Antimicrobial use and appropriateness in neutropenic fever: a study of the Hospital National Antimicrobial Prescribing Survey data.

BACKGROUND: Neutropenic fever (NF) is a common complication in patients receiving chemotherapy. Judicious antimicrobial use is paramount to minimize morbidity and mortality and to avoid antimicrobial-related harms. OBJECTIVES: To use an Australian national dataset of antimicrobial prescriptions for the treatment of NF to describe antimicrobial use, prescription guideline compliance and appropriateness; and to compare these findings across different healthcare settings and patient demographics. We also aimed to identify trends and practice changes over time. METHODS: Data were extracted from the Hospital National Antimicrobial Prescribing Survey (Hospital NAPS) database from August 2013 to May 2022. Antimicrobial prescriptions with a NF indication were analysed for antimicrobial use, guideline compliance and appropriateness according to the Hospital NAPS methodology. Demographic factors, hospital classifications and disease characteristics were compared. RESULTS: A total of 2887 (n = 2441 adults, n = 441 paediatric) NF prescriptions from 254 health facilities were included. Piperacillin-tazobactam was the most prescribed antimicrobial. Overall, 87.4% of prescriptions were appropriate. Piperacillin-tazobactam and cefepime had the highest appropriateness though incorrect piperacillin-tazobactam dosing was observed. Lower appropriateness was identified for meropenem, vancomycin, and gentamicin prescribing particularly in the private hospital and paediatric cohorts. The most common reasons for inappropriate prescribing were spectrum too broad, incorrect dosing or frequency, and incorrect duration. CONCLUSIONS: This study provides insights into antimicrobial prescribing practices for NF in Australia. We have identified three key areas for improvement: piperacillin-tazobactam dosing, paediatric NF prescribing and private hospital NF prescribing. Findings from this study will inform the updated Australian and New Zealand consensus guidelines for the management of neutropenic fever in patients with cancer.

Evaluating the cost-effectiveness of [18F]FDG-PET/CT for investigation of persistent or recurrent neutropenic fever in high-risk haematology patients.

BACKGROUND: A recent randomised trial demonstrated [18F]fluorodeoxyglucose positron-emission tomography in combination with low-dose CT (FDG-PET/CT), compared to standard of care computed tomography (CT) imaging, positively impacted antimicrobial management and outcomes of acute leukaemia and haematopoietic stem cell transplant recipients with persistent and recurrent neutropenic fever. We conducted an economic evaluation from a healthcare perspective alongside the clinical trial. METHODS: Unit costs in Australian dollars were applied to all resources used (antimicrobials, diagnostic tests, ICU and hospital bed days). Effectiveness was measured as number of patients with antimicrobial rationalisation, 6-month mortality and quality-adjusted life years (QALYs) derived from patient-reported trial-based health-related quality-of-life. Generalised linear models were used to analyse costs and outcomes. Incremental cost-effectiveness ratios (ICERs) for all outcomes and net monetary benefit (NMB) for QALYs were calculated. We performed bootstrapping with 1000 replications using the recycled predictions method. RESULTS: The adjusted healthcare costs were lower for FDG-PET/CT (mean $49,563; 95%CI 36,867, 65,133) compared to CT (mean $57,574; 95% CI 44,837, 73,347). The difference in QALYs between the two groups was small (0.001; 95% CI -0.001, 0.004). When simulated 1000 times, FDG-PET/CT was the dominant strategy as it was cheaper with better outcomes than the standard CT group in 74% of simulations. The estimated NMBs at willingness-to-pay thresholds of $50,000 and $100,000 per QALY were positive, thus FDG-PET/CT remained cost-effective at these thresholds. CONCLUSIONS: FDG-PET/CT is cost effective when compared to CT for investigation of persistent/recurrent neutropenic fever in high-risk patients, providing further support for incorporation of FDG-PET/CT into clinical guidelines and funding. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov, NCT03429387.

Evolution of Humoral and Cellular Immunity Post-Breakthrough Coronavirus Disease 2019 in Vaccinated Patients With Hematologic Malignancy Receiving Tixagevimab-Cilgavimab.

