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    [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
    Douglas, A ; Thursky, K ; Spelman, T ; Szer, J ; Bajel, A ; Harrison, S ; Tio, SY ; Bupha-Intr, O ; Tew, M ; Worth, L ; Teh, B ; Chee, L ; Ng, A ; Carney, D ; Khot, A ; Haeusler, G ; Yong, M ; Trubiano, J ; Chen, S ; Hicks, R ; Ritchie, D ; Slavin, M (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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    Evaluating peripheral intravascular catheter insertion, maintenance and removal practices in small hospitals using a standardized audit tool
    Hoskins, A ; Worth, LJ ; Malloy, MJ ; Smith, M ; Atkins, S ; Bennett, N (WILEY, 2022-05)
    AIM: The aim of this study was to evaluate clinical practice about peripheral intravenous catheter (PIVC) insertion, maintenance and removal in a cohort of Victorian hospitals. DESIGN: A standardized PIVC audit tool was developed, and results from point prevalent surveys were conducted. METHODS: Hospitalized patients requiring a PIVC insertion were eligible for audit. Audit data submitted between 2015 and 2019 were extracted for the current study. RESULTS: 3566 PIVC insertions in 15 Victorian public hospitals were evaluated. 57.6% of PIVCs were inserted in wards, 18.7% in operating theatres and 11.6% in Emergency Departments (ED). 45.2% were inserted by nurses and 38.2% by medical staff. The preferred site for insertion was the dorsum of the hand and forearm (58.8%). 22.6% did not report a visual infusion phlebitis score at least daily, and 48% did not document a daily dressing assessment. Reasons for PIVC removal included no longer required (63%) and phlebitis (4.8%). No bloodstream infections were reported.
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    In-hospital hyperglycemia but not diabetes mellitus alone is associated with increased in-hospital mortality in community-acquired pneumonia (CAP): systematic review and meta-analysis of observational studies prior to COVID-19
    Barmanray, RD ; Cheuk, N ; Fourlanos, S ; Greenberg, PB ; Colman, PG ; Worth, LJ (BMJ PUBLISHING GROUP, 2022-07)
    The objective of this review was to quantify the association between diabetes, hyperglycemia, and outcomes in patients hospitalized for community-acquired pneumonia (CAP) prior to the COVID-19 pandemic by conducting a systematic review and meta-analysis. Two investigators independently screened records identified in the PubMed (MEDLINE), EMBASE, CINAHL, and Web of Science databases. Cohort and case-control studies quantitatively evaluating associations between diabetes and in-hospital hyperglycemia with outcomes in adults admitted to hospital with CAP were included. Quality was assessed using the Newcastle-Ottawa Quality Assessment Scale, effect size using random-effects models, and heterogeneity using I2 statistics. Thirty-eight studies met the inclusion criteria. Hyperglycemia was associated with in-hospital mortality (adjusted OR 1.28, 95% CI 1.09 to 1.50) and intensive care unit (ICU) admission (crude OR 1.82, 95% CI 1.17 to 2.84). There was no association between diabetes status and in-hospital mortality (adjusted OR 1.04, 95% CI 0.72 to 1.51), 30-day mortality (adjusted OR 1.13, 95% CI 0.77 to 1.67), or ICU admission (crude OR 1.91, 95% CI 0.74 to 4.95). Diabetes was associated with increased mortality in all studies reporting >90-day postdischarge mortality and with longer length of stay only for studies reporting crude (OR 1.50, 95% CI 1.11 to 2.01) results. In adults hospitalized with CAP, in-hospital hyperglycemia but not diabetes alone is associated with increased in-hospital mortality and ICU admission. Diabetes status is associated with increased >90-day postdischarge mortality. Implications for management are that in-hospital hyperglycemia carries a greater risk for in-hospital morbidity and mortality than diabetes alone in patients admitted with non-COVID-19 CAP. Evaluation of strategies enabling timely and effective management of in-hospital hyperglycemia in CAP is warranted.
