PD Dr. med. habil. Julia Anna Bielicki

Research Project  | 4 Project Members

We will develop and validate approaches for sentinel One Health AMR surveillance in rural sub-Saharan Africa. Building on previous novel work showing that metagenomic profiling of pooled faecal material can accurately predict AMR prevalence in clinical isolates of Enterobacterales, we aim to extend this work to other bacterial species and One Health compartments. We will conduct metagenomic profiling on pooled DNA extracts from human stool samples (hospital and community-level) and from household environments in Burkina Faso and Kenya. We will assemble existing local data from hospital-based microbiology diagnostic laboratories. We will perform community-level surveys and use randomly selected households within village clusters. We will sample suspected environmental AMR exposure sites in and around households and collect data on community-level human and animal antibiotic use, hygiene practices, contact with domestic animals, and sanitary facilities. Data analysis will seek to quantify community-level exposure risks and evaluate the accuracy of predicting resistance in clinical isolates using metagenomic data. A cost-utility analysis will determine under what circumstances the use of pooled metagenomic data to inform empirical antibiotic policies would represent an efficient use of resources.The proposed work will establish how this approach could provide a viable, low-cost and convenient approach for AMR sentinel surveillance in settings which - like many in rural sub-Saharan Africa - lack systematic microbiological diagnostics and where sewage systems are non-existing.

Research Project  | 4 Project Members

Nearly 1 in 10 newborns in Europe is admitted to a neonatal intensive care unit (NICU) in the first days of life, around 400,000 admissions every year. While care in a neonatal unit results in a greater chance of survival in newborns with serious illness, it also increases the risk of exposure to bacteria from the hospital environment. These can cause serious infections in babies, which are commonly resistant to many routinely used antibiotics.

Premature babies are a particularly vulnerable population, because their immune system is immature, and their skin and mucosa are not yet effective barriers against infections. Those who are seriously ill need life saving devices and prolonged antibiotic treatments. All of these factors increase the risk of being colonized with antibiotic-resistant organisms. Colonisation with resistant bacteria is a major problem for several reasons: the colonised babies are at higher risk of severe infection, but they are also a source of resistant bacteria being introduced to the hospital environment, which can potentially infect other babies in the unit.

NeoIPC is establishing innovative approaches for optimal infection prevention of resistant bacteria in NICUs by integrating clinical research, implementation science and surveillance.

Research Project  | 1 Project Members

VERDI is a project aiming to describe the impact of variants of concern and the role of children in the transmission of SARS-CoV-2, in their homes and schools, how the infection impacts clinical disease in children and adverse pregnancy outcomes, and treatment. The project will also investigate vaccine strategies in children and pregnant women on disease and transmission in the face of new VoC. This evidence will allow us to rapidly deliver recommendations on the best strategies to control viral spread in paediatric populations, as well as on optimized clinical management and treatment of COVID-19 children and pregnant women.

Research Project  | 4 Project Members

The project will build the SwissPharmacoKinetics clinical data warehouse SwissPK cdw , with encoded clinical, pharmacokinetic, physiological and genetic data from Swiss Children's Hospitals (real-world data). Within the project the collaborating groups will focus on the patients with highest need for optimised dosage regimens, namely the paediatric patients, and will include a pre-defined list of 1-3 drugs. The long-term goal beyond the funding period is to establish a dynamic, steadily growing CDW for any drug and any patient cohort. It is aim to significantly extend based on analytical evidence the current expert-opinio-only recommendations for drug dosage in paediatrics and to identify covariates which best predict the pharmacokinetics in children, including physiological factors, genetic polymorphisms in ADMET-relevant genes, disease-related factors and co-medication.

Research Project  | 3 Project Members

Community-acquired pneumonia (CAP) is a common reason for hospitalisation in childhood and represents a considerable socioeconomic burden. In hospitalised adults with CAP, we have shown a beneficial effect of short-term steroid treatment on time to clinical stability and on duration of hospital stay in a randomised controlled trial (RCT). These benefits in adults with CAP have been confirmed in a recent meta-analysis and appear to be independent of the aetiology of CAP. It is unclear if adjunct steroid treatment benefits children with CAP.Rationale: An intervention that shortens time to stability and discharge in childhood CAP would carry substantial socioeconomic benefits in terms of healthcare resource utilization as well as parental and child absenteeism from work and out-of-home activities, respectively. Based on our findings in adult patients with CAP, we expect a positive clinical effect of steroids also in children. So far, no large-scale RCTs have evaluated the effectiveness of oral steroids on patient-relevant or clinically relevant endpoints in childhood CAP. In particular, it is unclear whether clinical improvement in the short-term is offset by a mid-term increase in CAP recurrence. Aim of the study: The overall aim of the trial is to evaluate the impact of oral steroid treatment in children with CAP on outcomes that are of high importance for patients. Specifically, we aim to concurrently assess the effect of adjunct oral steroids in children hospitalised for CAP on clinical stability (efficacy) and CAP recurrence (safety).Objectives: The primary objective is to concurrently evaluate (i) whether treatment of children hospitalised for CAP with oral betamethasone is superior to placebo for clinical stability (defined as resolution of vital sign abnormalities in room air) within 48 hours of hospitalization; (ii) whether treatment of children hospitalised for CAP with oral betamethasone is noninferior to placebo for CAP-related readmissions to hospital within 28 days of randomisation. Other objectives include the evaluation of effects of oral betamethasone treatment (versus placebo) in children hospitalised for CAP on: duration of hospital stay; severity and duration of CAP symptoms; parental absence from work and/or child absence from routine out-of-home care or school; overall duration of antibiotic exposure and inpatient days; intensive care unit admissions; mortality; rate and severity of solicited clinical side effects and serious adverse events. Exploratory subgroup analyses are planned to evaluate the effect of age, initial antibiotic treatment, respiratory pathogen detected in initial nasopharyngeal swab and radiological evidence of CAP. Study Design: We propose a pragmatic randomised, controlled, patient-, care-giver-, investigator- and outcome-assessor blinded multicentre trial in 8 Swiss paediatric departments with two parallel groups (one active, one control; 1:1 ratio). Preschool and school-age children with moderate to severe CAP (defined clinically) requiring admission to hospital will be included. 700 patients will be randomised 1:1 to receive betamethasone (Betnesol®) (active group: 0.2 mg/kg/d in 1 daily dose for 2 days; control group: 2 days of placebo). The co-primary endpoints will be (i) the proportion of children who are clinically stable within 48 hours of randomisation; the proportion of children requiring CAP-related readmission to hospital within 28 days of randomisation. Significance: Any treatment associated with an increased likelihood of early clinical stability may lead to a higher proportion of children suitable for prompt discharge, in turn reducing the patient-relevant outcome of length of stay. This would likely lead to changes in paediatric CAP management in Switzerland (and similar high-income settings), especially if recurrence of moderate-severe CAP remained demonstrably low.