Background: In-depth immunogenicity studies of tixagevimab-cilgavimab (T-C) are lacking, including following breakthrough coronavirus disease 2019 (COVID-19) in vaccinated patients with hematologic malignancy (HM) receiving T-C as pre-exposure prophylaxis. Methods: We performed a prospective, observational cohort study and detailed immunological analyses of 93 patients with HM who received T-C from May 2022, with and without breakthrough infection, during a follow-up period of 6 months and dominant Omicron BA.5 variant. Results: In 93 patients who received T-C, there was an increase in Omicron BA.4/5 receptor-binding domain (RBD) immunoglobulin G (IgG) antibody titers that persisted for 6 months and was equivalent to 3-dose-vaccinated uninfected healthy controls at 1 month postinjection. Omicron BA.4/5 neutralizing antibody was lower in patients receiving B-cell-depleting therapy within 12 months despite receipt of T-C. COVID-19 vaccination during T-C treatment did not incrementally improve RBD or neutralizing antibody levels. In 16 patients with predominantly mild breakthrough infection, no change in serum neutralization of Omicron BA.4/5 postinfection was detected. Activation-induced marker assay revealed an increase in CD4+ (but not CD8+) T cells post infection, comparable to previously infected healthy controls. Conclusions: Our study provides proof-of-principle for a pre-exposure prophylaxis strategy and highlights the importance of humoral and cellular immunity post-breakthrough COVID-19 in vaccinated patients with HM.

COVID-19 infection among patients with cancer in Australia from 2020 to 2022: a national multicentre cohort study.

Background: The global COVID-19 pandemic disproportionately affected certain populations and its management differed between countries. This national study describes characteristics and outcomes of COVID-19 in patients with cancer in Australia. Methods: We performed a multicentre cohort study of patients with cancer and COVID-19 from March 2020 to April 2022. Data were analysed to determine varying characteristics between cancer types and changes in outcomes over time. Multivariable analysis was performed to determine risk factors associated with oxygen requirement. Findings: 620 patients with cancer from 15 hospitals had confirmed COVID-19. There were 314/620 (50.6%) male patients, median age 63.5 years (IQR 50-72) and majority had solid organ tumours (392/620, 63.2%). The rate of COVID-19 vaccination (≥1 dose) was 73.4% (455/620). Time from symptom onset to diagnosis was median 1 day (IQR 0-3), patients with haematological malignancy had a longer duration of test positivity. Over the study period, there was a significant decline in COVID-19 severity. Risk factors associated with oxygen requirement included male sex (OR 2.34, 95% CI 1.30-4.20, p = 0.004), age (OR 1.03, 95% CI 1.01-1.06, p = 0.005); not receiving early outpatient therapy (OR 2.78, 95% CI 1.41-5.50, p = 0.003). Diagnosis during the omicron wave was associated with lower odds of oxygen requirement (OR 0.24, 95% CI 0.13-0.43, p < 0.0001). Interpretation: Outcomes from COVID-19 in patients with cancer in Australia over the pandemic have improved, potentially related to changing viral strain and outpatient therapies. Funding: This study was supported by research funding from MSD.

Predicting infections in patients with haematological malignancies treated with chimeric antigen receptor T-cell therapies: A systematic scoping review and narrative synthesis.

