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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.

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

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.

Immunocompromised hematology patients are vulnerable to severe COVID-19 and respond poorly to vaccination. Relative deficits in immunity are, however, unclear, especially after 3 vaccine doses. We evaluated immune responses in hematology patients across three COVID-19 vaccination doses. Seropositivity was low after a first dose of BNT162b2 and ChAdOx1 (∼26%), increased to 59%-75% after a second dose, and increased to 85% after a third dose. While prototypical antibody-secreting cells (ASCs) and T follicular helper (Tfh) cell responses were elicited in healthy participants, hematology patients showed prolonged ASCs and skewed Tfh2/17 responses. Importantly, vaccine-induced expansions of spike-specific and peptide-HLA tetramer-specific CD4+/CD8+ T cells, together with their T cell receptor (TCR) repertoires, were robust in hematology patients, irrespective of B cell numbers, and comparable to healthy participants. Vaccinated patients with breakthrough infections developed higher antibody responses, while T cell responses were comparable to healthy groups. COVID-19 vaccination induces robust T cell immunity in hematology patients of varying diseases and treatments irrespective of B cell numbers and antibody response.

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.

BACKGROUND: The Antifungal National Antimicrobial Prescribing Survey (AF-NAPS) was developed to undertake streamlined quality audits of antifungal prescribing. The validity and reliability of such tools is not characterized. OBJECTIVES: To assess the validity and reliability of the AF-NAPS quality assessment tool. METHODS: Case vignettes describing antifungal prescribing were prepared. A steering group was assembled to determine gold-standard classifications for appropriateness and guideline compliance. Infectious diseases physicians, antimicrobial stewardship (AMS) and specialist pharmacists undertook a survey to classify appropriateness and guideline compliance of prescriptions utilizing the AF-NAPS tool. Validity was measured as accuracy, sensitivity and specificity compared with gold standard. Inter-rater reliability was measured using Fleiss' kappa statistics. Assessors' responses and comments were thematically analysed to determine reasons for incorrect classification. RESULTS: Twenty-eight clinicians assessed 59 antifungal prescriptions. Overall accuracy of appropriateness assessment was 77.0% (sensitivity 85.3%, specificity 68.0%). Highest accuracy was seen amongst specialist (81%) and AMS pharmacists (79%). Prescriptions with lowest accuracy were in the haematology setting (69%), use of echinocandins (73%), mould-active azoles (75%) and for prophylaxis (71%). Inter-rater reliability was fair overall (0.3906), with moderate reliability amongst specialist pharmacists (0.5304). Barriers to accurate classification were incorrect use of the appropriateness matrix, knowledge gaps and lack of guidelines for some indications. CONCLUSIONS: The AF-NAPS is a valid tool, assisting assessors to correctly classify appropriate prescriptions more accurately than inappropriate prescriptions. Specialist and AMS pharmacists had similar performance, providing confidence that both can undertake AF-NAPS audits to a high standard. Identified reasons for incorrect classification w

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.

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.

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.

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.

Abstract 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.

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.

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.

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.

Aim To summarise the evidence on pharmacist‐led antifungal stewardship (AFS) programs in the hospital setting and to evaluate their impact on the quality of antifungal prescribing and infection management, antifungal usage and clinical outcomes. Data sources A systematic review of English‐language studies identified in MEDLINE and EMBASE was performed on 27 November 2020 and conducted in accordance with PRISMA. Search terms included ‘antifungal agent’, ‘invasive fungal infection’, ‘antimicrobial stewardship’, ‘patient care bundles’ and ‘pharmacist’. Study selection Eligible studies describing pharmacist‐led quality improvement intervention(s) implemented in the hospital setting targeted at optimising systemic antifungal prescribing. Results Six hundred and forty‐six studies were identified, and seven met inclusion criteria. Five were dedicated to optimising candidaemia management, one at optimising intensive care unit prescribing of caspofungin and one on antifungal prescribing in haematology and oncology units. All studies measured varied metrics relating to quality of prescribing and infection management, reporting improvement in proportion of effective antifungal therapy (n = 1/1), appropriate antifungal selection (n = 1/1), dosing (n = 2/3), management of drug–drug interactions (n = 1/1) and reduced time to antifungal initiation (n = 4/4). Studies that implemented a candidaemia bundle of care reported improvements in composite bundle adherence (n = 2/2), with greatest improvement in ophthalmological consultation (n = 4/4), echocardiography (n = 2/2) and infectious diseases consultation (n = 3/3). There was reduction in antifungal expenditure (n = 4/4) and consumption (n = 2/4). Pharmacist‐led AFS programs did not influence clinical outcomes. Conclusion Available evidence suggests that pharmacist‐led AFS interventions can improve the quality and timeliness of antifungal prescribing and reduce antifungal usage. Further research is required to assess the i

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.

