%0 Journal Article
%T Microdialysis as a safe and feasible method to study target-site piperacillin-tazobactam disposition in septic piglets and children.
%A Hermans E
%A Devreese M
%A Zeitlinger M
%A Dhont E
%A Verougstraete N
%A Colman R
%A Vande Walle J
%A De Paepe P
%A De Cock PA
%J Int J Antimicrob Agents
%V 62
%N 5
%D 2023 Nov 15
%M 37716576
%F 15.441
%R 10.1016/j.ijantimicag.2023.106970
%X OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.