Search

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/mm 3 . 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., (© 2022 Australasian College for Emergency Medicine.)

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., (© 2021 Wiley Periodicals LLC.)

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., (© 2021 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Doerflinger, Haeusler, Li-Wai-Suen, Clark, Slavin, Babl, Allaway, Mechinaud, Smyth, De Abreu Lourenco, Phillips, Pellegrini and Thursky.)

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Home-based management of low-risk febrile neutropenia (FN) is safe, improves quality of life and reduces healthcare expenditure. A formal low-risk paediatric program has not been implemented in Australia. We aimed to describe the implementation process and evaluate the clinical impact., Method: This prospective study incorporated three phases: implementation, intervention and evaluation. A low-risk FN implementation toolkit was developed, including a care-pathway, patient information, home-based assessment and educational resources. The program had executive-level endorsement, a multidisciplinary committee and a nurse specialist. Children with cancer and low-risk FN were eligible to be transferred home with a nurse visiting daily after an overnight period of observation for intravenous antibiotics. Low-risk patients were identified using a validated decision rule, and suitability for home-based care was determined using disease, chemotherapy and patient-level criteria. Plan-Do-Study-Act methodology was used to evaluate clinical impact and safety., Results: Over 18 months, 292 children with FN were screened: 132 (45%) were low-risk and 63 (22%) were transferred to home-based care. Compared with pre-implementation there was a significant reduction in in-hospital median LOS (4.0 to 1.5 days, p < 0.001) and 291 in-hospital bed days were saved. Eight (13%) patients needed readmission and there were no adverse outcomes. A key barrier was timely screening of all patients and program improvements, including utilising the electronic medical record for patient identification, are planned., Conclusion: This program significantly reduces in-hospital LOS for children with low-risk FN. Ongoing evaluation will inform sustainability, identify areas for improvement and support national scale-up of the program.

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. [ABSTRACT FROM AUTHOR]

Background: The use of fluoroquinolones to prevent infections in neutropenic patients with cancer or undergoing hematopoietic stem cell transplantation (HSCT) is a controversial issue, with international guidelines providing conflicting recommendations. Although potential benefits are clear, concerns revolve around efficacy, potential harms, and antimicrobial resistance (AMR) implications. Discussion: Fluoroquinolone prophylaxis reduces neutropenic fever (NF) bloodstream infections and other serious bacterial infections, based on evidence from systematic reviews, randomized controlled trials, and observational studies in adults and children. Fluoroquinolone prophylaxis may also reduce infection‐related morbidity and healthcare costs; however, evidence is conflicting. Adverse effects of fluoroquinolones are well recognized in the general population; however, studies in the cancer cohort where it is used for a defined period of neutropenia have not reflected this. The largest concern for routine use of fluoroquinolone prophylaxis remains AMR, as many, but not all, observational studies have found that fluoroquinolone prophylaxis might increase the risk of AMR, and some studies have suggested negative impacts on patient outcomes as a result. Conclusions: The debate surrounding fluoroquinolone prophylaxis calls for individualized risk assessment based on patient characteristics and local AMR patterns, and prophylaxis should be restricted to patients at the highest risk of serious infection during the highest risk periods to ensure that the risk‐benefit analysis is in favor of individual and community benefit. More research is needed to address important unanswered questions about fluoroquinolone prophylaxis in neutropenic patients with cancer or receiving HSCT. [ABSTRACT FROM AUTHOR]

Febrile neutropenia is a common complication experienced by children with cancer or those undergoing hematopoietic stem cell transplantation. Repeated episodes of febrile neutropenia result in cumulative exposure to broad-spectrum antibiotics with potential for a range of serious adverse effects. Short-course antibiotics, even in patients with high-risk febrile neutropenia, may offer a solution. This review addresses the known broad effects of antibiotics, highlights developments in understanding the relationship between cancer, antibiotics, and the gut microbiome, and discusses emerging evidence regarding long-term adverse antibiotic effects. The authors consider available evidence to guide the duration of empiric antibiotics in pediatric febrile neutropenia and directions for future research. Broad-spectrum antibiotics are associated with antimicrobial resistance, Clostridioides difficile infection, invasive candidiasis, significant disturbance of the gut microbiome and may seriously impact outcomes in children with cancer or undergoing allogenic hematopoietic stem cell transplant. Short-course empiric antibiotics are likely safe in most children with febrile neutropenia and present a valuable opportunity to reduce the risks of antibiotic exposure. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim: Fever in immunocompromised children presents significant challenges. We aimed to determine the clinical impact of fluorodeoxyglucose-positron emission tomography (FDG-PET) in combination with computed tomography (CT) in children with malignancy or following haematopoietic stem cell transplantation with prolonged or recurrent fever.Methods: Immunocompromised children who underwent FDG-PET/CT for investigation of prolonged or recurrent fever were identified from hospital databases. The clinical impact of the FDG-PET/CT was considered 'high' if it contributed to any of the following: diagnosis of a new site infection/inflammation, change to antimicrobials or chemotherapy, or additional investigations or specialist consult contributing to final diagnosis.Results: Fourteen patients underwent an FDG-PET/CT for prolonged or recurrent fever. Median age was 11 years and 46% had diagnosis of acute lymphoblastic leukaemia. The median absolute neutrophil count on the day of FDG-PET/CT was 0.47 cells/μL. The clinical impact of FDG-PET/CT was 'high' in 11 (79%) patients, contributing to rationalisation of antimicrobials in three, and cessation of antimicrobials in five. Compared to conventional imaging, FDG PET/CT identified seven additional sites of clinically significant infection/inflammation in seven patients. Of the 10 patients who had a cause of fever identified, FDG-PET/CT contributed to the final diagnosis in six (60%).Conclusion: This study has identified potential utility for FDG-PET/CT in immunocompromised children with prolonged or recurrent fever. Further prospective studies are needed to compare FDG-PET/CT versus conventional imaging, to identify the optimal timing of FDG-PET/CT and to study the role of subsequent scans to monitor response to therapy. [ABSTRACT FROM AUTHOR]