BACKGROUND:The timing and necessity of repeated blood cultures (BCs) in children with cancer and febrile neutropenia (FN) are unknown. We evaluated the diagnostic yield of BCs collected pre- and post-empiric FN antibiotics. METHODS:Data collected prospectively from the Australian Predicting Infectious ComplicatioNs in Children with Cancer (PICNICC) study were used. Diagnostic yield was calculated as the number of FN episodes with a true bloodstream infection (BSI) detected divided by the number of FN episodes that had a BC taken. RESULTS:A BSI was identified in 13% of 858 FN episodes. The diagnostic yield of pre-antibiotic BCs was higher than of post-antibiotic cultures (12.3% vs 4.4%, P < .001). Two-thirds of the post-antibiotic BSIs were associated with a new episode of fever or clinical instability, and only 2 new BSIs were identified after 48 hours of empiric antibiotics and persistent fever. A contaminated BC was identified more frequently in post-antibiotic cultures. CONCLUSIONS:In the absence of new fever or clinical instability, BCs beyond 48 hours of persistent fever have limited yield. Opportunity exists to optimize BC collection in this population and reduce the burden of unnecessary tests on patients, healthcare workers, and hospitals.

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.

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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: Invasive fungal infection (IFI) detection requires application of complex case definitions by trained staff. Administrative coding data (ICD-10-AM) may provide a simplified method for IFI surveillance, but accuracy of case ascertainment in children with cancer is unknown. OBJECTIVE: To determine the classification performance of ICD-10-AM codes for detecting IFI using a gold-standard dataset (r-TERIFIC) of confirmed IFIs in paediatric cancer patients at a quaternary referral centre (Royal Children's Hospital) in Victoria, Australia from 1st April 2004 to 31st December 2013. METHODS: ICD-10-AM codes denoting IFI in paediatric patients (<18-years) with haematologic or solid tumour malignancies were extracted from the Victorian Admitted Episodes Dataset and linked to the r-TERIFIC dataset. Sensitivity, positive predictive value (PPV) and the F1 scores of the ICD-10-AM codes were calculated. RESULTS: Of 1,671 evaluable patients, 113 (6.76%) had confirmed IFI diagnoses according to gold-standard criteria, while 114 (6.82%) cases were identified using the codes. Of the clinical IFI cases, 68 were in receipt of ≥1 ICD-10-AM code(s) for IFI, corresponding to an overall sensitivity, PPV and F1 score of 60%, respectively. Sensitivity was highest for proven IFI (77% [95% CI: 58-90]; F1 = 47%) and invasive candidiasis (83% [95% CI: 61-95]; F1 = 76%) and lowest for other/unspecified IFI (20% [95% CI: 5.05-72%]; F1 = 5.00%). The most frequent misclassification was coding of invasive aspergillosis as invasive candidiasis. CONCLUSION: ICD-10-AM codes demonstrate moderate sensitivity and PPV to detect IFI in children with cancer. However, specific subsets of proven IFI and invasive candidiasis (codes B37.x) are more accurately coded.

Background: Reduced intensity treatment of low-risk febrile neutropenia (FN) in children with cancer is safe and improves quality of life. Identifying children with low-risk FN using a validated risk stratification strategy is recommended. This study prospectively validated nine FN clinical decision rules (CDRs) designed to predict infection or adverse outcome. Methods: Data were collected on consecutive FN episodes in this multicentre, prospective validation study. The reproducibility and discriminatory ability of each CDR in the validation cohort was compared to the derivation dataset and details of missed outcomes were reported. Findings: There were 858 FN episodes in 462 patients from eight hospitals included. Bacteraemia occurred in 111 (12·9%) and a non-bacteraemia microbiological documented infection in 185 (21·6%). Eight CDRs exhibited reproducibility and sensitivity ranged from 64% to 96%. Rules that had >85% sensitivity in predicting outcomes classified few patients (<20%) as low risk. For three CDRs predicting a composite outcome of any bacterial or viral infection, the sensitivity and discriminatory ability improved for prediction of bacterial infection alone. Across all CDRs designed to be implemented at FN presentation, the sensitivity improved at day 2 assessment. Interpretation: While reproducibility was observed in eight out of the nine CDRs, no rule perfectly differentiated between children with FN at high or low risk of infection. This is in keeping with other validation studies and highlights the need for additional safeguards against missed infections or adverse outcomes before implementation can be considered.