BACKGROUND: Chimeric antigen receptor T cells (CAR-T cells) are increasingly used to treat haematological malignancies. Strategies for preventing infections in CAR-T-treated patients rely on expert opinions and consensus guidelines. OBJECTIVES: This scoping review aimed to identify risk factors for infections in CAR-T-treated patients with haematological malignancies. DATA SOURCES: A literature search utilized MEDLINE, EMBASE and Cochrane to identify relevant studies from conception until 30 September 2022. STUDY ELIGIBILITY CRITERIA: Trials and observational studies were eligible. PARTICIPANTS: Studies required ≥10 patients treated for haematological malignancy to report infection events (as defined by the study), and either (a) a descriptive, univariate or multivariate analysis of the relationship between infections event and a risk factors for infections, or (b) diagnostic performance of a biochemical/immunological marker in CAR-T-treated patients with infection. METHODS: A scoping review was conducted in accordance with PRISMA guidelines. DATA SOURCES: A literature search utilised MEDLINE, EMBASE and Cochrane to identify relevant studies from conception until September 30, 2022. Eligibility/Participants/Intervention: Trials and observational studies were eligible. Studies required ≥ 10 patients treated for haematological malignancy, to report infection events (as defined by the study), and either A) a descriptive, univariate or multivariate analysis of the relationship between infections event and a risk-factors for infections, or B) diagnostic performance of a biochemical/immunological marker in CAR-T treated patients with infection. ASSESSMENT OF RISK OF BIAS: Bias assessment was undertaken according to Joanna Brigg's Institute criteria for observational studies. METHODS OF DATA SYNTHESIS: Data were synthesized descriptively because of the heterogeneity of reporting. RESULTS: A total of 1522 patients across 15 studies were identified. All-cause infections across haematological malignancies were associated with lines of prior therapy, steroid administration, immune-effector cell-associated neurotoxicity and treatment-emergent neutropenia. Procalcitonin, C-reactive protein and cytokine profiles did not reliably predict infections. Predictors of viral, bacterial and fungal infections were poorly canvassed. DISCUSSION: Meta-analysis of the current literature is not possible because of significant heterogeneity in definitions of infections and risk factors, and small, underpowered cohort studies. Radical revision of how we approach reporting infections for novel therapies is required to promptly identify infection signals and associated risks in patients receiving novel therapies. Prior therapies, neutropenia, steroid administration and immune-effector cell-associated neurotoxicity remain the most associated with infections in CAR-T-treated patients.

Detecting evidence of invasive fungal infections in cytology and histopathology reports enriched with concept-level annotations.

Invasive fungal infections (IFIs) are particularly dangerous to high-risk patients with haematological malignancies and are responsible for excessive mortality and delays in cancer therapy. Surveillance of IFI in clinical settings offers an opportunity to identify potential risk factors and evaluate new therapeutic strategies. However, manual surveillance is both time- and resource-intensive. As part of a broader project aimed to develop a system for automated IFI surveillance by leveraging electronic medical records, we present our approach to detecting evidence of IFI in the key diagnostic domain of histopathology. Using natural language processing (NLP), we analysed cytology and histopathology reports to identify IFI-positive reports. We compared a conventional bag-of-words classification model to a method that relies on concept-level annotations. Although the investment to prepare data supporting concept annotations is substantial, extracting targeted information specific to IFI as a pre-processing step increased the performance of the classifier from the PR AUC of 0.84 to 0.92 and enabled model interpretability. We have made publicly available the annotated dataset of 283 reports, the Cytology and Histopathology IFI Reports corpus (CHIFIR), to allow the clinical NLP research community to further build on our results.

Blood transcriptomics identifies immune signatures indicative of infectious complications in childhood cancer patients with febrile neutropenia.

Objectives: Febrile neutropenia (FN) is a major cause of treatment disruption and unplanned hospitalization in childhood cancer patients. This study investigated the transcriptome of peripheral blood mononuclear cells (PBMCs) in children with cancer and FN to identify potential predictors of serious infection. Methods: Whole-genome transcriptional profiling was conducted on PBMCs collected during episodes of FN in children with cancer at presentation to the hospital (Day 1; n = 73) and within 8-24 h (Day 2; n = 28) after admission. Differentially expressed genes as well as gene pathways that correlated with clinical outcomes were defined for different infectious outcomes. Results: Global differences in gene expression associated with specific immune responses in children with FN and documented infection, compared to episodes without documented infection, were identified at admission. These differences resolved over the subsequent 8-24 h. Distinct gene signatures specific for bacteraemia were identified both at admission and on Day 2. Differences in gene signatures between episodes with bacteraemia and episodes with bacterial infection, viral infection and clinically defined infection were also observed. Only subtle differences in gene expression profiles between non-bloodstream bacterial and viral infections were identified. Conclusion: Blood transcriptome immune profiling analysis during FN episodes may inform monitoring and aid in defining adequate treatment for different infectious aetiologies in children with cancer.

