Sir Peter MacCallum Department of Oncology - Theses
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ItemAntimicrobials in hospitalised and high-risk children: understanding and improving use( 2021)Infection is a near-universal human experience and is responsible for substantial child mortality across the globe, despite impressive reductions in child mortality and morbidity since the twentieth century. Antibiotics and other antimicrobial drugs have transformed our ability to prevent and treat infection. In general, these drugs are so safe, effective and widely available that overuse and inappropriate use are common. This is a cause of real problems in hospitals and the community, with unintended consequences of antimicrobial use including rising antimicrobial resistance. Antimicrobial stewardship (AMS) is aimed at improving the safety and efficacy of prescribing and has received growing attention in recent years. However, evidence to support and improve AMS for Australian children in hospitals is lacking. Australian hospitals are mandated to implement AMS programs and provide access to appropriate national and/or local prescribing guidelines. However, hospitals are under no current obligation to provide appropriately targeted AMS for the children in their care. Prior to mid-2019, national antimicrobial guidelines contained little paediatric and no neonatal advice. Since 2013, the voluntary National Antimicrobial Prescribing Survey (NAPS) has provided national reports on prescribing. However, until now, paediatric-specific data have not been reported. Compared with the literature on adult AMS, research on paediatric AMS is lacking, with few high-quality studies on interventions to improve care. This situation creates challenges for child healthcare providers and paediatric AMS program leaders, and more evidence is required to prioritise and improve care. The overall aims of this thesis are to improve the understanding of current antimicrobial use and stewardship for children in Australian hospitals and determine priorities to improve antimicrobial use now and in the future. This is achieved by analysing antimicrobial prescribing epidemiology and quality using national datasets, including national point prevalence survey and cohort study data. Chapter 1 reviews antimicrobial prescribing to children in hospitals, including in Australia. Chapter 2 presents the first analysis of paediatric antimicrobial prescribing to children in hospitals throughout Australia using NAPS data. Chapter 3 turns to high-risk groups, presenting the first nationwide analysis of prescribing for neonatal sepsis and fungal infections, again using NAPS data. Chapter 4 presents an analysis of antimicrobial prescribing in a contemporary cohort of immunocompromised children with fever and neutropenia, including prescribing quality and outcomes. Chapter 5 presents an interventional study evaluating the implementation of Australian guidelines on antibiotic duration and intravenous-to-oral switch. This is an example of the evidence translation and implementation approach needed for sustainable AMS improvement. Chapter 6 concludes the thesis, discussing the implications of the research and the paediatric AMS horizon in Australia. The analyses reported here reveal unnecessary variations in care and systemic inequities, which have implications for policy and guidelines. Non-metropolitan and non-tertiary hospitals in general provide lower-quality antimicrobial prescribing to children. This is likely to reflect decreased access to high-quality AMS resources, including guidelines and personnel, suggesting the need for systemic improvements. Neonates in Australian hospitals receive highly structured care in terms of antimicrobial choice and indications, but variations in dosing are substantial and undesirable, reflecting the lack of use of national guidelines. Prescribing for febrile neutropenia is highly diverse and often includes empiric aminoglycosides, which this research reveals are associated with real harm, suggesting the need for national guidelines to optimise care. Finally, the standard management of infections in hospitals involves excessive intravenous therapy, which is associated with unnecessarily increased hospital length of stay. As demonstrated, this can be improved with a structured AMS program, which should be available wherever children are treated in hospital. The information generated by this thesis provides new evidence on current antimicrobial prescribing practice and priorities and demonstrates the importance of utilising routinely collected data for the surveillance and improvement of paediatric AMS. Since this body of research began, national guidelines and paediatric-specific resources are now being developed, establishing new benchmarks. Along with continuous surveillance, these must be implemented appropriately to improve care. The research collaborations and networks developed during the production of this thesis will be used to support future surveillance and implementation work, which is needed to address AMS priorities in Australia and support the research and development of paediatric AMS across the globe.