Precision Dosing of Beta-lactam Antibiotics in Critically Ill Children

The overall objective of this study is to investigate the impact of early model-informed precision dosing (MIPD) on target attainment of three beta-lactam antibiotics (amoxicillin-clavulanic acid, piperacillin-tazobactam and meropenem) in critically ill children. This evaluation includes a comparison with the more standard approach on clinical and patient-oriented measures.

Inclusion Criteria: * Subject aged between 0 - 17 years 10 months. * Subject admitted to a participating ward unit (Neonatal Intensive Care Unit, Pediatric Intensive Care Unit, Pediatric Hematology-Oncology unit). * Strongly suspected or confirmed systemic infection. * Subject planned to start on intravenous amoxicillin-clavulanic acid, piperacillin-tazobactam or meropenem treatment at least aimed for a minimum duration of two days at time of inclusion. If the subject was previously treated with the same beta-lactam, the minimum interval to the previous beta-lactam treatment episode is * 40 hours for amoxicillin-clavulanic acid (based on elimination half-life) * 8 hours for piperacillin-tazobactam and meropenem (based on elimination half-life) Subject planned to start on intravenous amoxicillin (without clavulanic acid) will not be included. * Informed consent/assent signed by parents or legal representatives of the subject. * Not previously enrolled in this trial. Exclusion Criteria: * Subject with serum creatinine level ≥ 2 mg/L at inclusion. * Subject receiving (or planned to receive) haemofiltration, extracorporeal membrane oxygenation, hemodialysis or peritoneal dialysis, molecular adsorbent recirculating system or any other exchange technique. * Subject receiving (or planned to receive) body cooling. * Subject death is deemed imminent and inevitable. * Reporting of first dosing advice (based on blood sampling) is not possible within 28 hours (\*) after start treatment. * The subject is known or suspected to be pregnant. * The subject has a known allergy to the specific beta-lactam antibiotic. (\*) The first (a posteriori) dose calculation and dose adjustment if necessary, is performed within a maximum timeframe of 28 hours after start of treatment (i.e. maximum timeframe to first dose adjustment).