Utility of BioFire FilmArray Pneumonia Panel Plus in a High-Risk Cohort: Children Post Allogeneic Stem Cell Transplantation.

Introduction: Pulmonary complications due to infection contribute significantly to post-haematopoietic stem cell transplant (HCT) morbidity and mortality. Standard microbiological investigations, when performed on bronchoalveolar lavage (BAL) fluid, can take days to weeks to confirm a diagnosis. We aimed to determine the diagnostic performance of the BioFire FilmArray pneumonia panel plus (FA-PP), a multiplex polymerase chain reaction (PCR) panel that detects 18 bacterial and nine viral targets, when applied to BAL obtained by flexible bronchoscopy, in children undergoing HCT.

Relationship between posaconazole concentrations and clinical outcomes in paediatric cancer and haematopoietic stem cell transplant recipients.

Background: Posaconazole is used to prevent and treat invasive fungal infections (IFIs) in immunocompromised children, including those undergoing cancer treatment or HSCT. Despite differences in pharmacokinetics and IFI epidemiology between children and adults, therapeutic targets established in adult studies are often applied to children.

Objectives: This systematic review evaluated the correlation between serum posaconazole concentrations and clinical outcomes of IFI prophylaxis and treatment in children with malignancies or HSCT recipients.

Use of food restrictions to prevent infections in paediatric patients with cancer and haematopoietic cell transplantation recipients: a systematic review and clinical practice guideline.

Background: Food restrictions during periods of neutropenia have been widely used in oncology settings to prevent infections. As there is a lack of clearly demonstrated effectiveness, this strategy is being increasingly questioned.

Methods: A multi-national panel of 23 individuals was convened to develop a clinical practice guideline (CPG) on the use of food restrictions to prevent infections in paediatric patients with cancer and haematopoietic cell transplantation (HCT) recipients.

Antimicrobials for Neonates: Practitioner Decisions and Diagnostic Certainty.

Background: Antimicrobials are frequently prescribed to neonates who require hospital care, but the influences on clinical decision-making and practice variation in this process are ill-understood. We performed a cross-sectional survey of practitioners who prescribe antimicrobials in 3 Australian neonatal units.

Methods: During two 5-day data capture periods per center, 56 practitioners reported their general confidence in antimicrobial decision-making for neonates.

Systematic Review of the Presentation, Treatment, and Outcome of Chronic Disseminated Candidiasis in Children With Cancer or Following Hematopoietic Cell Transplant.

Chronic disseminated candidiasis (CDC) is a rare complication of immunosuppression. This review describes the presentation, management, and outcomes of CDC in pediatric patients with cancer or following hematopoietic cell transplant (HCT). PubMed, Embase, and Medline were searched identifying 32 studies, describing 95 cases of CDC.

Assessing the Theoretical Efficacy of Combination Therapy Against Gram-Negative Infections in Neutropenic Pediatric Cancer Patients: Insights from the Statistical Analysis of Survey Data.

: Empirical antibacterial therapy for febrile neutropenia reduces mortality due to Gram-negative blood stream infections (BSIs). Pediatric guidelines recommend monotherapy with an antipseudomonal beta-lactam or a carbapenem and to add a second anti-Gram-negative agent in selected situations. We evaluated the changes in the proportions of resistance of beta-lactam monotherapies vs.

Protocol for an embedded randomised controlled trial of Early versus Late Stopping of Antibiotics in children with Febrile Neutropenia (ELSA-FN).

In children with cancer, febrile neutropenia (FN) is one of the most common complications of treatment, a leading cause of unplanned and prolonged hospital admission and is the key driver of antibiotic exposure. Co-designed with key stakeholders, 'Early versus Late Stopping of Antibiotics in high-risk FN' (ELSA-FN) is a randomised controlled, non-inferiority trial that compares stopping antibiotics in clinically stable patients after 48 hours with the current standard of care, continuing antibiotics until absolute neutrophil recovery. As an Australian first, we will exploit the potential of electronic medical record (EMR) systems, embedding all key aspects of the trial including screening, consent, randomisation and data collection into standard clinical and EMR workflows.

Impact of time to antibiotics on clinical outcome in paediatric febrile neutropenia: a target trial emulation of 1685 episodes.

Background: Prompt antibiotic administration for febrile neutropenia (FN) is standard of care, and targets of time to antibiotics (TTA) <60 min are common. We sought to determine the effect of TTA ≥60 versus <60 min on adverse outcomes (intensive care unit (ICU) admission or death) in children with cancer and FN. Effect modification by a decision rule that predicts infection (AUS-rule) and bacteraemia were also investigated.

Crushed posaconazole delayed-release tablets for antifungal prophylaxis and treatment in children.

Objectives: Therapeutic drug monitoring (TDM) is recommended for posaconazole to achieve target concentrations of ≥0.7 mg/L and ≥1.0 mg/L for prophylaxis and treatment of invasive fungal infection (IFI), respectively.

The emergence of letermovir and maribavir drug-resistant mutations: from clinical trials to real-world studies.

Purpose Of Review: Cytomegalovirus (CMV) infection is associated with severe clinical disease and high morbidity in immunocompromised hosts. Letermovir and maribavir, are two recently developed antiviral drugs used in the prevention and treatment of resistant and refractory CMV. Following the publication of landmark randomized trials and increased use, both clinical trial data and real-world experience has reported the development of antiviral drug resistance.

Invasive fungal disease and antifungal prophylaxis in children with acute leukaemia: a multicentre retrospective Australian cohort study.

Background: Invasive fungal disease (IFD) is a significant complication for children receiving treatment for leukaemia, contributing to morbidity and mortality. Recent regional paediatric epidemiological IFD data are lacking. Additionally uncertainty remains regarding the optimal prophylactic approach in this context.

