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OBJECTIVES: Dentists manage a variety of oral infections in clinical practice. Inappropriate antimicrobial prescribing by dentists occurs frequently and antimicrobial stewardship strategies should include dentistry. The aim of this retrospective analysis of the Australian Hospital National Antimicrobial Prescribing Survey (Hospital NAPS) dataset, was to describe the types of oral and dental indications where antimicrobials were prescribed, and assess the guideline compliance and appropriateness of the antimicrobials in Australian hospitals. METHODS: Data from the Hospital NAPS was extracted for oral and dental indications from 2013 to 2022. The types of oral and dental indications presented, and the corresponding antimicrobials prescribed were assessed for compliance according to national prescribing guidelines, and appropriateness according to the NAPS structured algorithm. RESULTS: A total of 8,001 prescriptions for 7,477 patients were identified, from 433 hospitals. Antifungal, antibiotic and antiviral agents accounted for 84.5 %, 15.4 % and 0.03 % of prescriptions respectively. A greater proportion of antibiotics were prescribed in regional and rural areas compared to antifungals. The prescriptions assessed as compliant were 80.0 % and 44.7 % of antifungals and antibiotics respectively. Prescriptions assessed as appropriate were 84.4 % of antifungals, and 65.3 % of antibiotic prescriptions. CONCLUSIONS: A wide variety of antimicrobials were used with moderate levels of compliance and appropriateness. Future interventions should include targeted education, utilisation of prescribing guidelines, and tools to diagnose and manage oral and dental conditions. Consideration can be given to adjustment of the Hospital NAPS tool to cater for oral conditions and include the provision of dental treatment in the management of these infections. CLINICAL SIGNIFICANCE: A wide variety of oral and dental conditions are presented in Australian hospital settings, managed by a range

Objectives Residents of long-term care facilities (LTCFs) are especially vulnerable to acquiring healthcare-associated infections (HAIs). Our systematic review and meta-analysis estimated the burden of HAIs, identified the most frequent HAIs and explored the impact of facility-level and surveillance methodological differences on HAI burden in LTCFs, as determined by point prevalence studies (PPS). Design Systematic review and meta-analysis. Data sources Bibliographic databases MEDLINE (Ovid), Embase (Ovid) and CINAHL (EBSCOhost) were searched for potentially eligible English-language original research publications. References of short-listed full-text publications, the European Centre for Disease Control and Prevention website and an unpublished 2016–2022 Australian Aged Care PPS report were also checked. Eligibility criteria PPS monitoring HAIs, published and undertaken between January 1991 and June 2023 in LTCFs. Data extraction and synthesis Two reviewers independently screened for eligible PPS and if included, assessed risk of bias for each PPS using the Joanna Briggs Institute (JBI) critical appraisal tool for prevalence studies. Meta-analysis was performed using a generalised linear mixed model. Results 31 publications (including 123 PPS from 33 countries encompassing 709 860 residents) were included. Nine PPS (7.3%) were allocated a JBI quality score greater than 80% while 30 PPS (24.4%) were allocated a score between 70% and 80%. The overall pooled HAI point prevalence was 3.5% (95% CI 3.1% to 4.0%); 3.9% (95% CI 3.2% to 4.7%) when higher bias-risk PPS (<70% quality score) were excluded. Of 120 PPS, the most frequently reported HAIs were urinary tract (UTIs; 38.9%), respiratory tract (RTIs; 33.6%) and skin or soft tissue (SSTIs; 23.7%) infections. HAI point prevalence varied by geographical region (p<0.001), study decade (p<0.001) and HAI surveillance definitions used (p<0.001). There was no difference across facility types (p=0.57) or season (p=

BACKGROUND: Skin and soft tissue infections (SSTIs) are among the most common indications for antimicrobial prescribing in hospitals. Inappropriate antimicrobial use can lead to increased morbidity, unnecessary hospital re-admission and increased antimicrobial resistance. This study aimed to assess the quality of antimicrobial prescribing practices in SSTI management within Australian hospitals to provide guidance for future practice. METHODS: A retrospective analysis was conducted with data from the National Antimicrobial Prescribing Survey (NAPS). SSTI prescribing data from Hospital NAPS (2013-2022) and surgical site infection data from Surgical NAPS (2016-2022) datasets were analysed. Variables assessed included guideline compliance, appropriateness as per the structured NAPS algorithm, and reasons for inappropriateness. RESULTS: From the Hospital NAPS dataset, 40,535 antimicrobial prescriptions for SSTIs were analysed. The most common indication was cellulitis (34.1%, N=13,822), and the most prescribed antimicrobial was flucloxacillin (18.8%, N=7,638). SSTI indications had a lower rate of guideline compliance but a higher rate of appropriateness compared with all other indications for antimicrobial prescriptions (guideline compliance 66.3%, N=21,035 vs 67.4%, N=156,285; appropriateness 75.6%, N=30,639 vs 72.7%, N=209,383). The most common reason for inappropriateness was incorrect dose or frequency (29.3%, N=2367). From the Surgical NAPS dataset, 5674 prescriptions for surgical site infections were analysed. Of these, 68.2% (N=3867) were deemed to be appropriate. The most common reason for inappropriateness was incorrect dose or frequency (27.7%, N=350). CONCLUSIONS: As SSTIs are a common indication for prescribing an antimicrobial in Australian hospitals, identifying effective antimicrobial stewardship strategies to optimize antimicrobial use for SSTI management is recommended to improve patient outcomes.

Background Oral amoxicillin‐clavulanic acid, a broad‐spectrum antimicrobial and one of the most commonly prescribed antimicrobials in Australia, has demonstrated poor prescribing guideline compliance and appropriateness. This may have inadvertent impacts on patient care and safety, from adverse drug reactions to antimicrobial resistance. Intravenous (IV) amoxicillin‐clavulanic acid was first registered in Australia in 2017, reflecting a subsequent and immediate increase in use. There is a need to assess the quality of such prescribing. Aim To describe the quality of IV amoxicillin‐clavulanic acid prescriptions through assessing guideline compliance and appropriateness of use in Australian hospitals. Method A retrospective data analysis of IV amoxicillin‐clavulanic acid prescriptions from the Hospital National Antimicrobial Prescribing Survey database between 2013 and 2021. The main outcomes measured were guideline compliance and appropriateness. Results The proportion of prescriptions for IV amoxicillin‐clavulanic acid, compared to all other antimicrobials, increased from 0.02% (2013) to 2.3% (2021). Guideline compliance and appropriateness have overall decreased (by 18.9% and 16.7%, respectively). Over time, national guidelines predominantly replaced local guidelines as the primary guideline source for prescribing. The most common reason for inappropriateness was unnecessarily broad spectrum of activity (39.5%). Conclusion Intravenous amoxicillin‐clavulanic acid prescribing continues to increase throughout Australian hospitals, with notable reductions in guideline compliance and appropriateness. Since 2019, the increase in these outcomes coincided with updated national prescribing guidelines, evident by prescribers utilising national over local guidelines. These findings reinforce the concept that antimicrobial stewardship initiatives, including auditing, robust national guidelines and education, are crucial to optimise IV amoxicillin‐clavulanic acid presc

BACKGROUND: Febrile neutropenia (FN) in children with cancer generally requires in-hospital care, but low-risk patients may be successfully managed in an outpatient setting, potentially reducing the overall healthcare costs. Updated data on the costs of FN care are lacking. METHODS: A bottom-up microcosting analysis was conducted from the healthcare system perspective using data collected alongside the Australian PICNICC (Predicting Infectious Complications of Neutropenic sepsis In Children with Cancer) study. Inpatient costs were accessed from hospital administrative records and outpatient costs from Medicare data. Costs were stratified by risk status (low/high risk) according to the PICNICC criteria. Estimated mean costs were obtained through bootstrapping and using a linear model to account for multiple events across individuals and other clinical factors that may impact costs. RESULTS: The total costs of FN care were significantly higher for FN events classified as high-risk ($17,827, 95% confidence interval [CI]: $17,193-$18,461) compared to low-risk ($10,574, 95% CI: $9818-$11,330). In-hospital costs were significantly higher for high-risk compared to low-risk events, despite no differences in the cost structure, mean cost per day, and pattern of resource use. Hospital length of stay (LOS) was the only modifiable factor significantly associated with total costs of care. Excluding antineoplastics, antimicrobials are the most commonly used medications in the inpatient and outpatient setting for the overall period of analysis. CONCLUSION: The FN costs are driven by in-hospital admission and LOS. This suggests that the outpatient management of low-risk patients is likely to reduce the in-hospital cost of treating an FN event. Further research will determine if shifting the cost to the outpatient setting remains cost-effective overall.

