Infectious Diseases - Research Publications

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    Antimicrobial stewardship in Australia: the role of qualitative research in programme development
    Thursky, KA ; Hardefeldt, LY ; Rajkhowa, A ; Ierano, C ; Bishop, J ; Hawes, L ; Biezen, R ; Saha, SK ; Dowson, L ; Bailey, KE ; Scarborough, R ; Little, SB ; Gotterson, F ; Hur, B ; Khanina, A ; Urbancic, K ; Crabb, HK ; Richards, S ; Sri, A ; James, R ; Kong, DCM ; Marshall, C ; Mazza, D ; Peel, T ; Stuart, RL ; Manski-Nankervis, J-A ; Friedman, ND ; Bennett, N ; Schulz, T ; Billman-Jacobe, H ; Buono, E ; Worth, L ; Bull, A ; Richards, M ; Ayton, D ; Gilkerson, JR ; Browning, GF ; Buising, KL (OXFORD UNIV PRESS, 2021-09-30)
    Antimicrobial stewardship (AMS) in Australia is supported by a number of factors, including enabling national policies, sectoral clinical governance frameworks and surveillance programmes, clinician-led educational initiatives and health services research. A One Health research programme undertaken by the National Centre for Antimicrobial Stewardship (NCAS) in Australia has combined antimicrobial prescribing surveillance with qualitative research focused on developing antimicrobial use-related situational analyses and scoping AMS implementation options across healthcare settings, including metropolitan hospitals, regional and rural hospitals, aged care homes, general practice clinics and companion animal and agricultural veterinary practices. Qualitative research involving clinicians across these diverse settings in Australia has contributed to improved understanding of contextual factors that influence antimicrobial prescribing, and barriers and facilitators of AMS implementation. This body of research has been underpinned by a commitment to supplementing 'big data' on antimicrobial prescribing practices, where available, with knowledge of the sociocultural, technical, environmental and other factors that shape prescribing behaviours. NCAS provided a unique opportunity for exchange and cross-pollination across the human and animal health programme domains. It has facilitated synergistic approaches to AMS research and education, and implementation of resources and stewardship activities. The NCAS programme aimed to synergistically combine quantitative and qualitative approaches to AMS research. In this article, we describe the qualitative findings of the first 5 years.
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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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    Candida auris in an Australian health care facility: importance of screening high risk patients
    Worth, LJ ; Harrison, SJ ; Dickinson, M ; van Diemen, A ; Breen, J ; Harper, S ; Marshall, C ; Williamson, DA ; Thursky, KA ; Slavin, MA (WILEY, 2020-06)
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    Managing haematology and oncology patients during the COVID-19 pandemic: interim consensus guidance
    Weinkove, R ; McQuilten, ZK ; Adler, J ; Agar, MR ; Blyth, E ; Cheng, AC ; Conyers, R ; Haeusler, GM ; Hardie, C ; Jackson, C ; Lane, SW ; Middlemiss, T ; Mollee, P ; Mulligan, SP ; Ritchie, D ; Ruka, M ; Solomon, B ; Szer, J ; Thursky, KA ; Wood, EM ; Worth, LJ ; Yong, MK ; Slavin, MA ; Teh, BW (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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    Sepsis in cancer: a question of definition
    Valentine, JC ; Thursky, KA ; Worth, LJ (WILEY, 2020-06)
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    Classification performance of administrative coding data for detection of invasive fungal infection in paediatric cancer patients
    Valentine, JC ; Worth, LJ ; Verspoor, KM ; Hall, L ; Yeoh, DK ; Thursky, KA ; Clark, JE ; Haeusler, GM ; Vicha, A (PUBLIC LIBRARY SCIENCE, 2020-09-09)
    BACKGROUND: Invasive fungal infection (IFI) detection requires application of complex case definitions by trained staff. Administrative coding data (ICD-10-AM) may provide a simplified method for IFI surveillance, but accuracy of case ascertainment in children with cancer is unknown. OBJECTIVE: To determine the classification performance of ICD-10-AM codes for detecting IFI using a gold-standard dataset (r-TERIFIC) of confirmed IFIs in paediatric cancer patients at a quaternary referral centre (Royal Children's Hospital) in Victoria, Australia from 1st April 2004 to 31st December 2013. METHODS: ICD-10-AM codes denoting IFI in paediatric patients (<18-years) with haematologic or solid tumour malignancies were extracted from the Victorian Admitted Episodes Dataset and linked to the r-TERIFIC dataset. Sensitivity, positive predictive value (PPV) and the F1 scores of the ICD-10-AM codes were calculated. RESULTS: Of 1,671 evaluable patients, 113 (6.76%) had confirmed IFI diagnoses according to gold-standard criteria, while 114 (6.82%) cases were identified using the codes. Of the clinical IFI cases, 68 were in receipt of ≥1 ICD-10-AM code(s) for IFI, corresponding to an overall sensitivity, PPV and F1 score of 60%, respectively. Sensitivity was highest for proven IFI (77% [95% CI: 58-90]; F1 = 47%) and invasive candidiasis (83% [95% CI: 61-95]; F1 = 76%) and lowest for other/unspecified IFI (20% [95% CI: 5.05-72%]; F1 = 5.00%). The most frequent misclassification was coding of invasive aspergillosis as invasive candidiasis. CONCLUSION: ICD-10-AM codes demonstrate moderate sensitivity and PPV to detect IFI in children with cancer. However, specific subsets of proven IFI and invasive candidiasis (codes B37.x) are more accurately coded.
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    Consensus guidelines for antifungal prophylaxis in haematological malignancy and haemopoietic stem cell transplantation, 2021
    Teh, BW ; Yeoh, DK ; Haeusler, GM ; Yannakou, CK ; Fleming, S ; Lindsay, J ; Slavin, MA (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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    Consensus 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
    Chau, MM ; Daveson, K ; Alffenaar, J-WC ; Gwee, A ; Ho, SA ; Marriott, DJE ; Trubiano, JA ; Zhao, J ; Roberts, JA (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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    Introduction to the updated Australasian consensus guidelines for the management of invasive fungal disease and use of antifungal agents in the haematology/oncology setting, 2021
    Chang, CC ; Blyth, CC ; Chen, SC-A ; Khanina, A ; Morrissey, CO ; Roberts, JA ; Thursky, KA ; Worth, LJ ; Slavin, MA (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.