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Item[18F]FDG-PET-CT compared with CT for persistent or recurrent neutropenic fever in high-risk patients (PIPPIN): a multicentre, open-label, phase 3, randomised, controlled trial(ELSEVIER SCI LTD, 2022-08)BACKGROUND: Management of neutropenic fever in high-risk haematology patients is challenging; there are often few localising clinical features, and diagnostic tests have poor sensitivity and specificity. We aimed to compare how [18F]flurodeoxyglucose ([18F]FDG)-PET-CT scans and conventional CT scans affected the guidance of antimicrobial management and the outcomes of patients with persistent or recurrent neutropenic fever. METHODS: We did a multicentre, open-label, phase 3, randomised, controlled trial in two tertiary referral hospitals in Australia. We recruited adults aged 18 years or older who were receiving conditioning chemotherapy for haematopoietic stem-cell transplantation or chemotherapy for acute leukaemia and had persistent (>72 h) or recurrent (new fever beyond 72 h of initial onset interspersed with >48 h defervescence) neutropenic fever. Exclusion criteria were pregnancy, allergy to iodinated contrast, or estimated glomerular filtration rate of less than 30 mL/min. Patients were randomly assigned by computer-generated randomisation chart (1:1) to [18F]FDG-PET-CT or conventional CT. Masking was not possible because of the nature of the investigation. Scans were done within 3 days of random assignment. The primary endpoint was a composite of starting, stopping, or changing the spectrum (broadening or narrowing) of antimicrobial therapy-referred to here as antimicrobial rationalisation-within 96 h of the assigned scan, analysed per protocol. This trial is registered with clinicaltrials.gov, NCT03429387, and is complete. FINDINGS: Between Jan 8, 2018, and July 23, 2020, we assessed 316 patients for eligibility. 169 patients were excluded and 147 patients were randomly assigned to either [18F]FDG-PET-CT (n=73) or CT (n=74). Nine patients did not receive a scan per protocol, and two participants in each group were excluded for repeat entry into the study. 65 patients received [18F]FDG-PET-CT (38 [58%] male; 53 [82%] White) and 69 patients received CT (50 [72%] male; 58 [84%] White) per protocol. Median follow up was 6 months (IQR 6-6). Antimicrobial rationalisation occurred in 53 (82%) of 65 patients in the [18F]FDG-PET-CT group and 45 (65%) of 69 patients in the CT group (OR 2·36, 95% CI 1·06-5·24; p=0·033). The most frequent component of antimicrobial rationalisation was narrowing spectrum of therapy, in 28 (43%) of 65 patients in the [18F]FDG-PET-CT group compared with 17 (25%) of 69 patients in the CT group (OR 2·31, 95% CI 1·11-4·83; p=0·024). INTERPRETATION: [18F]FDG-PET-CT was associated with more frequent antimicrobial rationalisation than conventional CT. [18F]FDG-PET-CT can support decision making regarding antimicrobial cessation or de-escalation and should be considered in the management of patients with haematological diseases and persistent or recurrent high-risk neutropenic fever after chemotherapy or transplant conditioning. FUNDING: National Health and Medical Research Council Centre of Research Excellence (APP1116876), Melbourne Health foundation, Gilead Research Fellowship grants supported this study.