BACKGROUND: Febrile neutropenia (FN) in children with cancer generally requires in-hospital care, but low-risk patients may be successfully managed in an outpatient setting, potentially reducing the overall healthcare costs. Updated data on the costs of FN care are lacking. METHODS: A bottom-up microcosting analysis was conducted from the healthcare system perspective using data collected alongside the Australian PICNICC (Predicting Infectious Complications of Neutropenic sepsis In Children with Cancer) study. Inpatient costs were accessed from hospital administrative records and outpatient costs from Medicare data. Costs were stratified by risk status (low/high risk) according to the PICNICC criteria. Estimated mean costs were obtained through bootstrapping and using a linear model to account for multiple events across individuals and other clinical factors that may impact costs. RESULTS: The total costs of FN care were significantly higher for FN events classified as high-risk ($17,827, 95% confidence interval [CI]: $17,193-$18,461) compared to low-risk ($10,574, 95% CI: $9818-$11,330). In-hospital costs were significantly higher for high-risk compared to low-risk events, despite no differences in the cost structure, mean cost per day, and pattern of resource use. Hospital length of stay (LOS) was the only modifiable factor significantly associated with total costs of care. Excluding antineoplastics, antimicrobials are the most commonly used medications in the inpatient and outpatient setting for the overall period of analysis. CONCLUSION: The FN costs are driven by in-hospital admission and LOS. This suggests that the outpatient management of low-risk patients is likely to reduce the in-hospital cost of treating an FN event. Further research will determine if shifting the cost to the outpatient setting remains cost-effective overall.

T/Natural killer (NK) cell lymphomas (TCL) represent a heterogenous subgroup of non-Hodgkin lymphoma, associated with poorer prognosis and higher treatment toxicity. A cohesive synthesis of infection outcomes among TCL patients is lacking. International guidelines offer no specific recommendations regarding prophylaxis or supportive infection care for TCL patients. This systematic narrative review highlights infection outcomes in TCL patients treated with conventional, and novel therapies. Recommendations for infection screening, antimicrobial prophylaxis and vaccination strategies are outined.

Infection remains a significant contributor to morbidity and mortality in patients with myeloma. This guideline was developed by a multidisciplinary group of clinicians who specialise in the management of patients with myeloma and infection from the medical and scientific advisory group from Myeloma Australia and the National Centre for Infections in Cancer. In addition to summarising the current epidemiology and risk factors for infection in patients with myeloma, this guideline provides recommendations that address three key areas in the prevention of infection: screening for latent infection, use of antimicrobial prophylaxis and immunoglobulin replacement and vaccination against leading respiratory infections (severe acute respiratory syndrome coronavirus 2, influenza and Streptococcus pneumoniae) and other preventable infections. This guideline provides a practical approach to the prevention of infection in patients with myeloma and harmonises the clinical approach to screening for infection, use of prophylaxis and vaccination to prevent infectious complications.

BACKGROUND: Febrile neutropenia (FN) in children with cancer generally requires in-hospital care, but low-risk patients may be successfully managed in an outpatient setting, potentially reducing the overall healthcare costs. Updated data on the costs of FN care are lacking. METHODS: A bottom-up microcosting analysis was conducted from the healthcare system perspective using data collected alongside the Australian PICNICC (Predicting Infectious Complications of Neutropenic sepsis In Children with Cancer) study. Inpatient costs were accessed from hospital administrative records and outpatient costs from Medicare data. Costs were stratified by risk status (low/high risk) according to the PICNICC criteria. Estimated mean costs were obtained through bootstrapping and using a linear model to account for multiple events across individuals and other clinical factors that may impact costs. RESULTS: The total costs of FN care were significantly higher for FN events classified as high-risk ($17,827, 95% confidence interval [CI]: $17,193-$18,461) compared to low-risk ($10,574, 95% CI: $9818-$11,330). In-hospital costs were significantly higher for high-risk compared to low-risk events, despite no differences in the cost structure, mean cost per day, and pattern of resource use. Hospital length of stay (LOS) was the only modifiable factor significantly associated with total costs of care. Excluding antineoplastics, antimicrobials are the most commonly used medications in the inpatient and outpatient setting for the overall period of analysis. CONCLUSION: The FN costs are driven by in-hospital admission and LOS. This suggests that the outpatient management of low-risk patients is likely to reduce the in-hospital cost of treating an FN event. Further research will determine if shifting the cost to the outpatient setting remains cost-effective overall.

BACKGROUND: Febrile neutropenia (FN) in children with cancer generally requires in-hospital care, but low-risk patients may be successfully managed in an outpatient setting, potentially reducing the overall healthcare costs. Updated data on the costs of FN care are lacking. METHODS: A bottom-up microcosting analysis was conducted from the healthcare system perspective using data collected alongside the Australian PICNICC (Predicting Infectious Complications of Neutropenic sepsis In Children with Cancer) study. Inpatient costs were accessed from hospital administrative records and outpatient costs from Medicare data. Costs were stratified by risk status (low/high risk) according to the PICNICC criteria. Estimated mean costs were obtained through bootstrapping and using a linear model to account for multiple events across individuals and other clinical factors that may impact costs. RESULTS: The total costs of FN care were significantly higher for FN events classified as high-risk ($17,827, 95% confidence interval [CI]: $17,193-$18,461) compared to low-risk ($10,574, 95% CI: $9818-$11,330). In-hospital costs were significantly higher for high-risk compared to low-risk events, despite no differences in the cost structure, mean cost per day, and pattern of resource use. Hospital length of stay (LOS) was the only modifiable factor significantly associated with total costs of care. Excluding antineoplastics, antimicrobials are the most commonly used medications in the inpatient and outpatient setting for the overall period of analysis. CONCLUSION: The FN costs are driven by in-hospital admission and LOS. This suggests that the outpatient management of low-risk patients is likely to reduce the in-hospital cost of treating an FN event. Further research will determine if shifting the cost to the outpatient setting remains cost-effective overall.

BACKGROUND AND OBJECTIVE: Inappropriate antimicrobial use can lead to adverse consequences, including antimicrobial resistance. The objective of our study was to describe patterns of prophylactic antimicrobial prescribing in Australian residential aged-care facilities and thereby provide insight into antimicrobial stewardship strategies that might be required. METHODS: Annual point prevalence data submitted by participating residential aged-care facilities as part of the Aged Care National Antimicrobial Prescribing Survey between 2016 and 2020 were extracted. All antimicrobials except anti-virals were counted; methenamine hippurate was classified as an antibacterial agent. RESULTS: The overall prevalence of residents prescribed one or more prophylactic antimicrobial on the survey day was 3.7% (n = 4643, 95% confidence interval 3.6-3.8). Of all prescribed antimicrobials (n = 15,831), 27.1% (n = 4871) were for prophylactic use. Of these prophylactic antimicrobials, 87.8% were anti-bacterials and 11.4% antifungals; most frequently, cefalexin (28.7%), methenamine hippurate (20.1%) and clotrimazole (8.8%). When compared with prescribing of all antimicrobial agents, prophylactic antimicrobials were less commonly prescribed for pro re nata administration (7.0% vs 20.3%) and more commonly prescribed greater than 6 months (52.9% vs 34.1%). The indication and review or stop date was less frequently documented (67.5% vs 73.8% and 20.9% vs 40.7%, respectively). The most common body system for which a prophylactic antimicrobial was prescribed was the urinary tract (54.3%). Of all urinary tract indications (n = 2575), about two thirds (n = 1681, 65.3%) were for cystitis and 10.6% were for asymptomatic bacteriuria. CONCLUSIONS: Our results clearly identified immediate antimicrobial stewardship strategies that aim to improve prophylactic antimicrobial prescribing in Australian residential-aged care facilities are required.

