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. Medical records were reviewed, and demographics, HCT characteristics and pulmonary complications documented. Relative risk ratio was used to identify risk factors for developing pulmonary complications prior to first transplant episode, and survival analysis performed to determine hazard ratio. Results: In total, 243 children underwent transplant during the study period, and pulmonary complications occurred in 48% (117/243) of children. Infectious complications were more common (55%) than non-infective complications (18%) and 26% of patients developed both. Risk factors for the development of pulmonary complications included the following: diagnoses of MPAL (RR 2.16, P = 0.02), matched unrelated donor (RR1.34, P = 0.03), peripheral blood (RR 1.36, P = 0.028) or cord blood (RR 1.73, P = 0.012) as the stem cell source and pre-existing lung disease (RR1.72, P < 0.0001). Children with a post-HCT lung complication had a significantly increased risk of mortality compared with those who did not (HR 3.9, P < 0.0001). Conclusion: This study demonstrates pulmonary complications continue to occur frequently in children post-HCT and contribute significantly to mortality. Highlighting the need for improved strategies to identify patients at risk pre-transplant and enhanced treatments for those who develop lung disease.

Evaluation of Pediatric HIV Postexposure Prophylaxis Guideline Following Child Sexual Assault in Western Australia.

BACKGROUND: HIV postexposure prophylaxis (PEP) following child sexual assault (CSA) is recommended in select cases. High rates of poor adherence to PEP are reported. We evaluated adherence to the recommended management of children following CSA at the tertiary pediatric facility in Western Australia and compared our approach with international guidelines. METHODS: Medical records were reviewed for all children <16 years old assessed at Perth Children's Hospital between October 1, 2016 and November 30, 2020 following alleged CSA. Data, including exposure type, PEP adherence and follow-up, were collected. A review of contemporary national and international PEP guidelines was undertaken in parallel. RESULTS: There were 511 alleged CSA events over the study period; 62/511 (12%) were appropriately risk-assessed as requiring PEP by the treating clinician. PEP was not prescribed in 8/62 (13%) events, with a reason documented for 6/8 (75%). Overall, less than half of children who were eligible for PEP were adherent to the 28-day regimen (23/54, 43%). Gastrointestinal upset contributed to early cessation in 5/54 (9%). Final 3-month blood-borne virus serology results were available in less than one in 3 children. A review of international clinical practice revealed significant heterogeneity of criteria for the provision of PEP and a paucity of pediatric-specific data. CONCLUSIONS: We identified several areas of our PEP management that required strengthening, with limited direction available in current international guidelines. We have adopted a broader use of fixed drug combinations and implemented a multifaceted follow-up program. It will be essential to review the impact of these changes.

The Impact of a Multifaceted Tertiary Pediatric Hospital's Antimicrobial Stewardship Service.

BACKGROUND: Antimicrobials are the most commonly prescribed drug class in children. Overuse through inappropriate prescribing is a key driver of antimicrobial resistance and is recognized as one of the top 10 threats to global health by the World Health Organization. METHODS: A prospective observational cohort study was performed following implementation of a multifaceted Antimicrobial Stewardship (AMS) program (January 2014 to December 2020). Data were collected on AMS and "handshake" ward rounds from patient information sources and directly from clinicians responsible for patient care. Primary outcomes include appropriateness of therapy (drug, dose, antimicrobial spectrum, duration and route), compliance with prescribing guidelines, antimicrobial expenditure, use of high-priority antimicrobials and duration of hospitalization. We compared outcomes across 3 time periods; January 2014-December 2015, January 2016-December 2017 and January 2018-December 2020. RESULTS: The appropriateness of individual antimicrobial orders improved across the study periods from 6111/7040 (79.4%) in the first 2 years following implementation of the AMS program to 17,819/19,229 (92.3%) in the latter period. Guideline compliance increased from 5426/7700 (70.5%) to 17,822/19,316 (92.3%). A reduction in overall antimicrobial expenditure (34% reduction, equivalent to $12.52 per bed day) and a decrease in antifungal expenditure (37% reduction, equivalent to $5.56 per bed day) was observed across the time periods. CONCLUSIONS: This study quantifies a comprehensive pediatric AMS program's sustained impact on reducing inappropriate antimicrobial use and expenditure and improving compliance with guidelines. The effectiveness of these interventions has been demonstrated and should be considered by institutions seeking to improve rational antimicrobial use in children.

Clinical experience with SUBA-itraconazole at a tertiary paediatric hospital.

BACKGROUND: Itraconazole remains a first-line antifungal agent for certain fungal infections in children, including allergic bronchopulmonary aspergillosis (ABPA) and sporotrichosis, but poor attainment of therapeutic drug levels is frequently observed with available oral formulations. A formulation of 'SUper BioAvailability itraconazole' (SUBA-itraconazole; Lozanoc®) has been developed, with adult studies demonstrating rapid and reliable attainment of therapeutic levels, yet paediatric data are lacking. OBJECTIVES: To assess the safety, efficacy and attainment of therapeutic drug levels of the SUBA-itraconazole formulation in children. METHODS: A single-centre retrospective cohort study was conducted, including all patients prescribed SUBA-itraconazole from May 2018 to February 2020. The recommended initial treatment dose was 5 mg/kg twice daily (to a maximum of 400 mg/day) rounded to the nearest capsule size and 2.5 mg/kg/day for prophylaxis. RESULTS: Nineteen patients received SUBA-itraconazole and the median age was 12 years. The median dose was 8.5 mg/kg/day and the median duration was 6 weeks. Indications included ABPA (16 patients), sporotrichosis (1), cutaneous fungal infection (1) and prophylaxis (1). Of patients with serum levels measured, almost 60% (10/17) achieved a therapeutic level, 3 with one dose adjustment and 7 following the initial dose. Adherence to dose-adjustment recommendations amongst the seven patients not achieving therapeutic levels was poor. Of patients with ABPA, 13/16 (81%) demonstrated a therapeutic response in IgE level. SUBA-itraconazole was well tolerated with no cessations related to adverse effects. CONCLUSIONS: SUBA-itraconazole is well tolerated in children, with rapid attainment of therapeutic levels in the majority of patients, and may represent a superior formulation for children in whom itraconazole is indicated for treatment or prevention of fungal infection.