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ItemPilot study of a combined genomic and epidemiologic surveillance program for hospital-acquired multidrug-resistant pathogens across multiple hospital networks in Australia(CAMBRIDGE UNIV PRESS, 2021-05)OBJECTIVES: To conduct a pilot study implementing combined genomic and epidemiologic surveillance for hospital-acquired multidrug-resistant organisms (MDROs) to predict transmission between patients and to estimate the local burden of MDRO transmission. DESIGN: Pilot prospective multicenter surveillance study. SETTING: The study was conducted in 8 university hospitals (2,800 beds total) in Melbourne, Australia (population 4.8 million), including 4 acute-care, 1 specialist cancer care, and 3 subacute-care hospitals. METHODS: All clinical and screening isolates from hospital inpatients (April 24 to June 18, 2017) were collected for 6 MDROs: vanA VRE, MRSA, ESBL Escherichia coli (ESBL-Ec) and Klebsiella pneumoniae (ESBL-Kp), and carbapenem-resistant Pseudomonas aeruginosa (CRPa) and Acinetobacter baumannii (CRAb). Isolates were analyzed and reported as routine by hospital laboratories, underwent whole-genome sequencing at the central laboratory, and were analyzed using open-source bioinformatic tools. MDRO burden and transmission were assessed using combined genomic and epidemiologic data. RESULTS: In total, 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%). Most MDROs (88.3%) were isolated from patients with recent healthcare exposure.Combining genomics and epidemiology identified that at least 27.1% of MDROs were likely acquired in a hospital; most of these transmission events would not have been detected without genomics. The highest proportion of transmission occurred with vanA VRE (88.4% of patients). CONCLUSIONS: Genomic and epidemiologic data from multiple institutions can feasibly be combined prospectively, providing substantial insights into the burden and distribution of MDROs, including in-hospital transmission. This analysis enables infection control teams to target interventions more effectively.
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ItemNo Preview AvailableManaging haematology and oncology patients during the COVID-19 pandemic: interim consensus guidance(WILEY, 2020-06)INTRODUCTION: A pandemic coronavirus, SARS-CoV-2, causes COVID-19, a potentially life-threatening respiratory disease. Patients with cancer may have compromised immunity due to their malignancy and/or treatment, and may be at elevated risk of severe COVID-19. Community transmission of COVID-19 could overwhelm health care services, compromising delivery of cancer care. This interim consensus guidance provides advice for clinicians managing patients with cancer during the pandemic. MAIN RECOMMENDATIONS: During the COVID-19 pandemic: In patients with cancer with fever and/or respiratory symptoms, consider causes in addition to COVID-19, including other infections and therapy-related pneumonitis. For suspected or confirmed COVID-19, discuss temporary cessation of cancer therapy with a relevant specialist. Provide information on COVID-19 for patients and carers. Adopt measures within cancer centres to reduce risk of nosocomial SARS-CoV-2 acquisition; support population-wide social distancing; reduce demand on acute services; ensure adequate staffing; and provide culturally safe care. Measures should be equitable, transparent and proportionate to the COVID-19 threat. Consider the risks and benefits of modifying cancer therapies due to COVID-19. Communicate treatment modifications, and review once health service capacity allows. Consider potential impacts of COVID-19 on the blood supply and availability of stem cell donors. Discuss and document goals of care, and involve palliative care services in contingency planning. CHANGES IN MANAGEMENT AS A RESULT OF THIS STATEMENT: This interim consensus guidance provides a framework for clinicians managing patients with cancer during the COVID-19 pandemic. In view of the rapidly changing situation, clinicians must also monitor national, state, local and institutional policies, which will take precedence. ENDORSED BY: Australasian Leukaemia and Lymphoma Group; Australasian Lung Cancer Trials Group; Australian and New Zealand Children's Haematology/Oncology Group; Australia and New Zealand Society of Palliative Medicine; Australasian Society for Infectious Diseases; Bone Marrow Transplantation Society of Australia and New Zealand; Cancer Council Australia; Cancer Nurses Society of Australia; Cancer Society of New Zealand; Clinical Oncology Society of Australia; Haematology Society of Australia and New Zealand; National Centre for Infections in Cancer; New Zealand Cancer Control Agency; New Zealand Society for Oncology; and Palliative Care Australia.
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ItemIncursions of Candida auris into Australia, 2018(CENTERS DISEASE CONTROL & PREVENTION, 2020-06)Candida auris is an emerging global healthcare-associated pathogen. During July-December 2018, four patients with C. auris were identified in Victoria, Australia, all with previous overseas hospitalization. Phylogenetic analysis revealed putative transmission between 2 patients and suspected overseas acquisition in the others. Vigilant screening of at-risk patients is required.