Interprofessional collaboration between general practitioners (GPs) and community pharmacists (CPs) is central to implement antimicrobial stewardship (AMS) programmes in primary care. This study aimed to design a GP/pharmacist antimicrobial stewardship (GPPAS) model for primary care in Australia. An exploratory study design was followed that included seven studies conducted from 2017 to 2021 for the development of the GPPAS model. We generated secondary and primary evidence through a systematic review, a scoping review, a rapid review, nationwide surveys of Australian GPs and CPs including qualitative components, and a pilot study of a GPPAS submodel. All study evidence was synthesised, reviewed, merged, and triangulated to design the prototype GPPAS model using a Systems Engineering Initiative for Patient Safety theoretical framework. The secondary evidence provided effective GPPAS interventions, and the primary evidence identified GP/CP interprofessional issues, challenges, and future needs for implementing GPPAS interventions. The framework of the GPPAS model informed five GPPAS implementation submodels to foster implementation of AMS education program, antimicrobial audits, diagnostic stewardship, delayed prescribing, and routine review of antimicrobial prescriptions, through improved GP-CP collaboration. The GPPAS model could be used globally as a guide for GPs and CPs to collaboratively optimise antimicrobial use in primary care. Implementation studies on the GPPAS model and submodels are required to integrate the GPPAS model into GP/pharmacist interprofessional care models in Australia for improving AMS in routine primary care.

The National Antimicrobial Prescribing Survey (NAPS) is a web-based, standardized tool, widely adopted in Australian healthcare facilities to assess the reasons for, the quantity of, and the quality of antimicrobial prescribing. It consists of multiple modules tailored towards the needs of a variety of healthcare facilities. Data regarding ophthalmological antimicrobial use from Hospital NAPS, Surgical NAPS, and Aged Care NAPS were analysed. In Hospital NAPS, the most common reasons for inappropriate prescribing were incorrect dose or frequency and incorrect duration. Prolonged duration was also common in Aged Care prescribing: about one quarter of all antimicrobials had been prescribed for greater than 6 months. All three modules found chloramphenicol to be the most prescribed antimicrobial with a high rate of inappropriate prescribing, usually for conjunctivitis.

BACKGROUND: Multi-disciplinary antimicrobial stewardship teams are a common strategy employed to optimise antimicrobial prescribing. Nurses play a pivotal role in patient care and safety; however, their role and potential opportunities across surgical antimicrobial stewardship are not well-established. This study aims to highlight health professional perspectives of the nurse's role and relevant opportunities for nurses to engage in and lead surgical antimicrobial stewardship initiatives. METHODS: An exploratory, multi-site, collective qualitative case study. Transcribed audio-recordings of focus groups with health professionals underwent thematic analysis, with mapping to established frameworks. RESULTS: Four key themes were identified; surgical antimicrobial prophylaxis is not prioritised for quality improvement, but nurses perceive benefits from surgical antimicrobial prophylaxis education and training; professional hierarchy hinders nurse engagement and leadership in antimicrobial stewardship; nurses are consistently engaged with patient care throughout the surgical journey; and clarity of roles and accountability for surgical antimicrobial prophylaxis review and follow-up can bolster quality improvement initiatives. DISCUSSION: Many opportunities exist for nurse engagement in surgical antimicrobial stewardship. Identification of barriers and enablers support theoretically informed strategies i.e., education and guideline accessibility; multidisciplinary collaborations; executive support for nursing capacity building and the standardisation of surgical antimicrobial prophylaxis workflow and documentation. CONCLUSIONS: Nurses are critical to patient safety and to supporting antimicrobial stewardship, in the operating theatre, and throughout the patient's surgical journey. Applying theoretical frameworks to understand barriers and enablers to nurses' contribution to antimicrobial stewardship has given insights to inform interventions to support nurse engagement.

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 [7

BACKGROUND: Antimicrobial stewardship (AMS) aims to optimize antimicrobial use. Auditing and reporting of antimicrobial prescribing are essential. Auditing tools for solid organ transplant (SOT) patients should tailor to their needs. METHODS: We reviewed published data describing auditing tools in the general and SOT population. RESULTS: We focused on three internationally or nationally available auditing tools. The National Antimicrobial Prescribing Survey (NAPS) is web-based tool to report antimicrobial consumption and assess appropriateness using standardized definitions based on consensus guidelines. In the absence of guidelines, adjudication is based on AMS principles. An automated dashboard, analyses by indication or antimicrobial, and benchmarking reports are available. The National Healthcare Safety Network Antimicrobial Use/Resistance module was developed by the Centers for Disease Control and Prevention for hospitals to upload monthly data, which are standardized for benchmarking. It does not assess appropriateness or address SOT wards. The Global-Point Prevalence Survey from bioMérieux collects data on antimicrobial regimen, indication and microbial resistance. Variables unique to SOT include comorbidities and devices. Assessment of appropriateness is limited to guideline adherence, and benchmarking may require prearrangement with bioMérieux. Benchmarking requires prearrangement. Advances in electronic health record systems and clinical decision support tools can improve the efficiency of the auditing process. CONCLUSION: Each AMS auditing tool has unique features for SOT patients. Capturing immunosuppression, source control, organ dysfunction, donor-derived infection, serology, and colonization status will enhance their applicability.

Abstract Background: Rising antimicrobial resistance (AMR) in primary care is a growing concern and a threat to community health. The rise of AMR can be slowed down if general practitioners (GPs) and community pharmacists (CPs) could work as a team to implement antimicrobial stewardship (AMS) programs for optimal use of antimicrobial(s). However, the evidence supporting a GP pharmacist collaborative AMS implementation model (GPPAS) in primary care remains limited. Aim: With an aim to design a GPPAS model in Australia, this paper outlines how this model will be developed. Methods: This exploratory study undertakes a systematic review, a scoping review, nationwide surveys, and qualitative interviews to design the model. Medical Research Council (MRC) framework and Normalization Process Theory are utilized as guides. Reviews will identify the list of effective GPPAS interventions. Two AMS surveys and paired interviews of GPs and CPs across Australia will explore their convergent and divergent views about the GPPAS interventions, attitudes towards collaboration in AMS and the perceived challenges of implementing GPPAS interventions. Systems Engineering Initiative for Patient Safety (SEIPS 2.0) model and factor analyses will guide the structure of GPPAS model through identifying the determinants of GPPAS uptake. The implementable GPPAS strategies will be selected based on empirical feasibility assessment by AMS stakeholders using the APEASE (Affordability, Practicability, Effectiveness and cost-effectiveness, Acceptability, Side-effects and safety, Equity) criteria. Discussion: The GPPAS model might have p

Setting up an interprofessional team for antimicrobial stewardship (AMS) to improve the quality and safety of antimicrobial use in primary care is essential but challenging. This study aimed to investigate the convergent and divergent attitudes and views of general practitioners (GPs) and community pharmacists (CPs) about AMS implementation and their perceived challenges of collaboration to design a GP–pharmacist collaborative AMS (GPPAS) model. Nationwide surveys of GPs and CPs across Australia were conducted January-October 2019. Chi square statistics and a theoretical framework were used for comparative analyses of quantitative and qualitative data, respectively. In total, 999 participants responded to the surveys with 15.4% (n = 386) response rates for GPs and 30.7% (n = 613) for CPs. GPs and CPs were aware about AMS however their interprofessional perceptions varied to the benefits of AMS programs. CPs indicated that they would need AMS training; significantly higher than GPs (GP vs. CP; 46.4% vs. 76.5%; p < 0.0001). GPs’ use of the Therapeutic Guideline Antibiotic was much higher than CPs (83.2% vs. 45.5%; p < 0.0001). No interprofessional difference was found in the very-limited use of patient information leaflets (p < 0.1162) and point-of-care tests (p < 0.7848). While CPs were more willing (p < 0.0001) to collaborate with GPs, both groups were convergent in views that policies that support GP–CP collaboration are needed to implement GPPAS strategies. GP–pharmacist collaborative group meetings (54.9% vs. 82.5%) and antimicrobial audit (46.1% vs. 86.5%) models were inter-professionally supported to optimise antimicrobial therapy, but an attitudinal divergence was significant (p < 0.001). The challenges towards GP–CP collaboration in AMS were identified by both at personal, logistical and organisational environment level. There are opportunities for GP–CP collaboration to improve AMS in Australian p