INTRODUCTION: A pandemic coronavirus, SARS-CoV-2, causes COVID-19, a potentially life-threatening respiratory disease. Patients with cancer may have compromised immunity due to their malignancy and/or treatment, and may be at elevated risk of severe COVID-19. Community transmission of COVID-19 could overwhelm health care services, compromising delivery of cancer care. This interim consensus guidance provides advice for clinicians managing patients with cancer during the pandemic. MAIN RECOMMENDATIONS: During the COVID-19 pandemic: In patients with cancer with fever and/or respiratory symptoms, consider causes in addition to COVID-19, including other infections and therapy-related pneumonitis. For suspected or confirmed COVID-19, discuss temporary cessation of cancer therapy with a relevant specialist. Provide information on COVID-19 for patients and carers. Adopt measures within cancer centres to reduce risk of nosocomial SARS-CoV-2 acquisition; support population-wide social distancing; reduce demand on acute services; ensure adequate staffing; and provide culturally safe care. Measures should be equitable, transparent and proportionate to the COVID-19 threat. Consider the risks and benefits of modifying cancer therapies due to COVID-19. Communicate treatment modifications, and review once health service capacity allows. Consider potential impacts of COVID-19 on the blood supply and availability of stem cell donors. Discuss and document goals of care, and involve palliative care services in contingency planning. CHANGES IN MANAGEMENT AS A RESULT OF THIS STATEMENT: This interim consensus guidance provides a framework for clinicians managing patients with cancer during the COVID-19 pandemic. In view of the rapidly changing situation, clinicians must also monitor national, state, local and institutional policies, which will take precedence. ENDORSED BY: Australasian Leukaemia and Lymphoma Group; Australasian Lung Cancer Trials Group; Australian and New Zealand Childre

BACKGROUND: Despite fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) being funded only for staging and restaging of some malignancies in Australia, there is evidence of benefit of FDG-PET/CT for infection indications such as pyrexia of unknown origin (PUO), prolonged neutropenic fever (NF) and prosthetic device infection. AIM: To evaluate the current knowledge, utilisation of and gaps in access to FDG-PET/CT for infectious indications by Australasian infectious diseases (ID) physicians and microbiologists. METHODS: An online survey was administered to ID and microbiology doctors practising in adult medicine in Australia and New Zealand through two established email networks. Using targeted questions and case-based examples, multiple themes were explored, including access to FDG-PET/CT, use and perceived benefit of FDG-PET/CT in diagnosis and monitoring of non-malignant conditions such as NF and PUO, and barriers to clinical use of FDG-PET/CT. RESULTS: A response was received from 120 participants across all states and territories. Onsite and offsite FDG-PET/CT access was 63% and 31% respectively. Eighty-six percent reported using FDG-PET/CT for one or more infection indications and all had found it clinically useful, with common indications being PUO, prosthetic device infections and use in the immunocompromised host for prolonged NF and invasive fungal infection. Thirty-eight percent reported barriers in accessing FDG-PET/CT for infection indications and 76% would utilise FDG-PET/CT more frequently if funding existed for infection indications. CONCLUSION: Access to FDG-PET/CT in Australia and New Zealand is modest and is limited by lack of reimbursement for infection indications. There is discrepancy between recognised ID indications for FDG-PET/CT and funded indications.