Prevalence and predictors of poor outcome in children with febrile neutropaenia presenting to the emergency department.

OBJECTIVE: Children with acquired neutropaenia due to cancer chemotherapy are at high risk of severe infection. The present study aims to describe the prevalence and predictors of poor outcomes in children with febrile neutropaenia (FN). METHODS: This is a multicentre, prospective observational study in tertiary Australian EDs. Cancer patients with FN were included. Fever was defined as a single temperature ≥38°C, and neutropaenia was defined as an absolute neutrophil count <1000/mm3 . The primary outcome was the ICU admission for organ support therapy (inotropic support, mechanical ventilation, renal replacement therapy, extracorporeal life support). Secondary outcomes were: ICU admission, ICU length of stay (LOS) ≥3 days, proven or probable bacterial infection, hospital LOS ≥7 days and 28-day mortality. Initial vital signs, biomarkers (including lactate) and clinical sepsis scores, including Systemic Inflammatory Response Syndrome, quick Sequential Organ Failure Assessment and quick Paediatric Logistic Organ Dysfunction-2 were evaluated as predictors of poor outcomes. RESULTS: Between December 2016 and January 2018, 2124 episodes of fever in children with cancer were screened, 547 episodes in 334 children met inclusion criteria. Four episodes resulted in ICU admission for organ support therapy, nine episodes required ICU admission, ICU LOS was ≥3 days in four, hospital LOS was ≥7 days in 153 and two patients died within 28 days. Vital signs, blood tests and clinical sepsis scores, including Systemic Inflammatory Response Syndrome, quick Sequential Organ Failure Assessment and quick Paediatric Logistic Organ Dysfunction-2, performed poorly as predictors of these outcomes (area under the receiver operating characteristic curve <0.6). CONCLUSIONS: Very few patients with FN required ICU-level care. Vital signs, biomarkers and clinical sepsis scores for the prediction of poor outcomes are of limited utility in children with FN.

Antifungal use in children with acute leukaemia: state of current evidence and directions for future research.

Invasive fungal disease (IFD) remains a common and serious complication in children treated for leukaemia. Antifungal prescription in children with leukaemia presents unique challenges, particularly due to variation in IFD risk between and within leukaemia treatment protocols, drug toxicities and interactions between antifungals and chemotherapeutic agents. With recent advances in the understanding of IFD epidemiology and large clinical trials in adults assessing antifungals for IFD treatment and prophylaxis, together with paediatric clinical and pharmacokinetic studies, there is a growing body of data to inform optimal antifungal use in children. A panel of infectious diseases and haematology-oncology clinicians with expertise in IFD management compiled a list of 10 key clinical questions following development of the 2021 Australia and New Zealand Mycology Antifungal Consensus Guidelines. A focused literature review was conducted to explore available evidence and identify gaps in knowledge to direct future research. With the changing epidemiology of IFD globally, the ongoing evolution of paediatric leukaemia treatment and the increasing availability of novel antifungal agents, advocacy for paediatric clinical studies will remain vital to optimize IFD prevention and treatment in children with leukaemia.

Cytomegalovirus DNAemia and disease: current-era epidemiology, clinical characteristics and outcomes in cancer patients other than allogeneic haemopoietic transplantation.