The National Antimicrobial Prescribing Survey (NAPS) is a web-based qualitative auditing platform that provides a standardized and validated tool to assist hospitals in assessing the appropriateness of antimicrobial prescribing practices. Since its release in 2013, the NAPS has been adopted by all hospital types within Australia, including public and private facilities, and supports them in meeting the national standards for accreditation. Hospitals can generate real-time reports to assist with local antimicrobial stewardship (AMS) activities and interventions. De-identified aggregate data from the NAPS are also submitted to the Antimicrobial Use and Resistance in Australia surveillance system, for national reporting purposes, and to strengthen national AMS strategies. With the successful implementation of the programme within Australia, the NAPS has now been adopted by countries with both well-resourced and resource-limited healthcare systems. We provide here a narrative review describing the experience of users utilizing the NAPS programme in Canada, Malaysia and Bhutan. We highlight the key barriers and facilitators to implementation and demonstrate that the NAPS methodology is feasible, generalizable and translatable to various settings and able to assist in initiatives to optimize the use of antimicrobials.

BACKGROUND: Invasive fungal disease (IFD) is a common and important complication in children with acute myeloid leukaemia (AML). We describe the epidemiology of IFD in a large multicentre cohort of children with AML. METHODS: As part of the retrospective multicentre cohort TERIFIC (The Epidemiology and Risk factors for Invasive Fungal Infections in immunocompromised Children) study, proven/probable/possible IFD episodes occurring in children with primary or relapsed/refractory AML from 2003 to 2014 were analysed. Crude IFD prevalence, clinical characteristics, microbiology and treatment were assessed. Kaplan-Meier survival analysis was used to estimate 6-month survival. RESULTS: There were 66 IFD episodes diagnosed in 63 children with AML. The majority (75.8%) of episodes occurred in the context of primary AML therapy. During primary AML therapy, the overall prevalence was 20.7% (95% CI 15.7%-26.5%) for proven/probable/possible IFD and 10.3% (95% CI 6.7%-15.0%) for proven/probable IFD. Of primary AML patients, 8.2% had IFD diagnosed during the first cycle of chemotherapy. Amongst pathogens implicated in proven/probable IFD episodes, 74.4% were moulds, over a third (37.9%) of which were non-Aspergillus spp. Antifungal prophylaxis preceded 89.4% of IFD episodes, most commonly using fluconazole (50% of IFD episodes). All-cause mortality at 6 months from IFD diagnosis was 16.7% with IFD-related mortality of 7.6% (all in cases of proven IFD). CONCLUSIONS: IFD is a common and serious complication during paediatric AML therapy. Mould infections, including non-Aspergillus spp. predominated in this cohort. A systematic approach to the identification of patients at risk, and a targeted prevention strategy for IFD is needed.

BACKGROUND: The impact febrile neutropenia (FN) has on the health-related quality of life (HRQoL) of children with cancer and their families is poorly understood. We sought to characterize the course of child and parent HRQoL during and following FN episodes. METHOD: Data on HRQoL were collected in the multisite Australian Predicting Infectious ComplicatioNs in Children with Cancer (PICNICC) study. Participants were enrolled between November 2016 to January 2018. The Child Health Utility (CHU9D) was used to assess HRQoL in children (N = 167 FN events) and the Assessment of Quality of Life (AQoL-8D) was used to assess HRQoL parents (N = 218 FN events) at three time points: 0-3 days, 7-days and 30-days following the onset of FN. Group-based trajectory modeling (GBTM) was used to characterize the course of HRQoL. FINDINGS: For children, three distinct groups were identified: persistently low HRQoL over the 30-day course of follow-up (chronic: N = 78/167; 47%), increasing HRQoL after the onset of FN to 30 days follow-up (recovering: N = 36/167; 22%), and persistently high HRQoL at all three timepoints (resilient: N = 53/167; 32%). Applying these definitions, parents were classified into two distinct groups: chronic (N = 107/218, 49%) and resilient (N = 111/218, 51%). The child being male, having solid cancer, the presence of financial stress, and relationship difficulties between the parent and child were significant predictors of chronic group membership for both parents and children. Children classified as high-risk FN were significantly more likely to belong to the recovery group. Being female, having blood cancers and the absence of financial or relationship difficulties were predictive of both parents and children being in the resilient group. INTERPRETATION: Approximately half the children and parents had chronically low HRQoL scores, which did not improve following resolution of the FN episode. The child's sex, cancer type, and presence of financial and relations

Inappropriate antimicrobial prescribing contributes to increasing antimicrobial resistance. An antimicrobial stewardship (AMS) program in the form of quality improvement activities that included audit and feedback, clinical decision support and education was developed to help optimise prescribing in general practice. The aim of this study was to evaluate the implementation of this program (Guidance GP) in three general practices in Melbourne, Australia, between November 2019 and August 2020. Thirty-one general practitioners (GPs) participated in the program, with 11 GPs and three practice managers participating in follow-up focus groups and interviews to explore the acceptability and feasibility of the program. Our findings showed that the quality improvement activities were acceptable to GPs, if they accurately fit GPs' decision-making process and workflow. It was also important that they provided clinically meaningful information in the form of audit and feedback to GPs. The time needed to coordinate the program, and costs to implement the program were some of the potential barriers identified. Facilitators of success were a "whole of practice" approach with enthusiastic GPs and practice staff, and an identified practice champion. The findings of this research will inform implementation strategies for both the Guidance GP program and AMS programs more broadly in Australian general practice, which will be critical for general practice participation and engagement.

Setting up an interprofessional team for antimicrobial stewardship (AMS) to improve the quality and safety of antimicrobial use in primary care is essential but challenging. This study aimed to investigate the convergent and divergent attitudes and views of general practitioners (GPs) and community pharmacists (CPs) about AMS implementation and their perceived challenges of collaboration to design a GP-pharmacist collaborative AMS (GPPAS) model. Nationwide surveys of GPs and CPs across Australia were conducted January-October 2019. Chi square statistics and a theoretical framework were used for comparative analyses of quantitative and qualitative data, respectively. In total, 999 participants responded to the surveys with 15.4% (n = 386) response rates for GPs and 30.7% (n = 613) for CPs. GPs and CPs were aware about AMS however their interprofessional perceptions varied to the benefits of AMS programs. CPs indicated that they would need AMS training; significantly higher than GPs (GP vs. CP; 46.4% vs. 76.5%; p < 0.0001). GPs' use of the Therapeutic Guideline Antibiotic was much higher than CPs (83.2% vs. 45.5%; p < 0.0001). No interprofessional difference was found in the very-limited use of patient information leaflets (p < 0.1162) and point-of-care tests (p < 0.7848). While CPs were more willing (p < 0.0001) to collaborate with GPs, both groups were convergent in views that policies that support GP-CP collaboration are needed to implement GPPAS strategies. GP-pharmacist collaborative group meetings (54.9% vs. 82.5%) and antimicrobial audit (46.1% vs. 86.5%) models were inter-professionally supported to optimise antimicrobial therapy, but an attitudinal divergence was significant (p < 0.001). The challenges towards GP-CP collaboration in AMS were identified by both at personal, logistical and organisational environment level. There are opportunities for GP-CP collaboration to improve AMS in Australian primary care. However, strengthening GP-pharmacy collaborative

BACKGROUND: Rising antimicrobial resistance (AMR) in primary care is a growing concern and a threat to community health. The rise of AMR can be slowed down if general practitioners (GPs) and community pharmacists (CPs) could work as a team to implement antimicrobial stewardship (AMS) programs for optimal use of antimicrobial(s). However, the evidence supporting a GP pharmacist collaborative AMS implementation model (GPPAS) in primary care remains limited. AIM: With an aim to design a GPPAS model in Australia, this paper outlines how this model will be developed. METHODS: This exploratory study undertakes a systematic review, a scoping review, nationwide surveys, and qualitative interviews to design the model. Medical Research Council (MRC) framework and Normalization Process Theory are utilized as guides. Reviews will identify the list of effective GPPAS interventions. Two AMS surveys and paired interviews of GPs and CPs across Australia will explore their convergent and divergent views about the GPPAS interventions, attitudes towards collaboration in AMS and the perceived challenges of implementing GPPAS interventions. Systems Engineering Initiative for Patient Safety (SEIPS 2.0) model and factor analyses will guide the structure of GPPAS model through identifying the determinants of GPPAS uptake. The implementable GPPAS strategies will be selected based on empirical feasibility assessment by AMS stakeholders using the APEASE (Affordability, Practicability, Effectiveness and cost-effectiveness, Acceptability, Side-effects and safety, Equity) criteria. DISCUSSION: The GPPAS model might have potential implications to inform how to better involve GPs and CPs in AMS, and, to improve collaborative services to optimize antimicrobial use and reduce AMR in primary care.

