-endemic setting, mobile phones and keyboards appear unlikely to contribute to hospital-acquired MDROs.
Publisher: Elsevier BV
Date: 11-2020
Publisher: Elsevier BV
Date: 06-2016
Publisher: Elsevier BV
Date: 04-2021
Publisher: Wiley
Date: 10-2017
DOI: 10.1111/IMJ.13562
Publisher: Wiley
Date: 19-02-2018
DOI: 10.1111/TID.12838
Abstract: Mycobacterium abscessus infection following lung transplantation has historically been associated with poor outcomes. We report a case of bilateral lung retransplantation complicated by obstruction of the right pulmonary artery secondary to M. abscessus mycotic aneurysm. Aggressive surgical management, including reconstruction of the right pulmonary artery, was undertaken with prolonged antimicrobial therapy. Thirty-six months later, antibiotics have been discontinued and the patient has stable soft tissue chest wall disease with good graft function. Mortality and morbidity associated with M. abscessus infection is considerable but this case illustrates that with aggressive early management, outcomes may be favorable.
Publisher: Cold Spring Harbor Laboratory
Date: 15-01-2021
DOI: 10.1101/2021.01.14.21249853
Abstract: In our study, procalcitonin was associated with both antibiotic use and duration in patients with COVID-19, as well as established biochemical markers of COVID-19 disease severity and oxygen requirement, suggesting a potential role for procalcitonin in COVID-19 antimicrobial stewardship.
Publisher: Oxford University Press (OUP)
Date: 17-11-2018
DOI: 10.1093/OFID/OFY306
Abstract: Antibiotic allergies are reported by up to 1 in 4 cancer patients, almost 50% of which are considered low risk and precede the cancer diagnosis. We demonstrate the successful and safe implementation of a pilot oral penicillin challenge program for cancer patients with low-risk penicillin allergies, increasing the use of penicillin and narrow-spectrum beta-lactams post-testing.
Publisher: Therapeutic Guidelines Limited
Date: 02-2021
Publisher: Wiley
Date: 31-08-2018
DOI: 10.1111/TID.12976
Abstract: Cryptococcosis is a common invasive fungal infection (IFI) in solid organ transplant (SOT) recipients. Little is known about cryptococcosis in lung transplant (LTx) recipients despite having one of the highest risks of infection. The aim of this study was to describe demographic and clinical features of cryptococcal infection in LTx recipients. We performed a retrospective, observational study of cryptococcal infection in LTx recipients at The Alfred Hospital in Melbourne, Australia, from 2012 to 2017. A total of 11 cases were identified. Seven patients (64%) were male and the median age was 54.7 years (range 34-69 years). Diagnosis occurred at a median of 233 days (range 1-3650 days) post-transplant. Nine patients (82%) had isolated pulmonary infection of whom 7 (78%) were asymptomatic. All were treated with oral antifungal therapy and 1 required surgical resection of infected lung. Two patients (18%) had disseminated infection 1 with pulmonary and central nervous system (CNS) infection and 1 with isolated CNS infection. Both patients presented with headache and brain imaging demonstrated cerebral edema, myelinosis, and leptomeningeal enhancement. One of these patients died. This study highlights the fact that cryptococcal infection should remain a consideration in asymptomatic LTx recipients, especially in the presence of non-specific nodules on chest imaging, and that the presence of headache in these patients requires urgent investigation for CNS infection.
Publisher: Wiley
Date: 02-2018
DOI: 10.1111/IMJ.13703
Abstract: Given the long term sequelae of untreated neurosyphilis and insensitive tests to detect treponemes in the cerebrospinal fluid, questions regarding the utility of a lumbar puncture and cerebrospinal fluid analysis either to confirm or exclude neurosyphilis are raised.
