Infectious Diseases - Research Publications
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ItemDiagnosis, management and prevention of Candida auris in hospitals: position statement of the Australasian Society for Infectious Diseases(WILEY, 2019-10)Candida auris is an emerging drug-resistant yeast responsible for hospital outbreaks. This statement reviews the evidence regarding diagnosis, treatment and prevention of this organism and provides consensus recommendations for clinicians and microbiologists in Australia and New Zealand. C. auris has been isolated in over 30 countries (including Australia). Bloodstream infections are the most frequently reported infections. Infections have crude mortality of 30-60%. Acquisition is generally healthcare-associated and risks include underlying chronic disease, immunocompromise and presence of indwelling medical devices. C. auris may be misidentified by conventional phenotypic methods. Matrix-assisted laser desorption ionisation time-of-flight mass spectrometry or sequencing of the internal transcribed spacer regions and/or the D1/D2 regions of the 28S ribosomal DNA are therefore required for definitive laboratory identification. Antifungal drug resistance, particularly to fluconazole, is common, with variable resistance to amphotericin B and echinocandins. Echinocandins are currently recommended as first-line therapy for infection in adults and children ≥2 months of age. For neonates and infants <2 months of age, amphotericin B deoxycholate is recommended. Healthcare facilities with C. auris should implement a multimodal control response. Colonised or infected patients should be isolated in single rooms with Standard and Contact Precautions. Close contacts, patients transferred from facilities with endemic C. auris or admitted following stay in overseas healthcare institutions should be pre-emptively isolated and screened for colonisation. Composite swabs of the axilla and groin should be collected. Routine screening of healthcare workers and the environment is not recommended. Detergents and sporicidal disinfectants should be used for environmental decontamination.
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ItemHepatitis B management during immunosuppression for haematological and solid organ malignancies: an Australian consensus statement(WILEY, 2019-06)INTRODUCTION: Individuals with chronic hepatitis B virus (HBV) infection or past exposure to HBV infection have a substantial risk of reactivation during immunosuppressive cancer therapy. HBV reactivation can lead to liver failure, cancer treatment interruption or death. Clinical concordance with screening and treatment guidelines is inconsistent in practice, and existing international guidelines are not specific to the Australian context. We developed an Australian consensus statement with infectious diseases, hepatology, haematology and oncology specialists to inform hepatitis B screening and antiviral management for immunocompromised patients with haematological and solid organ malignancies in Australia. MAIN RECOMMENDATIONS: Recommendations address four key areas of HBV infection management for immunocompromised patients with haematological and solid organ malignancies: who to test for HBV infection, when to start antiviral agents, when to stop antiviral agents, and how to monitor patients during cancer therapy. We recommend testing all patients undergoing cancer treatment for hepatitis B (including HBV surface antigen [HBsAg], HBV core antibody [anti-HBc], and HBV surface antibody) before cancer treatment. Individuals with chronic HBV infection (HBsAg positive) or past exposure (HBsAg negative and anti-HBc positive) receiving higher risk chemotherapy require antiviral prophylaxis using entecavir or tenofovir. CHANGES IN MANAGEMENT AS A RESULT OF THIS STATEMENT: This consensus statement will simplify the approach to testing and prophylaxis for HBV infection during cancer therapy, and harmonise approaches to discontinuing and monitoring individuals which have been highly variable in practice. We advocate for broader Medicare Benefits Schedule and Pharmaceutical Benefits Scheme access to HBV testing and treatment for patients undergoing cancer therapy.