BACKGROUND: Cancer patients are at significant risk of developing sepsis due to underlying malignancy and necessary treatments. Little is known about the economic burden of sepsis in this high-risk population. We estimate the short- and long-term healthcare costs of care of cancer patients with and without sepsis using individual-level linked-administrative data. METHODS: We conducted a population-based matched cohort study of cancer patients aged ≥18, diagnosed between 2010 and 2017. Cases were identified if diagnosed with sepsis during the study period, and were matched 1:1 by age, sex, cancer type and other variables to controls without sepsis. Mean costs (2018 Canadian dollars) for patients with and without sepsis up to 5 years were estimated adjusted using survival probabilities at partitioned intervals. We estimated excess cost associated with sepsis presented as a cost difference between the two cohorts. Haematological and solid cancers were analysed separately. RESULTS: 77,483 cancer patients with sepsis were identified and matched. 64.3% of the cohort were aged ≥65, 46.3% female and 17.8% with haematological malignancies. Among solid tumour patients, the excess cost of care among patients who developed sepsis was $29,081 (95%CI, $28,404-$29,757) in the first year, rising to $60,714 (95%CI, $59,729-$61,698) over 5 years. This was higher for haematology patients; $46,154 (95%CI, $45,505-$46,804) in year 1, increasing to $75,931 (95%CI, $74,895-$76,968). CONCLUSIONS: Sepsis imposes substantial economic burden and can result in a doubling of cancer care costs, particularly during the first year of cancer diagnosis. These estimates are helpful in improving our understanding of burden of sepsis along the cancer pathway and to deploy targeted strategies to alleviate this burden.

Background The impact febrile neutropenia (FN) has on the health-related quality of life (HRQoL) of children with cancer and their families is poorly understood. We sought to characterize the course of child and parent HRQoL during and following FN episodes. Method Data on HRQoL were collected in the multisite Australian Predicting Infectious ComplicatioNs in Children with Cancer (PICNICC) study. Participants were enrolled between November 2016 to January 2018. The Child Health Utility (CHU9D) was used to assess HRQoL in children (N = 167 FN events) and the Assessment of Quality of Life (AQoL-8D) was used to assess HRQoL parents (N = 218 FN events) at three time points: 0–3 days, 7-days and 30-days following the onset of FN. Group-based trajectory modeling (GBTM) was used to characterize the course of HRQoL. Findings For children, three distinct groups were identified: persistently low HRQoL over the 30-day course of follow-up (chronic: N = 78/167; 47%), increasing HRQoL after the onset of FN to 30 days follow-up (recovering: N = 36/167; 22%), and persistently high HRQoL at all three timepoints (resilient: N = 53/167; 32%). Applying these definitions, parents were classified into two distinct groups: chronic (N = 107/218, 49%) and resilient (N = 111/218, 51%). The child being male, having solid cancer, the presence of financial stress, and relationship difficulties between the parent and child were significant predictors of chronic group membership for both parents and children. Children classified as high-risk FN were significantly more likely to belong to the recovery group. Being female, having blood cancers and the absence of financial or relationship difficulties were predictive of both parents and children being in the resilient group. Interpretation Approximately half the children and parents had chronically low HRQoL scores, which did not improve following resolution of the FN episode. The child's sex, cancer type, and presence of financial and relationship

Background The impact febrile neutropenia (FN) has on the health-related quality of life (HRQoL) of children with cancer and their families is poorly understood. We sought to characterize the course of child and parent HRQoL during and following FN episodes. Method Data on HRQoL were collected in the multisite Australian Predicting Infectious ComplicatioNs in Children with Cancer (PICNICC) study. Participants were enrolled between November 2016 to January 2018. The Child Health Utility (CHU9D) was used to assess HRQoL in children (N = 167 FN events) and the Assessment of Quality of Life (AQoL-8D) was used to assess HRQoL parents (N = 218 FN events) at three time points: 0–3 days, 7-days and 30-days following the onset of FN. Group-based trajectory modeling (GBTM) was used to characterize the course of HRQoL. Findings For children, three distinct groups were identified: persistently low HRQoL over the 30-day course of follow-up (chronic: N = 78/167; 47%), increasing HRQoL after the onset of FN to 30 days follow-up (recovering: N = 36/167; 22%), and persistently high HRQoL at all three timepoints (resilient: N = 53/167; 32%). Applying these definitions, parents were classified into two distinct groups: chronic (N = 107/218, 49%) and resilient (N = 111/218, 51%). The child being male, having solid cancer, the presence of financial stress, and relationship difficulties between the parent and child were significant predictors of chronic group membership for both parents and children. Children classified as high-risk FN were significantly more likely to belong to the recovery group. Being female, having blood cancers and the absence of financial or relationship difficulties were predictive of both parents and children being in the resilient group. Interpretation Approximately half the children and parents had chronically low HRQoL scores, which did not improve following resolution of the FN episode. The child's sex, cancer type, and presence of financial and relationship

Background The impact febrile neutropenia (FN) has on the health-related quality of life (HRQoL) of children with cancer and their families is poorly understood. We sought to characterize the course of child and parent HRQoL during and following FN episodes. Method Data on HRQoL were collected in the multisite Australian Predicting Infectious ComplicatioNs in Children with Cancer (PICNICC) study. Participants were enrolled between November 2016 to January 2018. The Child Health Utility (CHU9D) was used to assess HRQoL in children (N = 167 FN events) and the Assessment of Quality of Life (AQoL-8D) was used to assess HRQoL parents (N = 218 FN events) at three time points: 0–3 days, 7-days and 30-days following the onset of FN. Group-based trajectory modeling (GBTM) was used to characterize the course of HRQoL. Findings For children, three distinct groups were identified: persistently low HRQoL over the 30-day course of follow-up (chronic: N = 78/167; 47%), increasing HRQoL after the onset of FN to 30 days follow-up (recovering: N = 36/167; 22%), and persistently high HRQoL at all three timepoints (resilient: N = 53/167; 32%). Applying these definitions, parents were classified into two distinct groups: chronic (N = 107/218, 49%) and resilient (N = 111/218, 51%). The child being male, having solid cancer, the presence of financial stress, and relationship difficulties between the parent and child were significant predictors of chronic group membership for both parents and children. Children classified as high-risk FN were significantly more likely to belong to the recovery group. Being female, having blood cancers and the absence of financial or relationship difficulties were predictive of both parents and children being in the resilient group. Interpretation Approximately half the children and parents had chronically low HRQoL scores, which did not improve following resolution of the FN episode. The child's sex, cancer type, and presence of financial and relationship

Background Penicillin allergies are associated with inferior patient and antimicrobial stewardship outcomes. We implemented a whole-of-hospital program to assess the efficacy of inpatient delabeling for low-risk penicillin allergies in hospitalized inpatients. Methods Patients ≥ 18 years of age with a low-risk penicillin allergy were offered a single-dose oral penicillin challenge or direct label removal based on history (direct delabeling). The primary endpoint was the proportion of patients delabeled. Key secondary endpoints were antibiotic utilization pre- (index admission) and post-delabeling (index admission and 90 days). Results Between 21 January 2019 and 31 August 2019, we assessed 1791 patients reporting 2315 antibiotic allergies, 1225 with a penicillin allergy. Three hundred fifty-five patients were delabeled: 161 by direct delabeling and 194 via oral penicillin challenge. Ninety-seven percent (194/200) of patients were negative upon oral penicillin challenge. In the delabeled patients, we observed an increase in narrow-spectrum penicillin usage (adjusted odds ratio [OR], 10.51 [95% confidence interval {CI}, 5.39–20.48]), improved appropriate antibiotic prescribing (adjusted OR, 2.13 [95% CI, 1.45–3.13]), and a reduction in restricted antibiotic usage (adjusted OR, 0.38 [95% CI, .27–.54]). In the propensity score analysis, there was an increase in narrow-spectrum penicillins (OR, 10.89 [95% CI, 5.09–23.31]) and β-lactam/β-lactamase inhibitors (OR, 6.68 [95% CI, 3.94–11.35]) and a reduction in restricted antibiotic use (OR, 0.52 [95% CI, .36–.74]) and inappropriate prescriptions (relative risk ratio, 0.43 [95% CI, .26–.72]) in the delabeled group compared with the group who retained their allergy label. Conclusions This health services program using a combination of direct delabeling and oral penicillin challenge resulted in significant impacts on the use of preferred antibiotics and appropriate prescribing.