PURPOSE: Sepsis is a significant complication following cancer surgery. Although standardised care bundles improve sepsis outcomes in other populations, the benefits in cancer patients are unclear. The objectives of this study were to describe the epidemiology of sepsis in cancer patients post-surgery, and to evaluate the impact of a clinical sepsis pathway on management and clinical outcomes. METHODS: A standardised hospital-wide sepsis pathway was developed in 2013, and all cases of sepsis at the Peter MacCallum Cancer Centre in 2014 were retrospectively evaluated. Inclusion criteria were sepsis onset during the 100-day period following a surgical procedure for cancer diagnosis. Patients were identified using ICD-10-AM sepsis discharge codes, audit documentation and the hospital's antimicrobial approval system. Sepsis episodes were classified as managed on- or off-pathway. RESULTS: A total of 119 sepsis episodes were identified. Of these, 71 (59.7%) were managed on the sepsis pathway. Episodes managed on-pathway resulted more frequently in administration of appropriate antibiotics compared to those off-pathway (94.4% vs. 66.7%, p < 0.001), and had shorter time to first-dose antibiotics (median 85 vs. 315 min, p < 0.001). Pathway utilisation was associated with significant reductions in need for inotropes (7% vs. 13%, p = 0.023), ventilation (3% vs. 10%, p = 0.006) and length of hospitalisation (median 15 vs. 30 days, p = 0.008). The most frequent source of infection was organ-space surgical site infection (24.4% of instances). CONCLUSIONS: A dedicated hospital-wide sepsis pathway had significant impact on the quality of care and clinical outcomes of sepsis in cancer surgery patients. Cost-benefit analysis of sepsis pathways for cancer patients is required.

To date, very few studies have addressed nonneutropenic fever (NNF) in children with cancer, and there are no consensus guidelines. This scoping review aims to describe the rate of bacteremia, risk factors for infection and management, and outcomes of NNF in this population. Across 15 studies (n = 4106 episodes), the pooled-average bacteremia rate was 8.2%, and risk factors included tunneled external central venous catheter, clinical instability, and higher temperature. In two studies, antibiotics were successfully withheld in a subset of low-risk patients. Overall outcomes of NNF appear favorable; however, further research is required to determine its true clinical and economic impact.

Antibiotic allergies are reported in up to 1 in 4 immunocompromised hosts with significant impacts on antibiotic utilization and patient outcomes. Health services programs focused on de-labeling beta-lactam and sulfonamide allergy labels should be a standard of care in immunocompromised hosts.

AIM: Variation in the management of fever and neutropenia (FN) in children is well described. The aim of this study was to explore the current management of FN across Australia and New Zealand and highlight areas for improvement. METHODS: A practice survey was administered to paediatric health-care providers via four clinical and research networks. Using three clinical case vignettes, we explored risk stratification, empiric antibiotics, initial investigations, intravenous-oral switch, ambulatory management and antibiotic duration in children with cancer and FN. RESULTS: A response was received from 104 participants from 16 different hospitals. FN guideline compliance was rated as moderate or poor by 24% of respondents, and seven different fever definitions were described. There was little variation in the selected empiric monotherapy and dual-therapy regimens, and almost all respondents recommended first-dose antibiotics within 1 h. However, 27 different empiric antibiotic combinations were selected for beta-lactam allergy. An incorrect risk status was assigned to the low-risk case by 27% of respondents and to the high-risk case by 41%. Compared to current practice, significantly more respondents would manage the low-risk case in the ambulatory setting provided adequate resources were in place (43 vs. 85%, P < 0.0001). There was variation in the use of empiric glycopeptides as well as use of aminoglycosides beyond 48 h. CONCLUSION: Although the antibiotics selected for empiric management of FN are appropriate and consistent, variation and inaccuracies exist in risk stratification, the selection of monotherapy over dual therapy, empiric antibiotics chosen for beta-lactam allergy, use of glycopeptides and duration of aminoglycosides.

Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved. Background: Fever and neutropenia (FN) clinical decision rules (CDRs) are recommended to help distinguish children with cancer at high and low risk of severe infection. The aim of this study was to validate existing pediatric FN CDRs designed to stratify children with cancer at high or low risk of serious infection or medical complication. Methods: Pediatric CDRs suitable for validation were identified from a literature search. Relevant data were extracted from an existing data set of 650 retrospective FN episodes in children with cancer. The sensitivity and specificity of each of the CDR were compared with the derivation studies to assess reproducibility. Results: Six CDRs were identified for validation: 2 were designed to predict bacteremia and 4 to predict adverse events. Five CDRs exhibited reproducibility in our cohort. A rule predicting bacteremia had the highest sensitivity (100%; 95% confidence interval (CI): 93%-100%) although poor specificity (17%), with only 15% identified as low risk. For adverse events, the highest sensitivity achieved was 84% (95% CI: 75%-90%), with specificity of 29% and 27% identified as low risk. A rule intended for application after a 24-hour period of inpatient observation yielded a sensitivity of 80% (95% CI: 73-86) and specificity of 46%, with 44% identified as low risk. Conclusions: Five CDRs were reproducible, although not all can be recommended for implementation because of either inadequate sensitivity or failure to identify a clinically meaningful number of low-risk patients. The 24-hour rule arguably exhibits the best balance between sensitivity and specificity in our population.