BACKGROUND: High-intensity chemotherapy and advances in novel immunotherapies have seen the emergence of cytomegalovirus (CMV) infections in cancer patients other than allogeneic haemopoietic cell transplantation (HCT). Aim To evaluate the epidemiology, clinical characteristics and outcomes of CMV infection in this population. METHODS: A retrospective review of cancer patients other than allogeneic HCT who had CMV DNAemia and/or disease from July 2013 till May 2020 at a quaternary cancer centre was performed. RESULTS: Of 11 485 cancer patients who underwent treatment during this period, 953 patients had CMV DNA testing performed and 238 of them had CMV DNAemia. After excluding patients with allogeneic HCT, 62 patients with CMV DNAemia were identified, of whom 10 had concurrent CMV disease. The most frequent underlying malignancies were B-cell lymphoproliferative disease (LPD) (31%; 19/62), T-cell LPD (21%; 13/62), chronic lymphocytic leukaemia (11%; 7/62) and multiple myeloma (10%; 6/62). Most patients had lymphopenia (77%; 48/62), multiple cancer therapies (63%; 39/62 received ≥2 previous therapies), co-infection (56%; 35/62 had ≥1 co-infection) and corticosteroid therapy (48%; 30/62) within 1 month before CMV diagnosis. CMV DNAemia and disease were observed in patients receiving novel immunotherapies, including bispecific antibody therapy, chimeric-antigen receptor T-cell therapy and immune checkpoint inhibitors. CONCLUSION: Patients with haematological malignancy, particularly B-cell LPD, T-cell LPD, chronic lymphocytic leukaemia and multiple myeloma, were frequently identified to have CMV DNAemia and disease. Lymphopenia, multiple cancer therapies, co-infection and recent receipt of systemic corticosteroids were also commonly observed. Future studies are necessary to determine optimal identification and management of CMV in these patients.

Cost-effectiveness of home-based care of febrile neutropenia in children with cancer.

INTRODUCTION: Home-based treatment of febrile neutropenia (FN) in children with cancer with oral or intravenous antibiotics is safe and effective. There are limited data on the economic impact of this model of care. We evaluated the cost-effectiveness of implementing an FN programme, incorporating home-based intravenous antibiotics for carefully selected patients, in a tertiary paediatric hospital. METHODS: A decision analytic model was constructed to compare costs and outcomes of the home-based FN programme, with usual in-hospital treatment with intravenous antibiotics. The programme included a clinical decision rule to stratify patients by risk for severe infection and home-based eligibility criteria using disease, chemotherapy and patient-level factors. Health outcomes (quality of life) and probabilities of FN risk classification and home-based eligibility were based on prospectively collected data between 2017 and 2019. Patient-level costs were extracted from hospital administrative records. Cost-effectiveness was expressed as the incremental cost per quality-adjusted life year (QALY). FINDINGS: The mean health care cost of home-based FN treatment in low-risk patients was Australian dollars (A$) 7765 per patient compared to A$20,396 for in-hospital treatment (mean difference A$12,632 [95% CI: 12,496-12,767]). Overall, the home-based FN programme was the dominant strategy, being more effective (0.0011 QALY [95% CI: 0.0011-0.0012]) and less costly. Results of the model were most sensitive to proportion of children eligible for home-based care programme. CONCLUSION: Compared to in-hospital FN care, the home-based FN programme is cost-effective, with savings arising from cheaper cost of caring for children at home. These savings could increase as more patients eligible for home-based care are included in the programme.

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.

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.

Consensus guidelines for antifungal stewardship, surveillance and infection prevention, 2021.

Invasive fungal diseases (IFD) are serious infections associated with high mortality, particularly in immunocompromised patients. The prescribing of antifungal agents to prevent and treat IFD is associated with substantial economic burden on the health system, high rates of adverse drug reactions, significant drug-drug interactions and the emergence of antifungal resistance. As the population at risk of IFD continues to grow due to the increased burden of cancer and related factors, the need for hospitals to employ antifungal stewardship (AFS) programmes and measures to monitor and prevent infection has become increasingly important. These guidelines outline the essential components, key interventions and metrics, which can help guide implementation of an AFS programme in order to optimise antifungal prescribing and IFD management. Specific recommendations are provided for quality processes for the prevention of IFD in the setting of outbreaks, during hospital building works, and in the context of Candida auris infection. Recommendations are detailed for the implementation of IFD surveillance to enhance detection of outbreaks, evaluate infection prevention and prophylaxis interventions and to allow benchmarking between hospitals. Areas in which information is still lacking and further research is required are also highlighted.

