{Reference Type}: Journal Article
{Title}: Microdialysis as a safe and feasible method to study target-site piperacillin-tazobactam disposition in septic piglets and children.
{Author}: Hermans E;Devreese M;Zeitlinger M;Dhont E;Verougstraete N;Colman R;Vande Walle J;De Paepe P;De Cock PA;
{Journal}: Int J Antimicrob Agents
{Volume}: 62
{Issue}: 5
{Year}: 2023 Nov 15
{Factor}: 15.441
{DOI}: 10.1016/j.ijantimicag.2023.106970
{Abstract}: <B>OBJECTIVE: </B>Knowledge on the tissue penetration of piperacillin-tazobactam in children with sepsis is lacking. In this study, the feasibility and performance of microdialysis experiments were explored in septic piglets and children as part of a translational research project.<BR><B>METHODS: </B>Multiple-day microdialysis investigations were performed in muscle tissue of 22 piglets (of which 11 were septic) and 6 children with sepsis. An in vitro experiment preceded the (pre)clinical trials to derive optimal experimental settings and calibration technique. Linear mixed-effects models quantified the impact of sepsis on relative recovery (RR) and intercatheter, interindividual, interoccasion, and residual variability.<BR><B>RESULTS: </B>In vivo microdialysis was well tolerated in piglets and children, with no significant adverse events reported. Using identical experimental settings, lower RR values were recorded in healthy and septic piglets (range: piperacillin, 17.2-29.1% and tazobactam, 23.5-29.1%) compared with the in vitro experiment (piperacillin, 43.3% and tazobactam, 55.3%), and there were unacceptably low values in children with sepsis (<10%). As a result, methodological changes were made in the pediatric trial. Realistic tissue concentration-time curves were derived in piglets and children. In piglets, sepsis reduced the RR. The greatest contributors to RR variability were residual (>40%) and interoccasion (>30%) variability. The internal standard method was the preferred calibration technique in both piglets and children.<BR><B>CONCLUSIONS: </B>Microdialysis is a safe and applicable method for the measurement of tissue drug concentrations in piglets and children. This study demonstrated the impact of experimental settings, sepsis, and target population on individual RR.