Aminoglycosides are commonly prescribed to children with febrile neutropenia (FN) but their impact on clinical outcomes is uncertain and extent of guideline compliance is unknown. We aimed to review aminoglycoside prescription and additional antibiotic prescribing, guideline compliance and outcomes for children with FN. We analysed data from the Australian Predicting Infectious ComplicatioNs in Children with Cancer (PICNICC) prospective multicentre cohort study, in children <18 years with FN between November 2016 and January 2018. Impact of aminoglycoside use in the first 12 hours of FN on composite unfavourable outcome of death, ICU admission, relapse of infection or late-onset sepsis was assessed using multivariable Cox regression. The study was conducted in Australia where antimicrobial resistance among gram negative organisms is relatively low. Data from 858 episodes of FN in 462 children from 8 centres were assessed, median age 5.8 years (IQR 3.5–10.8 years). Early empiric aminoglycosides were prescribed in 255 episodes (29.7%). Guideline non-compliance was common: in 46% (184/400) of eligible episodes, patients did not receive aminoglycosides, while aminoglycosides were prescribed in 9% (39/ 458) of guideline-ineligible episodes. Adjusted hazard of the composite unfavourable outcome was 3.81 times higher among patients prescribed empiric aminoglycosides than among those who weren’t (95% confidence interval, 1.89–7.67), with no increased risk of unfavourable outcome in eligible patients who did not receive aminoglycosides. In a large paediatric FN cohort, aminoglycoside prescription was common and was often non-compliant with guidelines. There was no evidence for improved outcome with aminoglycosides, even in those who met guideline criteria, within a low-resistance setting. Empiric aminoglycoside prescription for children with FN requires urgent review in guidelines and in national practice.

The pharmacist's role in hospital antimicrobial stewardship (AMS) programs is known to improve patient safety and the quality of care. Despite this, many Australian hospitals struggle to provide adequate pharmacy AMS program resourcing and need to explore newer models of care. The Pharmacy Board of Australia's Guidelines for Dispensing Medicines permit suitably qualified, competent and experienced pharmacy technicians to assist pharmacists in 'tasks in a pharmacy department'. The pharmacy technician workforce is expanding, and there is growing interest in career advancement and expansion of the pharmacy technician role. We propose that the pharmacy technician, a well-integrated member of many Australian hospital pharmacy departments, can play an important role in hospital AMS programs. To bolster AMS initiatives in Australian hospitals, this paper explores the existing evidence for pharmacy technicians in AMS programs and describes how this role may be better supported in Australia.

Implementing antimicrobial stewardship (AMS) programs is central to optimise antimicrobial use in primary care. This study aims to assess general practitioners’ (GPs’) awareness of AMS, uptake of AMS strategies, attitudes towards GP–pharmacist collaboration in AMS and future AMS improvement strategies. A paper-based survey of nationally representative GPs across Australia was conducted in 2019. Of 386 respondent GPs, 68.9% were familiar with AMS. Respondents most frequently used the Therapeutic Guidelines (TG) (83.2%, 321/385) and delayed antimicrobial prescribing (72.2%, 278/385) strategies, whereas few utilised point-of-care tests (18.4%, 71/382), patient information leaflets (20.2%, 78/384), peer prescribing reports (15.5%, 60/384) and audit and feedback (9.8%, 38/384). GPs were receptive to pharmacists’ recommendations on the choice (50.5%, 192/381) and dose (63%, 241/382) of antimicrobials, and more than 60% (235/381) supported a policy fostering increased GP–pharmacist collaboration. Most GPs agreed to have AMS training (72%, 278/386), integration of electronic TG (eTG) with prescribing software (88.3%, 341/386) and policies limiting the prescribing of selected antimicrobials (74.4%, 287/386) in the future. Conclusively, GPs are aware of the importance of judicious antimicrobial prescribing but inadequately uptake evidence-based AMS strategies. The majority of GPs support GP–pharmacist collaborative AMS approaches to optimise antimicrobial use. Developing a feasible GP–pharmacist collaborative AMS implementation model and facilitating stewardship resources and training could foster AMS activities in primary care.

The pharmacist's role in hospital antimicrobial stewardship (AMS) programs is known to improve patient safety and the quality of care. Despite this, many Australian hospitals struggle to provide adequate pharmacy AMS program resourcing and need to explore newer models of care. The Pharmacy Board of Australia's Guidelines for Dispensing Medicines permit suitably qualified, competent and experienced pharmacy technicians to assist pharmacists in 'tasks in a pharmacy department'. The pharmacy technician workforce is expanding, and there is growing interest in career advancement and expansion of the pharmacy technician role. We propose that the pharmacy technician, a well-integrated member of many Australian hospital pharmacy departments, can play an important role in hospital AMS programs. To bolster AMS initiatives in Australian hospitals, this paper explores the existing evidence for pharmacy technicians in AMS programs and describes how this role may be better supported in Australia.

Implementing antimicrobial stewardship (AMS) programs is central to optimise antimicrobial use in primary care. This study aims to assess general practitioners' (GPs') awareness of AMS, uptake of AMS strategies, attitudes towards GP-pharmacist collaboration in AMS and future AMS improvement strategies. A paper-based survey of nationally representative GPs across Australia was conducted in 2019. Of 386 respondent GPs, 68.9% were familiar with AMS. Respondents most frequently used the Therapeutic Guidelines (TG) (83.2%, 321/385) and delayed antimicrobial prescribing (72.2%, 278/385) strategies, whereas few utilised point-of-care tests (18.4%, 71/382), patient information leaflets (20.2%, 78/384), peer prescribing reports (15.5%, 60/384) and audit and feedback (9.8%, 38/384). GPs were receptive to pharmacists' recommendations on the choice (50.5%, 192/381) and dose (63%, 241/382) of antimicrobials, and more than 60% (235/381) supported a policy fostering increased GP-pharmacist collaboration. Most GPs agreed to have AMS training (72%, 278/386), integration of electronic TG (eTG) with prescribing software (88.3%, 341/386) and policies limiting the prescribing of selected antimicrobials (74.4%, 287/386) in the future. Conclusively, GPs are aware of the importance of judicious antimicrobial prescribing but inadequately uptake evidence-based AMS strategies. The majority of GPs support GP-pharmacist collaborative AMS approaches to optimise antimicrobial use. Developing a feasible GP-pharmacist collaborative AMS implementation model and facilitating stewardship resources and training could foster AMS activities in primary care.