Publisher: Elsevier BV
Date: 02-2019
Publisher: Medknow
Date: 2019
Publisher: Massachusetts Medical Society
Date: 08-10-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 22-09-2020
Publisher: Springer Science and Business Media LLC
Date: 16-04-2021
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: Wiley
Date: 07-2020
DOI: 10.1111/IMJ.14888
Publisher: Springer Science and Business Media LLC
Date: 12-11-2020
DOI: 10.1007/S00520-019-05093-5
Abstract: CRS-HIPEC is associated with improved cancer survival but an increased risk of infection. Consecutive patients undergoing CRS-HIPEC between January 2016 and May 2018 were retrospectively reviewed. Malignancy type, comorbidities, perioperative risk factors and infectious complications were captured, using standardised definitions. Association between risk factors and infection outcomes was evaluated by logistic regression modelling. One-hundred patients underwent CRS-HIPEC, predominantly for colorectal cancer and pseudomyxoma peritonei. Overall, 43 (43.0%) experienced an infectious complication, including infections at surgical site (27), respiratory tract (9), urinary tract (11), Clostridium difficile (2) and post-operative sepsis (15). In most, infection onset was within 7 days post-operatively. Median length of hospitalisation was 19 days for patients with infection, compared to 8 days for those without (p = 0.000). There were no deaths at 60 days. Of variables potentially associated with surgical site infection, small bowel resection (OR 4.01, 95% confidence interval [CI] 1.53-10.83 p = 0.005) and number of resected viscera (OR 1.41, 95% CI 1.00-1.98 p = 0.048) were significantly associated with infection. We demonstrate a significant burden of early infective complications in patients undergoing CRS-HIPEC. Higher-risk subgroups, including those with small bowel resection and increased number of resected viscera, may benefit from enhanced monitoring.
Publisher: Elsevier BV
Date: 05-2019
DOI: 10.1016/J.IJID.2019.03.003
Abstract: The confirmation or analysis and exclusion of a diagnosis of neurosyphilis has long presented a challenge for infectious diseases clinicians. The authors reviewed the concordance between cerebrospinal fluid (CSF) analysis and the subsequent antibiotic strategy for patients undergoing evaluation of a diagnosis of neurosyphilis. All patients with positive serum syphilis serology referred for CSF analysis between January 2009 and May 2016 were included. Indications for CSF analysis were determined by review of the hospital electronic medical records. CSF parameters were determined from the hospital pathology database. Cases were defined as either 'confirmed', 'supportive' of, or 'not supportive' of a diagnosis of neurosyphilis based on existing definitions. Subsequent therapy was defined as for neurosyphilis, late latent primary syphilis or no therapy based on existing guidelines. Of 131 patients reviewed, 95.4% were male and HIV co-infected (74%). A confirmed diagnosis of neurosyphilis was met by fourteen patients (10.7%). All but two of these were treated with a neurosyphilis-directed regimen. Of the 58 patients treated with neurosyphilis antibiotics, 17.2% had no CSF findings suggestive of the diagnosis. Seventy-three patients were not treated for neurosyphilis however 35 of these met the CSF criteria for a diagnosis supportive of neurosyphilis. The results of routine CSF analysis in patients with a possible diagnosis of neurosyphilis are inconsistently applied in the clinical setting, calling into question the value of routine CSF. Empirical neurosyphilis treatment should be considered up front in patients with high pre-test probability of the diagnosis.
Publisher: Mary Ann Liebert Inc
Date: 12-2017
Publisher: Elsevier BV
Date: 03-2019
Publisher: Elsevier BV
Date: 09-2020
Publisher: Cambridge University Press (CUP)
Date: 25-01-2022
DOI: 10.1017/ICE.2021.28
Publisher: Elsevier BV
Date: 04-2020
Publisher: Springer Science and Business Media LLC
Date: 24-05-2021
Publisher: Oxford University Press (OUP)
Date: 05-07-2017
DOI: 10.1093/CID/CIX601
Abstract: Invasive and disseminated Mycoplasma hominis infections are well recognized but uncommon complications in solid organ transplant recipients. In a single center, a cluster of M. hominis infections were identified in lung transplant recipients from the same thoracic intensive care unit (ICU). We sought to determine the source(s) of these infections. Medical records of the donor and infected transplant recipients were reviewed for clinical characteristics. Clinical specimens underwent routine processing with subculture on Mycoplasma-specific Hayflick agar. Mycoplasma hominis identification was confirmed using sequencing of the 16S ribosomal RNA gene. Mycoplasma hominis isolates were subjected to whole-genome sequencing on the Illumina NextSeq platform. Three lung transplant recipients presented with invasive M. hominis infections at multiple sites characterized by purulent infections without organisms detected by Gram staining. Each patient had a separate donor however, pretransplant bronchoalveolar lavage fluid was only available from the donor for patient 1, which subsequently grew M. hominis. Phylo- and pangenomic analyses indicated that the isolates from the donor and the corresponding recipient (patient 1) were closely related and formed a distinct single clade. In contrast, isolates from patients 2 and 3 were unrelated and ergent from one another. Mycoplasma hominis should be considered a cause of donor-derived infection. Genomic data suggest donor-to-recipient transmission of M. hominis. Additional patients co-located in the ICU were found to have genetically unrelated M. hominis isolates, excluding patient-to-patient transmission.