Background: Neutropenic fever (NF) is a common complication of cancer chemotherapy. Patients at low risk of medical complications from NF can be identified using a validated risk assessment and managed in an outpatient setting. This is a new model of care for Australia. This study described the implementation of a sustainable ambulatory program for NF at a tertiary cancer centre over a 12-month period.Methods: Peter MacCallum Cancer Centre introduced an ambulatory care program in 2014, which identified low-risk NF patients, promoted early de-escalation to oral antibiotics, and early discharge to a nurse-led ambulatory program. Patients prospectively enrolled in the ambulatory program were compared with a historical-matched cohort of patients from 2011 for analysis. Patient demographics, clinical variables (cancer type, recent chemotherapy, treatment intent, site of presentation) and outcomes were collected and compared. Total cost of inpatient admissions was determined from diagnosis-related group (DRG) codes and applied to both the prospective and historical cohorts to allow comparisons.Results: Twenty-five patients were managed in the first year of this program with a reduction in hospital median length of stay from 4.0 to 1.1 days and admission cost from Australian dollars ($AUD) 8580 to $AUD2360 compared to the historical cohort. Offsetting salary costs, the ambulatory program had a net cost benefit of $AUD 71895. Readmission for fever was infrequent (8.0%), and no deaths were reported.Conclusion: Of relevance to hospitals providing cancer care, feasibility, safety, and cost benefits of an ambulatory program for low-risk NF patients have been demonstrated. [ABSTRACT FROM AUTHOR]

We examine the infective complications occurring during azacitidine (AZA) therapy in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). A retrospective review of patients receiving ≥1 cycle of AZA for MDS or AML was performed. Patient demographics, infection prophylaxis/episodes and outcomes were evaluated. Sixty eight patients received 884 AZA cycles. Bacterial infections occurred in 25% of cycle-1 and 27% of cycle-2 AZA therapy. Febrile neutropenia complicated 5.3% of AZA cycles, bacteremia 2% and invasive Aspergillosis 0.3%. Using Poisson modeling, a very high IPSS-R (RR 10.26, 95% CI 1.20, 87.41,p= .033) was identified as an independent risk factor for infection. Infection-related attributable mortality was 23%. The burden of infection is high in AZA-treated patients, associated with high attributable mortality. Over 25% of AZA cycles 1 and 2 were complicated by infection, predominantly bacterial, rates dropping to <10% after cycle-5. [ABSTRACT FROM PUBLISHER]

Early and targeted antimicrobial therapy improves outcomes in patients with febrile neutropenia (FN). We evaluated the impact of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) on antimicrobial utilization in the management of FN. A cohort of patients with FN and hematological malignancy was identified. Cases (in whom FDG-PET was performed, n = 37) were compared with controls (in whom conventional investigations excluding FDG-PET were performed, n = 76). An underlying cause for FN was determined in 94.6% of cases, compared to 69.7% of controls. FDG-PET had a significant impact on antimicrobial utilization compared to conventional imaging (35.1% vs. 11.8%; p = 0.003), and was associated with shorter duration of liposomal amphotericin-B therapy for systemic fungal infection (median 4.0 days cases vs. 10.0 days controls; p = 0.001). Cases had a longer length of hospitalization ( p = 0.016). In the management of patients with high-risk FN, FDG-PET improves diagnostic yield and allows rationalization of antifungal therapy. The impact upon healthcare costs associated with antimicrobial therapy for FN requires further evaluation. [ABSTRACT FROM AUTHOR]