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Introduction: Antifungal prophylaxis is an important preventative strategy for high-risk pediatric oncology patients. When triazoles are contraindicated, micafungin is an alternative to polyenes, due to improved tolerability and limited drug-drug interactions. An intermittent dosing schedule is advantageous for outpatient parenteral antimicrobial therapy (OPAT), but studies assessing safety in pediatric patients are limited. Methods: This single-centre, retrospective, observational study compared the safety and tolerability of daily (1 mg/kg) and intermittent (3 mg/kg) dosing of amphotericin B liposomal (AmB) and micafungin in children under 18 years, with high-risk leukemia. ResultsOf 51 patients, with 76 individual dosing schedules, hepatoxicity and nephrotoxicity were comparable across all four dosing schedules. Severity of hypokalemia was significantly higher amongst patients receiving AmB (p = 0.041), with higher rates of intravenous electrolyte supplementation required. Infusion-related reactions occurred only in the AmB group (22 %). Intermittent administration and dosing of micafungin was well tolerated, with similar effects on liver function and reduced rates of hypokalemia. Conclusion: This study supports the positive safety profile of intermittent micafungin compared with AmB and describes successful OPAT implementation. Prospective studies assessing efficacy are needed to validate these findings.

Summary: Background: Prompt antibiotic administration for febrile neutropenia (FN) is standard of care, and targets of time to antibiotics (TTA)

Summary: Background: New and emerging risks for invasive aspergillosis (IA) bring the need for contemporary analyses of the epidemiology and outcomes of IA, in order to improve clinical practice. Methods: The study was a retrospective, multicenter, cohort design of proven and probable IA in adults from 10 Australasian tertiary centres (January 2017–December 2020). Descriptive analyses were used to report patients’ demographics, predisposing factors, mycological characteristics, diagnosis and management. Accelerated failure-time model was employed to determine factor(s) associated with 90-day all-cause mortality (ACM). Findings: Of 382 IA episodes, 221 (in 221 patients) fulfilled inclusion criteria – 53 proven and 168 probable IA. Median patient age was 61 years (IQR 51–69). Patients with haematologic malignancies (HM) comprised 49.8% of cases. Fifteen patients (6.8%) had no pre-specified immunosuppression and eleven patients (5.0%) had no documented comorbidity. Only 30% of patients had neutropenia. Of 170 isolates identified, 40 (23.5%) were identified as non-Aspergillus fumigatus species complex. Azole-resistance was present in 3/46 (6.5%) of A. fumigatus sensu stricto isolates. Ninety-day ACM was 30.3%. HM (HR 1.90; 95% CI 1.04–3.46, p = 0.036) and ICU admission (HR 4.89; 95% CI 2.93–8.17, p

Cytomegalovirus (CMV) is a ubiquitous virus which causes a mild illness in healthy individuals. In immunocompromised individuals, such as children receiving haematopoietic stem cell transplantation, CMV can reactivate, causing serious disease and increasing the risk of death. CMV can be effectively treated with antiviral drugs, but antiviral resistance is an increasingly common complication. Available therapies are associated with adverse effects such as bone marrow suppression and renal impairment, making the choice of appropriate treatment challenging. New agents are emerging and require evaluation in children to establish their role. This review will discuss established and emerging diagnostic tools and treatment options for CMV, including antiviral resistant CMV, in children undergoing haematopoietic stem cell transplant.

Altered mental status is a major criterion for a diagnosis of encephalitis to be made with alteration in behavior, a key manifestation of altered mental status. We reviewed all evaluated cases identified by the Australian Childhood Encephalitis study between May 2013 and June 2018, to review the frequency and features of altered behavior (ALB). ALB was reported in >72% of cases of childhood encephalitis in all three major etiologic groups (infectious, immune-mediated, and unknown). The duration of ALB was >7 days in a minority, but significantly more frequent in immune-mediated compared with infectious encephalitis (27 and 10%, respectively, p < 0.01). ALB was most frequently characterized as irritability/agitation (47%), which predominated in children aged 1 year and most frequent in immune-mediated encephalitis. Hallucinations, paranoia, and aggression were all infrequent; suicidality/self-harm was not observed. ALB was reported in 20 of 21 cases of anti-N-methyl-d-aspartate receptor (anti-NMDAr), 19% for >7 days, and disorientation/confusion was the most frequent feature. Only one case was reported as presenting with “psychosis” and was diagnosed with anti-NMDAr encephalitis. Clinician-reported ALB is frequent but most often non-specific in childhood encephalitis. A longer duration of ALB is associated with an immune-mediated cause. More specific psychiatric symptoms (hallucinations, paranoia) are very infrequent. ALB is a hallmark of anti-NMDAr encephalitis, but psychosis is uncommon in contrast to the disorder in adults.