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ItemInvasive pulmonary aspergillosis in critically ill patients with COVID-19 in Australia: implications for screening and treatment(WILEY, 2021-12)We report four cases of invasive pulmonary aspergillus co-infection in patients with coronavirus disease 2019 (COVID-19) infection and acute respiratory distress syndrome requiring intensive care unit (ICU) admission. Aspergillus fumigatus and Aspergillus terreus were isolated, with early infection onset following ICU admission. Clinicians should be aware of invasive pulmonary aspergillosis in ICU patients with COVID-19 infection, particularly those receiving dexamethasone. We propose screening of these high-risk patients with twice-weekly fungal culture from tracheal aspirate and, if feasible, Aspergillus polymerase chain reaction. Diagnosis is challenging and antifungal treatment should be considered in critically ill patients who have new or worsening pulmonary changes on chest imaging and mycological evidence of infection.
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ItemConsensus guidelines for antifungal prophylaxis in haematological malignancy and haemopoietic stem cell transplantation, 2021(WILEY, 2021-11)Antifungal prophylaxis can reduce morbidity and mortality from invasive fungal disease (IFD). However, its use needs to be optimised and appropriately targeted to patients at highest risk to derive the most benefit. In addition to established risks for IFD, considerable recent progress in the treatment of malignancies has resulted in the development of new 'at-risk' groups. The changing epidemiology of IFD and emergence of drug resistance continue to impact choice of prophylaxis, highlighting the importance of active surveillance and knowledge of local epidemiology. These guidelines aim to highlight emerging risk groups and review the evidence and limitations around new formulations of established agents and new antifungal drugs. It provides recommendations around use and choice of antifungal prophylaxis, discusses the potential impact of the changing epidemiology of IFD and emergence of drug resistance, and future directions for risk stratification to assist optimal management of highly vulnerable patients.
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ItemConsensus guidelines for optimising antifungal drug delivery and monitoring to avoid toxicity and improve outcomes in patients with haematological malignancy and haemopoietic stem cell transplant recipients, 2021(WILEY, 2021-11)Antifungal agents can have complex dosing and the potential for drug interaction, both of which can lead to subtherapeutic antifungal drug concentrations and poorer clinical outcomes for patients with haematological malignancy and haemopoietic stem cell transplant recipients. Antifungal agents can also be associated with significant toxicities when drug concentrations are too high. Suboptimal dosing can be minimised by clinical assessment, laboratory monitoring, avoidance of interacting drugs, and dose modification. Therapeutic drug monitoring (TDM) plays an increasingly important role in antifungal therapy, particularly for antifungal agents that have an established exposure-response relationship with either a narrow therapeutic window, large dose-exposure variability, cytochrome P450 gene polymorphism affecting drug metabolism, the presence of antifungal drug interactions or unexpected toxicity, and/or concerns for non-compliance or inadequate absorption of oral antifungals. These guidelines provide recommendations on antifungal drug monitoring and TDM-guided dosing adjustment for selected antifungal agents, and include suggested resources for identifying and analysing antifungal drug interactions. Recommended competencies for optimal interpretation of antifungal TDM and dose recommendations are also provided.
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ItemIntroduction to the updated Australasian consensus guidelines for the management of invasive fungal disease and use of antifungal agents in the haematology/oncology setting, 2021(WILEY, 2021-11)This article introduces the fourth update of the Australian and New Zealand consensus guidelines for the management of invasive fungal disease and use of antifungal agents in the haematology/oncology setting. These guidelines are comprised of nine articles as presented in this special issue of the Internal Medicine Journal. This introductory chapter outlines the rationale for the current update and the steps taken to ensure implementability in local settings. Given that 7 years have passed since the previous iteration of these guidelines, pertinent contextual changes that impacted guideline content and recommendations are discussed, including the evolution of invasive fungal disease (IFD) definitions. We also outline our approach to guideline development, evidence grading, review and feedback. Highlights of the 2021 update are presented, including expanded scope to provide more detailed coverage of common and emerging fungi such as Aspergillus and Candida species, and emerging fungi, and a greater focus on the principles of antifungal stewardship. We also introduce an entirely new chapter dedicated to helping healthcare workers convey important concepts related to IFD, infection prevention and antifungal therapy, to patients.
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ItemEpidemiology, treatment and outcomes of bloodstream infection due to vancomycin-resistant enterococci in cancer patients in a vanB endemic setting(Springer Nature, 2020-03-18)Background: 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. Methods: 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. Results: 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. Conclusions: 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.