Antimicrobial stewardship in Australia: the role of qualitative research in programme development.

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.

Antifungal prescribing in neonates: Using national point prevalence survey data from Australia.

We describe contemporary antifungal use in neonates, with point-prevalence survey data from the National Antimicrobial Prescribing Survey across Australian hospitals from 2014 to 2018. There were 247 antifungal prescriptions in 243 neonates in 20 hospitals, median age six days (range 0-27 days). In 219/247 prescriptions (89%) antifungals were prescribed as prophylaxis. Topical (oral) nystatin was the most frequently prescribed in 233/247 prescriptions (94%), followed by fluconazole 11/227 (4%), with substantial variation in dosing for both. Two of 243 neonates (0.8%) had invasive fungal infection. Nystatin use dominates current antifungal prescribing for Australian neonates, in contrast to other countries, and invasive fungal infection is rare. LAY SUMMARY: Novel nationwide surveillance found newborn infants in Australian hospitals commonly receive antifungal medications, mostly oral nystatin. This is given mainly to prevent rather than treat infection, which is rare. There is substantial unexplained variation in dosing of antifungal drugs nationally.

Procalcitonin and Interleukin-10 May Assist in Early Prediction of Bacteraemia in Children With Cancer and Febrile Neutropenia.

Objectives: Febrile neutropenia (FN) causes treatment disruption and unplanned hospitalization in children with cancer. Serum biomarkers are infrequently used to stratify these patients into high or low risk for serious infection. This study investigated plasma abundance of cytokines in children with FN and their ability to predict bacteraemia. Methods: Thirty-three plasma cytokines, C-reactive protein (CRP) and procalcitonin (PCT) were measured using ELISA assays in samples taken at FN presentation (n = 79) and within 8-24 h (Day 2; n = 31). Optimal thresholds for prediction of bacteraemia were identified and the predictive ability of biomarkers in addition to routinely available clinical variables was assessed. Results: The median age of included FN episodes was 6.0 years and eight (10%) had a bacteraemia. On presentation, elevated PCT, IL-10 and Mip1-beta were significantly associated with bacteraemia, while CRP, IL-6 and IL-8 were not. The combination of PCT (≥0.425 ng/ml) and IL-10 (≥4.37 pg/ml) had a sensitivity of 100% (95% CI 68.8-100%) and specificity of 89% (95% CI 80.0-95.0%) for prediction of bacteraemia, correctly identifying all eight bacteraemia episodes and classifying 16 FN episodes as high-risk. There was limited additive benefit of incorporating clinical variables to this model. On Day 2, there was an 11-fold increase in PCT in episodes with a bacteraemia which was significantly higher than that observed in the non-bacteraemia episodes. Conclusion: Elevated PCT and IL-10 accurately identified all bacteraemia episodes in our FN cohort and may enhance the early risk stratification process in this population. Prospective validation and implementation is required to determine the impact on health service utilisation.

Improving intravenous-to-oral antibiotic switch in children: a team-based audit and implementation approach.

Children in hospital are frequently prescribed intravenous antibiotics for longer than needed. Programmes to optimise timely intravenous-to-oral antibiotic switch may limit excessive in-hospital antibiotic use, minimise complications of intravenous therapy and allow children to go home faster. Here, we describe a quality improvement approach to implement a guideline, with team-based education, audit and feedback, for timely, safe switch from intravenous-to-oral antibiotics in hospitalised children. Eligibility for switch was based on evidence-based guidelines and supported by education and feedback. The project was conducted over 12 months in a tertiary paediatric hospital. Primary outcomes assessed were the proportion of eligible children admitted under paediatric and surgical teams switched within 24 hours, and switch timing prior to and after guideline launch. Secondary outcomes were hospital length of stay, recommencement of intravenous therapy or readmission. The percentage of children switched within 24 hours of eligibility significantly increased from 32/50 (64%) at baseline to 203/249 (82%) post-implementation (p=0.006). The median time to switch fell from 15 hours 42 min to 4 hours 20 min (p=0.0006). In addition, there was a 14-hour median reduction in hospital length of stay (p=0.008). Readmission to hospital and recommencement of intravenous therapy did not significantly change postimplementation. This education, audit and feedback approach improved timely intravenous-to-oral switch in children and also allowed for more timely discharge from hospital. The study demonstrates proof of concept for this implementation with a methodology that can be readily adapted to other paediatric inpatient settings.