Aminoglycosides are commonly prescribed to children with febrile neutropenia (FN) but their impact on clinical outcomes is uncertain and extent of guideline compliance is unknown. We aimed to review aminoglycoside prescription and additional antibiotic prescribing, guideline compliance and outcomes for children with FN. We analysed data from the Australian Predicting Infectious ComplicatioNs in Children with Cancer (PICNICC) prospective multicentre cohort study, in children <18 years with FN between November 2016 and January 2018. Impact of aminoglycoside use in the first 12 hours of FN on composite unfavourable outcome of death, ICU admission, relapse of infection or late-onset sepsis was assessed using multivariable Cox regression. The study was conducted in Australia where antimicrobial resistance among gram negative organisms is relatively low. Data from 858 episodes of FN in 462 children from 8 centres were assessed, median age 5.8 years (IQR 3.5-10.8 years). Early empiric aminoglycosides were prescribed in 255 episodes (29.7%). Guideline non-compliance was common: in 46% (184/400) of eligible episodes, patients did not receive aminoglycosides, while aminoglycosides were prescribed in 9% (39/458) of guideline-ineligible episodes. Adjusted hazard of the composite unfavourable outcome was 3.81 times higher among patients prescribed empiric aminoglycosides than among those who weren't (95% confidence interval, 1.89-7.67), with no increased risk of unfavourable outcome in eligible patients who did not receive aminoglycosides. In a large paediatric FN cohort, aminoglycoside prescription was common and was often non-compliant with guidelines. There was no evidence for improved outcome with aminoglycosides, even in those who met guideline criteria, within a low-resistance setting. Empiric aminoglycoside prescription for children with FN requires urgent review in guidelines and in national practice.

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.

Background Numerous paediatric febrile neutropenia (FN) clinical decision rules (CDRs) have been derived. Validation studies show reduced performance in external settings. We evaluated the association between variables common across published FN CDRs and bacterial infection and recalibrated existing CDRs using these data. Methods Prospective data from the Australian-PICNICC study which enrolled 858 FN episodes in children with cancer were used. Variables shown to be significant predictors of infection or adverse outcome in >1 CDR were analysed using multivariable logistic regression. Recalibration included re-evaluation of beta-coefficients (logistic model) or recursive-partition analysis (tree-based models). Findings Twenty-five unique variables were identified across 17 FN CDRs. Fourteen were included in >1 CDR and 10 were analysed in our dataset. On univariate analysis, location, temperature, hypotension, rigors, severely unwell and decreasing platelets, white cell count, neutrophil count and monocyte count were significantly associated with bacterial infection. On multivariable analysis, decreasing platelets, increasing temperature and the appearance of being clinically unwell remained significantly associated. Five rules were recalibrated. Across all rules, recalibration increased the AUC-ROC and low-risk yield as compared to non-recalibrated data. For the SPOG-adverse event CDR, recalibration also increased sensitivity and specificity and external validation showed reproducibility. Interpretation Degree of marrow suppression (low platelets), features of inflammation (temperature) and clinical judgement (severely unwell) have been consistently shown to predict infection in children with FN. Recalibration of existing CDRs is a novel way to improve diagnostic performance of CDRs and maintain relevance over time.

Background Numerous paediatric febrile neutropenia (FN) clinical decision rules (CDRs) have been derived. Validation studies show reduced performance in external settings. We evaluated the association between variables common across published FN CDRs and bacterial infection and recalibrated existing CDRs using these data. Methods Prospective data from the Australian-PICNICC study which enrolled 858 FN episodes in children with cancer were used. Variables shown to be significant predictors of infection or adverse outcome in >1 CDR were analysed using multivariable logistic regression. Recalibration included re-evaluation of beta-coefficients (logistic model) or recursive-partition analysis (tree-based models). Findings Twenty-five unique variables were identified across 17 FN CDRs. Fourteen were included in >1 CDR and 10 were analysed in our dataset. On univariate analysis, location, temperature, hypotension, rigors, severely unwell and decreasing platelets, white cell count, neutrophil count and monocyte count were significantly associated with bacterial infection. On multivariable analysis, decreasing platelets, increasing temperature and the appearance of being clinically unwell remained significantly associated. Five rules were recalibrated. Across all rules, recalibration increased the AUC-ROC and low-risk yield as compared to non-recalibrated data. For the SPOG-adverse event CDR, recalibration also increased sensitivity and specificity and external validation showed reproducibility. Interpretation Degree of marrow suppression (low platelets), features of inflammation (temperature) and clinical judgement (severely unwell) have been consistently shown to predict infection in children with FN. Recalibration of existing CDRs is a novel way to improve diagnostic performance of CDRs and maintain relevance over time.

Purpose: The aim of this study was to determine if measurement of B cell protective immunity was associated with susceptibility to sinopulmonary infection in kidney transplant recipients. Methods and Materials: A prospective cohort of 168 patients with stable graft function (median 4.1 years) underwent assessment of B-lymphocyte antigen CD19 (CD19+) cell number, immunoglobulin G concentration, and seroresponses to influenza vaccination upon study entry. Patients received a single dose of a trivalent, seasonal influenza vaccine. Result(s): After 2 years follow-up, 31 patients (18%) developed sinopulmonary infection. CD19+ cell number was strongly associated with future sinopulmonary infection. A higher proportion of patients with CD19+ cell counts below the fifth percentile for controls developed sinopulmonary infections than those above the fifth percentile, 30% (23 of 77 patients) compared with 9% (7 of 79 patients; P =.001). There was a trend toward a higher proportion of patients with reduced immunoglobulin G concentrations developing infections than in the normal range for controls, 29% (14 of 48 patients) compared with 15% (16 of 108 patients; P =.060). Influenza vaccination seroresponses were poor in patients and controls such that they could not be used to identify a subgroup of patients at high risk for the development of severe pulmonary infection. Conclusion(s): Monitoring B-cell numbers represents a simple, inexpensive means of stratifying transplant recipients' risk of sinopulmonary infection.Copyright © 2018 Elsevier Inc.

Background: The aim of this study was to determine whether a composite score of simple immune biomarkers and clinical characteristics could predict severe infections in kidney transplant recipients. Method(s): We conducted a prospective study of 168 stable kidney transplant recipients who underwent measurement of lymphocyte subsets, immunoglobulins, and renal function at baseline and were followed up for 2 years for the development of any severe infections, defined as infection requiring hospitalization. A point score was developed to predict severe infection based on logistic regression analysis of factors in baseline testing. Result(s): Fifty-nine (35%) patients developed severe infection, 36 (21%) had two or more severe infections, and 3 (2%) died of infection. A group of 19 (11%) patients had the highest predicted infectious risk (>60%), as predicted by the score. Predictive variables were mycophenolate use, graft function, CD4+, and natural killer cell number. The level of immunosuppression score had an area under the receiver operating curve of 0.75 (95% CI: 0.67-0.83). Conclusion(s): Our level of immunosuppression score for predicting the development of severe infection over 2 years has sufficient prognostic accuracy for identification of high-risk patients. This data can inform research that examines strategies to reduce the risks of infection.Copyright © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Purpose: The aim of this study was to determine if measurement of B cell protective immunity was associated with susceptibility to sinopulmonary infection in kidney transplant recipients. Methods and Materials: A prospective cohort of 168 patients with stable graft function (median 4.1 years) underwent assessment of B-lymphocyte antigen CD19 (CD19+) cell number, immunoglobulin G concentration, and seroresponses to influenza vaccination upon study entry. Patients received a single dose of a trivalent, seasonal influenza vaccine. Result(s): After 2 years follow-up, 31 patients (18%) developed sinopulmonary infection. CD19+ cell number was strongly associated with future sinopulmonary infection. A higher proportion of patients with CD19+ cell counts below the fifth percentile for controls developed sinopulmonary infections than those above the fifth percentile, 30% (23 of 77 patients) compared with 9% (7 of 79 patients; P =.001). There was a trend toward a higher proportion of patients with reduced immunoglobulin G concentrations developing infections than in the normal range for controls, 29% (14 of 48 patients) compared with 15% (16 of 108 patients; P =.060). Influenza vaccination seroresponses were poor in patients and controls such that they could not be used to identify a subgroup of patients at high risk for the development of severe pulmonary infection. Conclusion(s): Monitoring B-cell numbers represents a simple, inexpensive means of stratifying transplant recipients' risk of sinopulmonary infection.Copyright © 2018 Elsevier Inc.