BACKGROUND: The aim of this study was to validate the 'Predicting Infectious ComplicatioNs in Children with Cancer' (PICNICC) clinical decision rule (CDR) that predicts microbiologically documented infection (MDI) in children with cancer and fever and neutropenia (FN). We also investigated costs associated with current FN management strategies in Australia. METHODS: Demographic, episode, outcome and cost data were retrospectively collected on 650 episodes of FN. We assessed the discrimination, calibration, sensitivity and specificity of the PICNICC CDR in our cohort compared with the derivation data set. RESULTS: Using the original variable coefficients, the CDR performed poorly. After recalibration the PICNICC CDR had an area under the receiver operating characteristic (AUC-ROC) curve of 0.638 (95% CI 0.590-0.685) and calibration slope of 0.24. The sensitivity, specificity, positive predictive value and negative predictive value of the PICNICC CDR at presentation was 78.4%, 39.8%, 28.6% and 85.7%, respectively. For bacteraemia, the sensitivity improved to 85.2% and AUC-ROC to 0.71. Application at day 2, taking into consideration the proportion of MDI known (43%), further improved the sensitivity to 87.7%. Length of stay is the main contributor to cost of FN treatment, with an average cost per day of AUD 2183 in the low-risk group. CONCLUSIONS: For prediction of any MDI, the PICNICC rule did not perform as well at presentation in our cohort as compared with the derivation study. However, for bacteraemia, the predictive ability was similar to that of the derivation study, highlighting the importance of recalibration using local data. Performance also improved after an overnight period of observation. Implementation of a low-risk pathway, using the PICNICC CDR after a short period of inpatient observation, is likely to be safe and has the potential to reduce health-care expenditure.

BACKGROUND: A translational study in patients with myeloma to determine the utility of immune profiling to predict infection risk in patients with hematological malignancy was conducted. METHODS: Baseline, end of induction, and maintenance peripheral blood mononuclear cells from 40 patients were evaluated. Immune cell populations and cytokines released from 1 × 106 cells/ml cultured in the presence of a panel of stimuli (cytomegalovirus, influenza, S. pneumoniae, phorbol myristate acetate/ionomycin) and in media alone were quantified. Patient characteristics and infective episodes were captured from clinical records. Immunological variables associated with increased risk for infection in the 3-month period following sample collection were identified using univariate analysis (p < 0.05) and refined with multivariable analysis to define a predictive immune profile. RESULTS: 525 stimulant samples with 19,950 stimulant-cytokine combinations across three periods were studied, including 61 episodes of infection. Mitogen-stimulated release of IL3 and IL5 were significantly associated with increased risk for subsequent infection during maintenance therapy. A lower Th1/Th2 ratio and higher cytokine response ratios for IL5 and IL13 during maintenance therapy were also significantly associated with increased risk for infection. On multivariable analysis, only IL5 in response to mitogen stimulation was predictive of infection. The lack of cytokine response and numerical value of immune cells were not predictive of infection. CONCLUSION: Profiling cytokine release in response to mitogen stimulation can assist with predicting subsequent onset of infection in patients with hematological malignancy during maintenance therapy.

Antimicrobials are widely used in veterinary practices, but there has been no investigation of antimicrobial classes used or the appropriateness of their use in bovine practice. This study investigated antimicrobial use for surgical prophylaxis in bovine practice in Australia. A cross-sectional study of veterinarian antimicrobial usage patterns was conducted using an online questionnaire. Information solicited included respondent's details, the frequency with which antimicrobials were used for specific surgical conditions (including the dose, timing and duration of therapy) and details of practice antimicrobial use policies and sources of information about antimicrobials. In total, 212 members of the Australian veterinary profession working in bovine practice completed the survey. Antimicrobials were always or frequently used by more than 75 per cent of respondents in all scenarios. Generally, antimicrobial drug choice was appropriate for the reported surgical conditions. Procaine penicillin and oxytetracycline accounted for 93 per cent of use. However, there was a wide range of doses used, with underdosing and inappropriate timing of administration being common reasons for inappropriate prophylactic treatment. There was very low use of critically important antimicrobials (3.3 per cent of antimicrobials reported). Antimicrobial use guidelines need to be developed and promoted to improve the responsible use of antimicrobials in bovine practice.