Abstract Objectives Invasive group A Streptococcus (iGAS) disease is serious and sometimes life-threatening. The Paediatric Active Enhanced Disease Surveillance (PAEDS) Network collects voluntary notifications from seven major Australian paediatric hospitals on patients with certain conditions, including iGAS disease. Our aims were to: 1) Describe the epidemiological distribution of paediatric iGAS disease in Australia and correlate this with influenza notifications, 2) Identify GAS strains commonly associated with invasive disease in children. Methods IGAS and influenza notification data were obtained (from the PAEDS Network and the Australian Institute of Health and Welfare, respectively, for the period 1 July 2016 to 30 June 2018). Included iGAS patients had GAS isolated from a normally sterile body site. Data were described according to selected clinical and demographic characteristics, including by age group and Australian State, with proportions and minimum incidence rates estimated. Results A total of 181 patients were identified, with most (115, 63.5%)

ObjectivesFebrile 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.MethodsThirty-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.ResultsThe 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.ConclusionElevated 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.

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 (

An amendment to this paper has been published and can be accessed via the original article.

Objectives Timely intravenous-to-oral antibiotic switching for children is important for paediatric antimicrobial stewardship (AMS). However, low decision-making confidence and fragmentation of patient care can hamper implementation, with difficulties heightened regionally where AMS programmes for children are lacking. The aim of this study was to develop and evaluate user-led creation and implementation of an intervention package for early intravenous-to-oral switching at regional hospitals in Queensland, Australia.Design Guided by theory, a four-phase approach was used to: (1) develop multifaceted intervention materials; (2) review materials and their usage through stakeholders; (3) adapt materials based on user-feedback and (4) qualitatively evaluate health workers experiences at 6 months postintervention.Setting Seven regional hospitals in Queensland, Australia.Participants Phase 2 included 15 stakeholders; health workers and patient representatives (patient-guardians and Indigenous liaison officers). Phase 4 included 20 health workers across the seven intervention sites.Results Content analysis of health worker and parent/guardian reviews identified the ‘perceived utility of materials’ and ‘possible barriers to use’. ‘Recommendations and strategies for improvement’ provided adjustments for the materials that were able to be tailored to individual practice. Postintervention interviews generated three overarching themes that combined facilitators and barriers to switching: (1) application of materials, (2) education and support, and (3) team dynamics. Overall, despite difficulties with turnover and problems with the medical hierarchy, interventions aided and empowered antibiotic therapy decision-making and enhanced education and self-reflection.Conclusions Despite structural barriers to AMS for switching from intravenous-to-oral antibiotics in paediatric patients, offering a tailored multifaceted intervention was reported to provide support and confidence to adjust practice across a diverse set of health workers in regional areas. Future AMS activities should be guided by users and provide opportunities for tailoring tools to practice setting and patients’ requirements.

Abstract 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.

Objective To present Australia-wide data on paediatric COVID-19 and multisystem inflammatory syndromes to inform health service provision and vaccination prioritisation.Design Prospective, multicentre cohort study.Setting Eight tertiary paediatric hospitals across six Australian states and territories in an established research surveillance network—Paediatric Active Enhanced Disease (PAEDS).Participants All children aged

Introduction: Biologic disease-modifying anti-rheumatic drugs (bDMARDS) are increasingly used in clinical practice for a variety of conditions. Due to concerns surrounding persistence of drug levels and resulting immunosuppression, current case reports recommend against live vaccine administration in the first year of life for an infant exposed to perinatal bDMARDS. As a result, this significantly impacts receipt of rotavirus vaccination, a vaccine recommended in many countries’ national immunization program. Area covered: We have reviewed all available published literature to explore the effect of peripartum bDMARDS exposure on infant immune responses, safety of live vaccines, and vaccine efficacy in the first year of life. Expert opinion: We recommend that otherwise healthy newborns with a history of perinatal exposure to bDMARDS should receive rotavirus vaccinations as per the recommended schedule. Bacille Calmette et Guerin vaccine should be withheld in the first year of life. No additional booster doses of inactivated vaccines are required as they appear to mount adequate immune responses to the routine schedule.

BackgroundInvasive 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.ObjectiveTo 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.MethodsICD-10-AM codes denoting IFI in paediatric patients (ResultsOf 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.ConclusionICD-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.

World Health Organization (WHO) radiological classification remains an important entry criterion in epidemiological studies of pneumonia in children. We report inter-observer variability in the interpretation of 169 chest radiographs in children suspected of having pneumonia.An 18-month prospective aetiological study of pneumonia was undertaken in Northern England. Chest radiographs were performed on eligible children aged ≤16 years with clinical features of pneumonia. The initial radiology report was compared with a subsequent assessment by a consultant cardiothoracic radiologist. Chest radiographic changes were categorised according to the WHO classification.There was significant disagreement (22%) between the first and second reports (kappa = 0.70, P