Background: The aim of this study was to determine whether a composite score of simple immune biomarkers and clinical characteristics could predict severe infections in kidney transplant recipients. Method(s): We conducted a prospective study of 168 stable kidney transplant recipients who underwent measurement of lymphocyte subsets, immunoglobulins, and renal function at baseline and were followed up for 2 years for the development of any severe infections, defined as infection requiring hospitalization. A point score was developed to predict severe infection based on logistic regression analysis of factors in baseline testing. Result(s): Fifty-nine (35%) patients developed severe infection, 36 (21%) had two or more severe infections, and 3 (2%) died of infection. A group of 19 (11%) patients had the highest predicted infectious risk (>60%), as predicted by the score. Predictive variables were mycophenolate use, graft function, CD4+, and natural killer cell number. The level of immunosuppression score had an area under the receiver operating curve of 0.75 (95% CI: 0.67-0.83). Conclusion(s): Our level of immunosuppression score for predicting the development of severe infection over 2 years has sufficient prognostic accuracy for identification of high-risk patients. This data can inform research that examines strategies to reduce the risks of infection.Copyright © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

The annual Aged Care National Antimicrobial Prescribing Survey aims to identify local and national prescribing issues and guide antimicrobial stewardship goals. In the 2018 point prevalence survey, medication charts of over 20,000 residents were reviewed from 407 participating facilities across Australia. On the day of the survey, almost 10% of residents were prescribed an antimicrobial. Nearly two-thirds of recently prescribed antimicrobials were for residents who had no documented signs or symptoms of infection. Over a quarter of antimicrobials had been prescribed for longer than six months. Incomplete documentation was a prominent barrier to proper review of antimicrobial therapy, with the indication, review date or stop date not documented for many prescriptions. Recommendations include using appropriate microbiological testing to guide prescribing, following national antimicrobial prescribing guidelines, documenting the indication for the antimicrobial, and its start, stop and review dates, and monitoring and re-evaluating long-term antimicrobial use.Copyright © 2019 NPS MedicineWise.

The aim of this study was to determine if natural killer cell number (CD3-/CD16+/-/CD56+/-) and cytotoxic killing function predicts severity and frequency of infection in kidney transplant recipients. A cohort of 168 kidney transplant recipients with stable graft function underwent assessment of natural killer cell number and functional killing capacity immediately prior to entry into this prospective study. Participants were followed for 2 years for development of severe infection, defined as hospitalization for infection. Area under receiver operating characteristic (AUROC) curves were used to evaluate the accuracy of natural killer cell number and function for predicting severe infection. Adjusted odds ratios were determined by logistic regression. Fifty-nine kidney transplant recipients (35%) developed severe infection and 7 (4%) died. Natural killer cell function was a better predictor of severe infection than natural killer cell number: AUROC 0.84 and 0.75, respectively (P =.018). Logistic regression demonstrated that after adjustment for age, transplant function, transplant duration, mycophenolate use, and increasing natural killer function (odds ratio [OR] 0.82, 95% confidence interval [CI] 0.74-0.90; P <.0001) but not natural killer number (OR 0.96, 95% CI 0.93-1.00; P =.051) remained significantly associated with a reduced likelihood of severe infection. Natural killer cell function predicts severe infection in kidney transplant recipients.Copyright © 2018 The American Society of Transplantation and the American Society of Transplant Surgeons

BACKGROUND: Surgical antimicrobial prophylaxis (SAP) is a leading indication for antibiotic use in the hospital setting, with demonstrated high rates of inappropriateness. Decision-making for SAP is complex and multifactorial. A greater understanding of these factors is needed to inform the design of targeted antimicrobial stewardship interventions and strategies to support the optimization of SAP and its impacts on patient care. METHODS: A qualitative case study exploring the phenomenon of SAP decision-making. Focus groups were conducted with surgeons, anaesthetists, theatre nurses and pharmacists across one private and two public hospitals in Australia. Thematic analysis was guided by the Theoretical Domains Framework (TDF) and the Capabilities, Opportunities, Motivators-Behaviour (COM-B) model. RESULTS: Fourteen focus groups and one paired interview were completed. Ten of the fourteen TDF domains were identified as relevant. Thematic analysis revealed six significant themes mapped to the COM-B model, and subthemes mapped to the relevant TDF domains in a combined framework. Key themes identified were: 1) Low priority for surgical antimicrobial prophylaxis prescribing skills; 2) Prescriber autonomy takes precedence over guideline compliance; 3) Social codes of prescribing reinforce established practices; 4) Need for improved communication, documentation and collection of data for action; 5) Fears and perceptions of risk hinder appropriate SAP prescribing; and 6) Lack of clarity regarding roles and accountability. CONCLUSIONS: SAP prescribing is a complex process that involves multiple professions across the pre-, intra- and post-operative surgical settings. The utilisation of behaviour change frameworks to identify barriers and enablers to optimal SAP prescribing supports future development of theory-informed antimicrobial stewardship interventions. Interventions should aim to increase surgeon engagement, enhance the prioritisation of and accountability for SAP, an

The aim of this study was to determine if natural killer cell number (CD3- /CD16± /CD56± ) and cytotoxic killing function predicts severity and frequency of infection in kidney transplant recipients. A cohort of 168 kidney transplant recipients with stable graft function underwent assessment of natural killer cell number and functional killing capacity immediately prior to entry into this prospective study. Participants were followed for 2 years for development of severe infection, defined as hospitalization for infection. Area under receiver operating characteristic (AUROC) curves were used to evaluate the accuracy of natural killer cell number and function for predicting severe infection. Adjusted odds ratios were determined by logistic regression. Fifty-nine kidney transplant recipients (35%) developed severe infection and 7 (4%) died. Natural killer cell function was a better predictor of severe infection than natural killer cell number: AUROC 0.84 and 0.75, respectively (P = .018). Logistic regression demonstrated that after adjustment for age, transplant function, transplant duration, mycophenolate use, and increasing natural killer function (odds ratio [OR] 0.82, 95% confidence interval [CI] 0.74-0.90; P < .0001) but not natural killer number (OR 0.96, 95% CI 0.93-1.00; P = .051) remained significantly associated with a reduced likelihood of severe infection. Natural killer cell function predicts severe infection in kidney transplant recipients.

The annual Aged Care National Antimicrobial Prescribing Survey aims to identify local and national prescribing issues and guide antimicrobial stewardship goals In the 2018 point prevalence survey, medication charts of over 20,000 residents were reviewed from 407 participating facilities across Australia On the day of the survey, almost 10% of residents were prescribed an antimicrobial Nearly two-thirds of recently prescribed antimicrobials were for residents who had no documented signs or symptoms of infection Over a quarter of antimicrobials had been prescribed for longer than six months Incomplete documentation was a prominent barrier to proper review of antimicrobial therapy, with the indication, review date or stop date not documented for many prescriptions Recommendations include using appropriate microbiological testing to guide prescribing, following national antimicrobial prescribing guidelines, documenting the indication for the antimicrobial, and its start, stop and review dates, and monitoring and re-evaluating long-term antimicrobial use

OBJECTIVE: This study aimed to explore how general practitioners (GPs) access and use both guidelines and electronic medical records (EMRs) to assist in clinical decision-making when prescribing antibiotics in Australia. DESIGN: This is an exploratory qualitative study with thematic analysis interpreted using the Theory of Planned Behaviour (TPB) framework. SETTING: This study was conducted in general practice in Victoria, Australia. PARTICIPANTS: Twenty-six GPs from five general practices were recruited to participate in five focus groups between February and April 2018. RESULTS: GPs expressed that current EMR systems do not provide clinical decision support to assist with antibiotic prescribing. Access and use of guidelines were variable. GPs who had more clinical experience were less likely to access guidelines than younger and less experienced GPs. Guideline use and guideline-concordant prescribing was facilitated if there was a practice culture encouraging evidence-based practice. However, a lack of access to guidelines and perceived patients' expectation and demand for antibiotics were barriers to guideline-concordant prescribing. Furthermore, guidelines that were easy to access and navigate, free, embedded within EMRs and fit into the clinical workflow were seen as likely to enhance guideline use. CONCLUSIONS: Current barriers to the use of antibiotic guidelines include GPs' experience, patient factors, practice culture, and ease of access and cost of guidelines. To reduce inappropriate antibiotic prescribing and to promote more rational use of antibiotic in the community, guidelines should be made available, accessible and easy to use, with minimal cost to practicing GPs. Integration of evidence-based antibiotic guidelines within the EMR in the form of a clinical decision support tool could optimise guideline use and increase guideline-concordant prescribing.