With a reported incidence up to 24%, postoperative infections present a significant complication in neonates and children who undergo surgical correction of congenital heart disease [1,2]. The temporarily immunosuppressive state induced by cardiopulmonary bypass in combination with extensive tissue injury and intensive care treatment modalities leaves children vulnerable to sternal wound infections, pneumonia and bloodstream infections in the early recovery phase after cardiac surgery. These infections contribute to prolonged hospital length of stay, increased morbidity and mortality, and higher medical expenses [1,3].

Targeting both Gram-positive and Gram-negative pathogens with relatively low toxicity, amoxicillin-clavulanate is a first choice antibiotic in postoperative infections [4]. Nevertheless, amoxicillin-clavulanate pharmacokinetics (PK) have not previously been studied in infants and children after cardiac surgery. In addition to their specific developmental and maturational characteristics, these patients encounter significant pathophysiological and surgery-induced alterations such as inflammation, fluid overload, low cardiac output syndrome, and impaired kidney function, which might affect drug PK [5]. This potentially results in a highly variable antibiotic exposure with standard dosing guidelines in children after cardiac surgery [6,7].

For β-lactams that exhibit time-dependent antibiotic activity, adequate exposure requires sufficient time that unbound drug plasma concentration is above the MIC of common pathogens (fT>MIC). The optimal β-lactam therapeutic target in critically ill children is not consensually defined and ranges from 40%fT>MIC to 100%fT>6×MIC, with reported evidence of therapeutic failure with the lower PK/pharmacodynamic (PK/PD) targets in less susceptible pathogens advocating to aim for more stringent PK/PD targets in pediatric intensive care unit (PICU) patients to ensure bacterial eradication and clinical cure [6,[8], [9], [10]].

Improved understanding of amoxicillin-clavulanate disposition in critically ill children after cardiac surgery may lead to optimisation of antibiotic treatment in this vulnerable population, including neonates. The aim of this study was: (i) to investigate the PK of intravenously administered amoxicillin-clavulanate in children shortly after cardiac surgery; (ii) identify predictors of interpatient PK variability; and (iii) develop optimised amoxicillin-clavulanate dosing recommendations for this population based on PK/PD target attainment evaluation.