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    High influenza vaccination uptake in Victorian healthcare workers in 2020
    Lim, L-L ; Hoskins, AJ ; Worth, LJ ; Walker, KC ; Bull, AL ; Bennett, N (AUSTRALIAN GOVERNMENT, DEPT HEALTH & AGEING, 2021-07-22)
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    Pilot study of a combined genomic and epidemiologic surveillance program for hospital-acquired multidrug-resistant pathogens across multiple hospital networks in Australia
    Sherry, NL ; Lee, RS ; Gorrie, CL ; Kwong, JC ; Stuart, RL ; Korman, TM ; Marshall, C ; Higgs, C ; Chan, HT ; Graham, M ; Johnson, PDR ; Leroi, MJ ; Reed, C ; Richards, MJ ; Slavin, MA ; Worth, LJ ; Howden, BP ; Grayson, ML (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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    Influenza vaccination in aged care: improving uptake
    Bennett, NJ ; Hoskins, A ; Worth, LJ (WILEY, 2021-03)
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    Epidemiology of bloodstream infections in patients with myeloma receiving current era therapy
    Teh, BW ; Harrison, SJ ; Slavin, MA ; Worth, LJ (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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    Factors associated with antimicrobial choice for surgical prophylaxis in Australia
    Ierano, C ; Thursky, K ; Peel, T ; Koning, S ; James, R ; Johnson, S ; Hall, L ; Worth, LJ ; Marshall, C (OXFORD UNIV PRESS, 2020-09)
    BACKGROUND: Cefazolin is the most commonly recommended antimicrobial for surgical antimicrobial prophylaxis (SAP). However, the Australian Surgical National Antimicrobial Prescribing Survey revealed a wide range of antimicrobials prescribed for SAP. Inappropriate use of broad-spectrum antimicrobials is associated with increased patient harm and is a posited driver for antimicrobial resistance. OBJECTIVES: To describe patient, hospital and surgical factors that are associated with appropriateness of the top five prescribed antimicrobials/antimicrobial classes for procedural SAP. METHODS: All procedures audited from 18 April 2016 to 15 April 2019 in the Surgical National Antimicrobial Prescribing Survey were included in the analysis. Estimated marginal means analyses accounted for a range of variables and calculated a rate of adjusted appropriateness (AA). Subanalyses of the top five audited antimicrobials/antimicrobial classes identified associations between variables and appropriateness. RESULTS: A total of 12 419 surgical episodes with 14 150 prescribed initial procedural doses were included for analysis. When procedural SAP was prescribed, appropriateness was low (57.7%). Allergy status, surgical procedure group and the presence of prosthetic material were positively associated with cefazolin and aminoglycoside appropriateness (P < 0.05). There were no significant positive associations with glycopeptides and third/fourth-generation cephalosporins. The use of broad-spectrum antimicrobials was the most common reason for inappropriate choice (67.9% of metronidazole to 83.3% of third/fourth-generation cephalosporin prescriptions). CONCLUSIONS: Various factors influence appropriateness of procedural SAP choice. Identification of these factors provides targets for antimicrobial stewardship interventions, e.g. procedures where surgeons are regularly prescribing broad-spectrum SAP. These can be tailored to address local hospital prescribing practices.
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    Diagnosis, management and prevention of Candida auris in hospitals: position statement of the Australasian Society for Infectious Diseases
    Ong, CW ; Chen, SC-A ; Clark, JE ; Halliday, CL ; Kidd, SE ; Marriott, DJ ; Marshall, CL ; Morris, AJ ; Morrissey, CO ; Roy, R ; Slavin, MA ; Stewardson, AJ ; Worth, LJ ; Heath, CH (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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    Access, 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
    Douglas, AP ; Thursky, KA ; Worth, LJ ; Harrison, SJ ; Hicks, RJ ; Slavin, MA (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.