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ItemAccess, knowledge and experience with fluorodeoxyglucose positron emission tomography/computed tomography in infection management: a survey of Australia and New Zealand infectious diseases physicians and microbiologists(WILEY, 2019-05)BACKGROUND: Despite fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) being funded only for staging and restaging of some malignancies in Australia, there is evidence of benefit of FDG-PET/CT for infection indications such as pyrexia of unknown origin (PUO), prolonged neutropenic fever (NF) and prosthetic device infection. AIM: To evaluate the current knowledge, utilisation of and gaps in access to FDG-PET/CT for infectious indications by Australasian infectious diseases (ID) physicians and microbiologists. METHODS: An online survey was administered to ID and microbiology doctors practising in adult medicine in Australia and New Zealand through two established email networks. Using targeted questions and case-based examples, multiple themes were explored, including access to FDG-PET/CT, use and perceived benefit of FDG-PET/CT in diagnosis and monitoring of non-malignant conditions such as NF and PUO, and barriers to clinical use of FDG-PET/CT. RESULTS: A response was received from 120 participants across all states and territories. Onsite and offsite FDG-PET/CT access was 63% and 31% respectively. Eighty-six percent reported using FDG-PET/CT for one or more infection indications and all had found it clinically useful, with common indications being PUO, prosthetic device infections and use in the immunocompromised host for prolonged NF and invasive fungal infection. Thirty-eight percent reported barriers in accessing FDG-PET/CT for infection indications and 76% would utilise FDG-PET/CT more frequently if funding existed for infection indications. CONCLUSION: Access to FDG-PET/CT in Australia and New Zealand is modest and is limited by lack of reimbursement for infection indications. There is discrepancy between recognised ID indications for FDG-PET/CT and funded indications.
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ItemImpact of a hospital-wide sepsis pathway on improved quality of care and clinical outcomes in surgical patients at a comprehensive cancer centre(WILEY, 2019-05)PURPOSE: Sepsis is a significant complication following cancer surgery. Although standardised care bundles improve sepsis outcomes in other populations, the benefits in cancer patients are unclear. The objectives of this study were to describe the epidemiology of sepsis in cancer patients post-surgery, and to evaluate the impact of a clinical sepsis pathway on management and clinical outcomes. METHODS: A standardised hospital-wide sepsis pathway was developed in 2013, and all cases of sepsis at the Peter MacCallum Cancer Centre in 2014 were retrospectively evaluated. Inclusion criteria were sepsis onset during the 100-day period following a surgical procedure for cancer diagnosis. Patients were identified using ICD-10-AM sepsis discharge codes, audit documentation and the hospital's antimicrobial approval system. Sepsis episodes were classified as managed on- or off-pathway. RESULTS: A total of 119 sepsis episodes were identified. Of these, 71 (59.7%) were managed on the sepsis pathway. Episodes managed on-pathway resulted more frequently in administration of appropriate antibiotics compared to those off-pathway (94.4% vs. 66.7%, p < 0.001), and had shorter time to first-dose antibiotics (median 85 vs. 315 min, p < 0.001). Pathway utilisation was associated with significant reductions in need for inotropes (7% vs. 13%, p = 0.023), ventilation (3% vs. 10%, p = 0.006) and length of hospitalisation (median 15 vs. 30 days, p = 0.008). The most frequent source of infection was organ-space surgical site infection (24.4% of instances). CONCLUSIONS: A dedicated hospital-wide sepsis pathway had significant impact on the quality of care and clinical outcomes of sepsis in cancer surgery patients. Cost-benefit analysis of sepsis pathways for cancer patients is required.
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ItemNo Preview AvailableViral Respiratory Tract Infections in Allogeneic Hematopoietic Stem Cell Transplantation Recipients in the Era of Molecular Testing(ELSEVIER SCIENCE INC, 2018-07)Viral respiratory tract infection (vRTI) is a significant cause of morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study aimed to assess the epidemiologic characteristics, risk factors, and outcomes of vRTI occurring in the period from conditioning to 100 days after allo-HSCT in the era of molecular testing. This study was a retrospective record review of patients who underwent allo-HSCT at Royal Melbourne Hospital between January 2010 and December 2015. Symptomatic patients were tested using respiratory multiplex polymerase chain reaction (PCR). Logistic regression and Kaplan-Meier analysis were used to identify risk factors for vRTI and the risk of death or intensive care unit (ICU) admission, respectively. A total of 382 patients were reviewed, and 65 episodes of vRTI were identified in 56 patients (14.7%). Rhinovirus accounted for the majority of infections (69.2%). The majority of episodes presented initially with upper respiratory tract infection (58.5%), with 28.9% of them progressing to lower respiratory tract infection. Eleven episodes (16.9%) were associated with ICU admission. There were no deaths directly due to vRTI. Previous autologous HSCT was associated with an increased risk of vRTI (odds ratio, 2.1; 95% confidence interval, 1.0 to 4.1). The risks of death (P = .47) or ICU admission (P = .65) were not significantly different by vRTI status. vRTI is common in the first 100 days after allo-HSCT and is associated with ICU admission.
