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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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ItemEpidemiology of bloodstream infections in patients with myeloma receiving current era therapy(WILEY-BLACKWELL, 2017-02)BACKGROUND: 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). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
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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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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 AvailableRisks and burden of viral respiratory tract infections in patients with multiple myeloma in the era of immunomodulatory drugs and bortezomib: experience at an Australian Cancer Hospital(SPRINGER, 2015-07)INTRODUCTION: Infections are a leading cause of morbidity and mortality in patients with multiple myeloma. The epidemiology, risk factors and outcomes of viral respiratory tract infections (vRTI) are not well described in patients with multiple myeloma managed with novel agents, the current standard of care. METHODS: Patients with myeloma from 2009 to 2012 who tested positive on respiratory virus multiplex polymerase chain reaction had clinical, radiological and microbiological records reviewed. The Fourth European Conference on Infections in Leukaemia (ECIL-4) definitions of RTI were applied. Univariate and multivariate regression analysis of risk factors was performed using vRTI as the evaluable outcome. RESULTS: Of 330 patients, 75 (22.7%) tested positive for a total of 100 vRTI episodes. All patients received thalidomide, lenalidomide or bortezomib in combination with myeloma therapies (median of three treatment regimens). vRTI occurred most commonly in patients with progressive disease, and receipt of more than three lines of myeloma therapy was associated with an increased risk of vRTI (p < 0.01). Amongst key respiratory pathogens, influenza was associated with the highest hospital admission rate (66.7%), ICU admission rate (41.6%) and mortality (33.3%) whilst RSV was associated with prolonged hospital stay. CONCLUSION: Patients with multiple myeloma and advanced disease managed with multiple lines of therapy are at risk for vRTI, and targeted interventions for prevention/treatment are required.
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ItemOseltamivir Resistance in Adult Oncology and Hematology Patients Infected with Pandemic (H1N1) 2009 Virus, Australia(CENTERS DISEASE CONTROL, 2010-07)We describe laboratory-confirmed influenza A pandemic (H1N1) 2009 in 17 hospitalized recipients of a hematopoietic stem cell transplant (HSCT) (8 allogeneic) and in 15 patients with malignancy treated at 6 Australian tertiary centers during winter 2009. Ten (31.3%) patients were admitted to intensive care, and 9 of them were HSCT recipients. All recipients of allogeneic HSCT with infection <100 days posttransplantation or severe graft-versus-host disease were admitted to an intensive care unit. In-hospital mortality rate was 21.9% (7/32). The H275Y neuraminidase mutation, which confers oseltamivir resistance developed in 4 of 7 patients with PCR positive for influenza after > or = 4 days of oseltamivir therapy. Three of these 4 patients were critically ill. Oseltamivir resistance in 4 (13.3%) of 30 patients who were administered oseltamivir highlights the need for ongoing surveillance of such resistance and further research on optimal antiviral therapy in the immunocompromised.
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ItemAn analysis of the utilisation of chemoprophylaxis against Pneumocystis jirovecii pneumonia in patients with malignancy receiving corticosteroid therapy at a cancer hospital(NATURE PUBLISHING GROUP, 2005-03-14)Pneumocystis jirovecii pneumonia (PCP) is associated with high mortality in immunocompromised patients without human immunodeficiency virus infection. However, chemoprophylaxis is highly effective. In patients with solid tumours or haematologic malignancy, several risk factors for developing PCP have been identified, predominantly corticosteroid therapy. The aims of this study were to identify the potentially preventable cases of PCP in patients receiving corticosteroid therapy at a tertiary care cancer centre and to estimate the frequency of utilisation of chemoprophylaxis in these patients. Two retrospective reviews were performed. Over a 10-year period, 14 cases of PCP were identified: no cases were attributable to failed chemoprophylaxis, drug allergy or intolerance. During a 6-month period, 73 patients received high-dose corticosteroid therapy (> or =25 mg prednisolone or > or =4 mg dexamethasone daily) for > or =4 weeks. Of these, 22 (30%) had haematologic malignancy, and 51 (70%) had solid tumours. Fewer patients with solid tumours received prophylaxis compared to patients with haematologic malignancy (3.9 vs 63.6%, P<0.0001). Guidelines for PCP chemoprophylaxis in patients with haematologic malignancy or solid tumours who receive corticosteroid therapy are proposed. Successful primary prevention of PCP in this population will require a multifaceted approach targeting the suboptimal prescribing patterns for chemoprophylaxis.