BACKGROUND: Identifying themes associated with inappropriate prescribing in Australian public and private hospitals will help target future antimicrobial stewardship initiatives. AIMS: To describe current antimicrobial prescribing practices, identify similarities and differences between hospital sectors and provide target areas for improvement specific to each hospital sector. METHODS: All hospitals included in the study were part of the 2014 national antimicrobial prescribing survey and conducted one of the following: a whole hospital point prevalence survey, serial point prevalence surveys or a sample of randomly selected patients. Data on the types of antibiotics used, their indications for use and the quality of prescription based on compliance with national and local prescribing guidelines were collected. RESULTS: Two hundred and two hospitals (166 public and 36 private) comprising 10 882 patients and 15 967 antimicrobial prescriptions were included. Public hospitals had higher proportions of prescriptions for treatment (81.5% vs 48.4%) and medical prophylaxis (8.8% and 4.6%), whilst private hospitals had significantly higher surgical prophylaxis use (9.6% vs 46.9%) (P < 0.001). In public hospitals, the main reasons for non-compliance of treatment prescriptions were spectrum being too broad (30.5%) while in private it was incorrect dosing. Prolonged duration was the main reason for non-compliance among surgical prophylaxis prescriptions in both types of hospitals. CONCLUSIONS: Australian hospitals need to target specific areas to improve antimicrobial use. Specifically, unnecessary broad-spectrum therapy should be a priority area in public hospitals, whilst emphasis on curtailing antimicrobial overuse in surgical prophylaxis needs to be urgently addressed across in the private hospital sector.

Antibiotic allergy testing (AAT) practices of Emerging Infections Network infectious disease physicians were surveyed. Although AAT was perceived to be necessary for removal of inappropriate or unnecessary allergy labels, there was limited access to any form of testing. In this study, we discuss current antibiotic allergy knowledge gaps and the development of AAT practices within antimicrobial stewardship programs, which will potentially improve antimicrobial prescribing.

INTRODUCTION: Infections are a leading cause of morbidity and mortality in patients with multiple myeloma. The epidemiology, risk factors and outcomes of viral respiratory tract infections (vRTI) are not well described in patients with multiple myeloma managed with novel agents, the current standard of care. METHODS: Patients with myeloma from 2009 to 2012 who tested positive on respiratory virus multiplex polymerase chain reaction had clinical, radiological and microbiological records reviewed. The Fourth European Conference on Infections in Leukaemia (ECIL-4) definitions of RTI were applied. Univariate and multivariate regression analysis of risk factors was performed using vRTI as the evaluable outcome. RESULTS: Of 330 patients, 75 (22.7%) tested positive for a total of 100 vRTI episodes. All patients received thalidomide, lenalidomide or bortezomib in combination with myeloma therapies (median of three treatment regimens). vRTI occurred most commonly in patients with progressive disease, and receipt of more than three lines of myeloma therapy was associated with an increased risk of vRTI (p < 0.01). Amongst key respiratory pathogens, influenza was associated with the highest hospital admission rate (66.7%), ICU admission rate (41.6%) and mortality (33.3%) whilst RSV was associated with prolonged hospital stay. CONCLUSION: Patients with multiple myeloma and advanced disease managed with multiple lines of therapy are at risk for vRTI, and targeted interventions for prevention/treatment are required.

BACKGROUND: Antibiotic allergy labels are associated with sub-optimal prescribing patterns and poorer clinical outcomes in non-cancer populations, but the effect of labelling on antimicrobial usage in patients with cancer is unknown. FINDINGS: A retrospective review of hospitalized patients admitted to the Peter MacCallum Cancer Centre (2010-2012) identified 23 % of cancer patients (n = 198) with an antimicrobial allergy label (AA). Comparison of those with an antimicrobial allergy label to those without demonstrated increased antibiotic use per admission (3 vs. 2, p = 0.01), increased fluoroquinolone use (11 % vs. 6 %, p < 0.05), increased antibiotic course duration (15 vs. 13 days, p = 0.09), higher readmission rates (53 % vs. 28 %, p < 0.001) and poorer concordance with prescribing guidelines (47 % vs. 91 %, p < 0.001). Patients in the AA group on multivariate analysis had a higher number of antibiotics employed, longer duration of antibiotic therapy and higher rate of readmission. CONCLUSIONS: Antimicrobial usage, including the use of restricted antibiotics, is higher in patients with cancer. Antibiotic de-labelling strategies in cancer patients must be evaluated to aid antimicrobial stewardship initiatives.