Managing low-risk febrile neutropenia in children in the time of COVID-19: What matters to parents and clinicians.

AIM: The Australian 'There is no place like home' project is implementing a paediatric low-risk febrile neutropenia (FN) programme across eight paediatric hospitals. We sought to identify the impact of the coronavirus disease 2019 (COVID-19) pandemic on programme implementation. METHODS: Paediatric oncology, infectious diseases and emergency medicine health-care workers and parent/carers were surveyed to explore the impact of the COVID-19 pandemic on home-based FN care. Online surveys were distributed nationally to health-care workers involved in care of children with FN and to parents or carers of children with cancer. RESULTS: Surveys were completed by 78 health-care workers and 32 parents/carers. Overall, 95% of health-care workers had confidence in the safety of home-based FN care, with 35% reporting changes at their own hospitals in response to the pandemic that made them more comfortable with this model. Compared to pre-pandemic, >50% of parent/carers were now more worried about attending the hospital with their child and >80% were interested in receiving home-based FN care. Among both groups, increased telehealth access and acceptance of home-based care, improved patient quality of life and reduced risk of nosocomial infection were identified as programme enablers, while re-direction of resources due to COVID-19 and challenges in implementing change during a crisis were potential barriers. CONCLUSION: There is strong clinician and parent/carer support for home-based management of low-risk FN across Australia. Changes made to the delivery of cancer care in response to the pandemic have generally increased acceptance for home-based treatments and opportunities exist to leverage these to refine the low-risk FN programme.

Quality of inpatient antimicrobial use in hematology and oncology patients.

OBJECTIVES: To compare antimicrobial prescribing practices in Australian hematology and oncology patients to noncancer acute inpatients and to identify targets for stewardship interventions. DESIGN: Retrospective comparative analysis of a national prospectively collected database. METHODS: Using data from the 2014-2018 annual Australian point-prevalence surveys of antimicrobial prescribing in hospitalized patients (ie, Hospital National Antimicrobial Prescribing Survey called Hospital NAPS), the most frequently used antimicrobials, their appropriateness, and guideline concordance were compared among hematology/bone marrow transplant (hemBMT), oncology, and noncancer inpatients in the setting of treatment of neutropenic fever and antibacterial and antifungal prophylaxis. RESULTS: In 454 facilities, 94,226 antibiotic prescriptions for 62,607 adult inpatients (2,230 hemBMT, 1,824 oncology, and 58,553 noncancer) were analyzed. Appropriateness was high for neutropenic fever management across groups (83.4%-90.4%); however, hemBMT patients had high rates of carbapenem use (111 of 746 prescriptions, 14.9%), and 20.2% of these prescriptions were deemed inappropriate. Logistic regression demonstrated that hemBMT patients were more likely to receive appropriate antifungal prophylaxis compared to oncology and noncancer patients (adjusted OR, 5.3; P < .001 for hemBMT compared to noncancer patients). Oncology had a low rate of antifungal prophylaxis guideline compliance (67.2%), and incorrect dosage and frequency were key factors. Compared to oncology patients, hemBMT patients were more likely to receive appropriate nonsurgical antibacterial prophylaxis (aOR, 8.4; 95% CI, 5.3-13.3; P < .001). HemBMT patients were also more likely to receive appropriate nonsurgical antibacterial prophylaxis compared to noncancer patients (OR, 3.1; 95% CI, 1.9-5.0; P < .001). However, in the Australian context, the hemBMT group had higher than expected use of fluoroquinolone prophylaxis (66 of 831 prescriptions, 8%). CONCLUSIONS: This study demonstrates why separate analysis of hemBMT and oncology populations is necessary to identify specific opportunities for quality improvement in each patient group.