Biomarkers to predict and diagnose pulmonary complications in children post haematopoietic stem cell transplant.

Objectives: Haematopoietic cell transplant (HCT) is a cellular therapy for a group of high-risk children with cancer, immunodeficiency and metabolic disorders. Whilst curative for a child's underlying condition, HCT has significant risks associated, including lung injury. These complications are associated with increased post HCT mortality and require improved methods of risk stratification, diagnosis and treatment.

Pulmonary complications post allogeneic haematopoietic stem cell transplant in children.

Objectives: Haematopoietic stem cell transplant (HCT) is a cellular therapy that, whilst curative for a child's underlying disease, carries significant risk of mortality, including because of pulmonary complications. The aims of this study were to describe the burden of pulmonary complications post-HCT in a cohort of Australian children and identify risk factors for the development of these complications.

Methods: Patients were identified from the HCT databases at two paediatric transplant centres in Australia.

Challenges and considerations for antifungal prophylaxis in children with acute myeloid leukemia.

Introduction: Children receiving treatment for acute myeloid leukemia (AML) are at high risk of invasive fungal disease (IFD). Evidence from pediatric studies support the efficacy of antifungal prophylaxis in reducing the burden of IFD in children receiving therapy for AML, yet existing antifungal agents have specific limitations and comparative data to inform the optimal prophylactic approach are lacking.

Areas Covered: This review summarizes the epidemiology of invasive fungal disease (IFD) and current antifungal prophylaxis recommendations for children with acute myeloid leukemia (AML).

Opportunities and Barriers to Pediatric Antimicrobial Stewardship by Community Pharmacists.

Community Pharmacists (CPs) are easily accessible and can advocate for the appropriate use of antibiotics in children. Semi-structured interviews were conducted with 47 CPs and 46 parents/caregivers. Both groups expressed challenges to intervening when antibiotics have already been prescribed and highlighted the need for more support for CPs to make informed decisions.

Guideline for the management of infection in pediatric patients with cancer and hematopoietic cell transplantation recipients: 2024 update.

Our objective was to update a clinical practice guideline for the prevention and treatment of infection (CDI) in pediatric patients with cancer and hematopoietic cell transplantation recipients. We reconvened an international multi-disciplinary panel. A systematic review of randomized controlled trials (RCTs) for the prevention or treatment of CDI in any population was updated and identified 31 new RCTs.

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

Background: Neutropenic fever (NF) is a common complication in patients receiving chemotherapy. Judicious antimicrobial use is paramount to minimize morbidity and mortality and to avoid antimicrobial-related harms.

Objectives: To use an Australian national dataset of antimicrobial prescriptions for the treatment of NF to describe antimicrobial use, prescription guideline compliance and appropriateness; and to compare these findings across different healthcare settings and patient demographics.

Prospective External Validation of the Esbenshade Vanderbilt Models Accurately Predicts Bloodstream Infection Risk in Febrile Non-Neutropenic Children With Cancer.

Purpose: The optimal management of fever without severe neutropenia (absolute neutrophil count [ANC] ≥500/µL) in pediatric patients with cancer is undefined. The previously proposed Esbenshade Vanderbilt (EsVan) models accurately predict bacterial bloodstream infections (BSIs) in this population and provide risk stratification to aid management, but have lacked prospective external validation.

Materials And Methods: Episodes of fever with a central venous catheter and ANC ≥500/µL occurring in pediatric patients with cancer were prospectively collected from 18 academic medical centers.

Infections in children following chimeric antigen receptor T-cell therapy for B-cell acute lymphoblastic leukemia.

Background: CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy is transforming care for pediatric patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). There are limited pediatric-specific data concerning the infection risks associated with CD19 CAR-T therapy and the adequacy of current antimicrobial prophylaxis guidelines for these patients.

Methods: We describe the antimicrobial prophylaxis used and the types of infectious occurring in the first 100 days following CAR-T therapy for relapsed or refractory B-cell ALL in children and adolescents (≤18 years) at our centre.

Evaluating the accuracy and efficacy of an electronic medical record alert to identify paediatric patients with low-risk febrile neutropenia.

Background: Point-of-care decision support, embedded into electronic medical record (EMR) workflows, has the potential to improve efficiency, reduce unwarranted variation and improve patient outcomes. A clinical-facing best practice advisory (BPA) in the Epic EMR system was developed to identify children admitted with low-risk febrile neutropenia (FN) who should be considered for treatment at home after a brief inpatient stay. We evaluated the accuracy and impact of this BPA and identify areas for improvement.

An analysis of the resource use and costs of febrile neutropenia events in pediatric cancer patients in Australia.

Background: Febrile neutropenia (FN) in children with cancer generally requires in-hospital care, but low-risk patients may be successfully managed in an outpatient setting, potentially reducing the overall healthcare costs. Updated data on the costs of FN care are lacking.

Methods: A bottom-up microcosting analysis was conducted from the healthcare system perspective using data collected alongside the Australian PICNICC (Predicting Infectious Complications of Neutropenic sepsis In Children with Cancer) study.

The Challenge of Diagnosing Invasive Pulmonary Aspergillosis in Children: A Review of Existing and Emerging Tools.

Invasive pulmonary aspergillosis remains a major cause of morbidity and mortality for immunocompromised children, particularly for patients with acute leukaemia and those undergoing haematopoietic stem cell transplantation. Timely diagnosis, using a combination of computed tomography (CT) imaging and microbiological testing, is key to improve prognosis, yet there are inherent challenges in this process. For CT imaging, changes in children are generally less specific than those reported in adults and recent data are limited.