PURPOSE: Prospective surveillance of invasive mold diseases (IMDs) in haematology patients should be standard of care but is hampered by the absence of a reliable laboratory prompt and the difficulty of manual surveillance. We used a high throughput technology, natural language processing (NLP), to develop a classifier based on machine learning techniques to screen computed tomography (CT) reports supportive for IMDs. PATIENTS AND METHODS: We conducted a retrospective case-control study of CT reports from the clinical encounter and up to 12-weeks after, from a random subset of 79 of 270 case patients with 33 probable/proven IMDs by international definitions, and 68 of 257 uninfected-control patients identified from 3 tertiary haematology centres. The classifier was trained and tested on a reference standard of 449 physician annotated reports including a development subset (n = 366), from a total of 1880 reports, using 10-fold cross validation, comparing binary and probabilistic predictions to the reference standard to generate sensitivity, specificity and area under the receiver-operating-curve (ROC). RESULTS: For the development subset, sensitivity/specificity was 91% (95%CI 86% to 94%)/79% (95%CI 71% to 84%) and ROC area was 0.92 (95%CI 89% to 94%). Of 25 (5.6%) missed notifications, only 4 (0.9%) reports were regarded as clinically significant. CONCLUSION: CT reports are a readily available and timely resource that may be exploited by NLP to facilitate continuous prospective IMD surveillance with translational benefits beyond surveillance alone.

BACKGROUND: The ideal method to encourage uptake of clinical guidelines in hospitals is not known. Several strategies have been suggested. This study evaluates the impact of academic detailing and a computerised decision support system (CDSS) on clinicians' prescribing behaviour for patients with community acquired pneumonia (CAP). METHODS: The management of all patients presenting to the emergency department over three successive time periods was evaluated; the baseline, academic detailing and CDSS periods. The rate of empiric antibiotic prescribing that was concordant with recommendations was studied over time comparing pre and post periods and using an interrupted time series analysis. RESULTS: The odds ratio for concordant therapy in the academic detailing period, after adjustment for age, illness severity and suspicion of aspiration, compared with the baseline period was OR = 2.79 [1.88, 4.14], p < 0.01, and for the computerised decision support period compared to the academic detailing period was OR = 1.99 [1.07, 3.69], p = 0.02. During the first months of the computerised decision support period an improvement in the appropriateness of antibiotic prescribing was demonstrated, which was greater than that expected to have occurred with time and academic detailing alone, based on predictions from a binary logistic model. CONCLUSION: Deployment of a computerised decision support system was associated with an early improvement in antibiotic prescribing practices which was greater than the changes seen with academic detailing. The sustainability of this intervention requires further evaluation.

Pneumocystis jirovecii pneumonia (PCP) is associated with high mortality in immunocompromised patients without human immunodeficiency virus infection. However, chemoprophylaxis is highly effective. In patients with solid tumours or haematologic malignancy, several risk factors for developing PCP have been identified, predominantly corticosteroid therapy. The aims of this study were to identify the potentially preventable cases of PCP in patients receiving corticosteroid therapy at a tertiary care cancer centre and to estimate the frequency of utilisation of chemoprophylaxis in these patients. Two retrospective reviews were performed. Over a 10-year period, 14 cases of PCP were identified: no cases were attributable to failed chemoprophylaxis, drug allergy or intolerance. During a 6-month period, 73 patients received high-dose corticosteroid therapy (> or =25 mg prednisolone or > or =4 mg dexamethasone daily) for > or =4 weeks. Of these, 22 (30%) had haematologic malignancy, and 51 (70%) had solid tumours. Fewer patients with solid tumours received prophylaxis compared to patients with haematologic malignancy (3.9 vs 63.6%, P<0.0001). Guidelines for PCP chemoprophylaxis in patients with haematologic malignancy or solid tumours who receive corticosteroid therapy are proposed. Successful primary prevention of PCP in this population will require a multifaceted approach targeting the suboptimal prescribing patterns for chemoprophylaxis.