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ItemPredicting Infectious ComplicatioNs in Children with Cancer: an external validation study(NATURE PUBLISHING GROUP, 2017-07-11)BACKGROUND: The aim of this study was to validate the 'Predicting Infectious ComplicatioNs in Children with Cancer' (PICNICC) clinical decision rule (CDR) that predicts microbiologically documented infection (MDI) in children with cancer and fever and neutropenia (FN). We also investigated costs associated with current FN management strategies in Australia. METHODS: Demographic, episode, outcome and cost data were retrospectively collected on 650 episodes of FN. We assessed the discrimination, calibration, sensitivity and specificity of the PICNICC CDR in our cohort compared with the derivation data set. RESULTS: Using the original variable coefficients, the CDR performed poorly. After recalibration the PICNICC CDR had an area under the receiver operating characteristic (AUC-ROC) curve of 0.638 (95% CI 0.590-0.685) and calibration slope of 0.24. The sensitivity, specificity, positive predictive value and negative predictive value of the PICNICC CDR at presentation was 78.4%, 39.8%, 28.6% and 85.7%, respectively. For bacteraemia, the sensitivity improved to 85.2% and AUC-ROC to 0.71. Application at day 2, taking into consideration the proportion of MDI known (43%), further improved the sensitivity to 87.7%. Length of stay is the main contributor to cost of FN treatment, with an average cost per day of AUD 2183 in the low-risk group. CONCLUSIONS: For prediction of any MDI, the PICNICC rule did not perform as well at presentation in our cohort as compared with the derivation study. However, for bacteraemia, the predictive ability was similar to that of the derivation study, highlighting the importance of recalibration using local data. Performance also improved after an overnight period of observation. Implementation of a low-risk pathway, using the PICNICC CDR after a short period of inpatient observation, is likely to be safe and has the potential to reduce health-care expenditure.
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ItemPredicting Risk of Infection in Patients with Newly Diagnosed Multiple Myeloma: Utility of Immune Profiling(FRONTIERS MEDIA SA, 2017-10-05)BACKGROUND: A translational study in patients with myeloma to determine the utility of immune profiling to predict infection risk in patients with hematological malignancy was conducted. METHODS: Baseline, end of induction, and maintenance peripheral blood mononuclear cells from 40 patients were evaluated. Immune cell populations and cytokines released from 1 × 106 cells/ml cultured in the presence of a panel of stimuli (cytomegalovirus, influenza, S. pneumoniae, phorbol myristate acetate/ionomycin) and in media alone were quantified. Patient characteristics and infective episodes were captured from clinical records. Immunological variables associated with increased risk for infection in the 3-month period following sample collection were identified using univariate analysis (p < 0.05) and refined with multivariable analysis to define a predictive immune profile. RESULTS: 525 stimulant samples with 19,950 stimulant-cytokine combinations across three periods were studied, including 61 episodes of infection. Mitogen-stimulated release of IL3 and IL5 were significantly associated with increased risk for subsequent infection during maintenance therapy. A lower Th1/Th2 ratio and higher cytokine response ratios for IL5 and IL13 during maintenance therapy were also significantly associated with increased risk for infection. On multivariable analysis, only IL5 in response to mitogen stimulation was predictive of infection. The lack of cytokine response and numerical value of immune cells were not predictive of infection. CONCLUSION: Profiling cytokine release in response to mitogen stimulation can assist with predicting subsequent onset of infection in patients with hematological malignancy during maintenance therapy.
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ItemMicrobiome transplantation and modulation of immune related adverse events(ELSEVIER, 2019-02)
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ItemImplementation of a whole of hospital sepsis clinical pathway in a cancer hospital: impact on sepsis management, outcomes and costs.(BMJ, 2018)UNLABELLED: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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<0.05). Time to antibiotics was halved (55 vs 110 min, p<0.05). 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<0.05). 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. CONCLUSIONS: 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.
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ItemBeta-Lactam and Sulfonamide Allergy Testing Should Be a Standard of Care in Immunocompromised Hosts(ELSEVIER, 2019)Antibiotic allergies are reported in up to 1 in 4 immunocompromised hosts with significant impacts on antibiotic utilization and patient outcomes. Health services programs focused on de-labeling beta-lactam and sulfonamide allergy labels should be a standard of care in immunocompromised hosts.