Publisher: Elsevier BV
Date: 07-2017
Publisher: Elsevier BV
Date: 2020
DOI: 10.2139/SSRN.3751796
Publisher: Informa UK Limited
Date: 02-06-2017
Publisher: Public Library of Science (PLoS)
Date: 09-12-2020
DOI: 10.1371/JOURNAL.PONE.0243414
Abstract: We report on the key clinical predictors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and present a clinical decision rule that can risk stratify patients for COVID-19. A prospective cohort of patients assessed for COVID-19 at a screening clinic in Melbourne, Australia. The primary outcome was a positive COVID-19 test from nasopharyngeal swab. A backwards stepwise logistic regression was used to derive a model of clinical variables predictive of a positive COVID-19 test. Internal validation of the final model was performed using bootstrapped s les and the model scoring derived from the coefficients, with modelling performed for increasing prevalence. Of 4226 patients with suspected COVID-19 who were assessed, 2976 patients underwent SARS-CoV-2 testing (n = 108 SARS-CoV-2 positive) and were used to determine factors associated with a positive COVID-19 test. The 7 features associated with a positive COVID-19 test on multivariable analysis were: C OVID-19 patient exposure or international travel, M yalgia/malaise, A nosmia or ageusia, T emperature, C oryza/sore throat, H ypoxia–oxygen saturation 97%, 65 years or older—summarized in the mnemonic C OVID- MATCH65 . Internal validation showed an AUC of 0.836. A cut-off of ≥ 1.5 points was associated with a 92.6% sensitivity and 99.5% negative predictive value (NPV) for COVID-19. From the largest prospective outpatient cohort of suspected COVID-19 we define the clinical factors predictive of a positive SARS-CoV-2 test. The subsequent clinical decision rule, COVID-MATCH65, has a high sensitivity and NPV for SARS-CoV-2 and can be employed in the pandemic, adjusted for disease prevalence, to aid COVID-19 risk-assessment and vital testing resource allocation.
Publisher: Elsevier BV
Date: 2021
DOI: 10.2139/SSRN.3750715
Publisher: Cold Spring Harbor Laboratory
Date: 02-07-2020
DOI: 10.1101/2020.06.30.20143818
Abstract: Due to the ongoing COVID-19 pandemic and increased pressure on testing resources, understanding the clinical and epidemiological features closely associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is vital at point of care to enable risk stratification. We demonstrate that an internally derived and validated clinical decision rule, COVID-MATCH65, has a high sensitivity (92.6%) and NPV (99.5%) for SARS-CoV-2 and could be used to aid COVID-19 risk-assessment and resource allocation for SARS-CoV-2 diagnostics.
Publisher: Wiley
Date: 11-01-2019
DOI: 10.1111/BCP.13830
Publisher: Frontiers Media SA
Date: 17-03-2021
DOI: 10.3389/FIMMU.2021.646095
Abstract: The association of pro-inflammatory markers such as interleukin-6 (IL-6) and other biomarkers with severe coronavirus disease 2019 (COVID-19) is of increasing interest, however their kinetics, response to current COVID-related treatments, association with disease severity and comparison with other disease states associated with potential cytokine storm (CS) such as Staphylococcus aureus bacteraemia (SAB) are ill-defined. A cohort of 55 hospitalized SARS-CoV-2 positive patients was prospectively recruited – blood s ling was performed at baseline, post-treatment and hospital discharge. Serum IL-6, C-reactive protein (CRP) and other laboratory investigations were compared between treatment groups and across timepoints. Acute serum IL-6 and CRP levels were then compared to those with suspected COVID-19 (SCOVID) and age and sex matched patients with SAB and patients hospitalized for any non-infectious condition (NIC). IL-6 was elevated at admission in the SARS-CoV-2 cohort but at lower levels compared to matched SAB patients. Median (IQR) IL-6 at admission was 73.89 pg/mL (30.9, 126.39) in SARS-CoV-2 compared to 92.76 pg/mL (21.75, 246.55) in SAB (p=0.017) 12.50 pg/mL (3.06, 35.77) in patients with NIC and 95.51 pg/mL (52.17, 756.67) in SCOVID. Median IL-6 and CRP levels decreased between admission and discharge timepoints. This reduction was lified in patients treated with remdesivir and/or dexamethasone. CRP and bedside vital signs were the strongest predictors of COVID-19 severity. Knowledge of the kinetics of IL-6 did not offer enhanced predictive value for disease severity in COVID-19 over common investigations such as CRP and vital signs.
Publisher: Elsevier BV
Date: 08-2017
Publisher: Therapeutic Guidelines Limited
Date: 17-06-2020
Location: United Kingdom of Great Britain and Northern Ireland
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