Introduction Antibiotics are the cornerstone in the treatment of sepsis. Microdialysis (MD) data from adults suggest an impaired antibiotic tissue penetration in the case of sepsis. Tissue pharmacokinetics (PK) remain largely understudied in children. Juvenile pig models have proven to provide an accurate prediction of PK behavior in pediatric patients. This study aimed to investigate the influence of sepsis on antibiotic tissue penetration in a piglet model.

Methods In 17 piglets, piperacillin (PIP) - tazobactam (TAZ) was administered (75 mg/kg IV over 30 minutes, 6h dosing interval) over 4 days. Blood and MD samples (muscle) were collected in first-dose (FD) and steady-state (SS) conditions. In 11 piglets a continuous LPS infusion (36h) was administered to induce a septic state. In the 6 control animals (no LPS) time effects during the study period were evaluated. Non-compartmental PK analysis was used to determine the tissue penetration (AUC-ratio tissue/plasma). The AUC ratios were pairwise compared between the healthy and septic states in each piglet, data are reported as mean ± SD.

Results For PIP, the AUC ratio in FD conditions was significantly lower in the septic state (0.84 ± 0.22) compared to the healthy baseline measurement (1.06 ± 0.46) (P = 0.042). In SS conditions, comparable results were found with an AUC ratio of 1.09 ± 0.27 during baseline and 0.80 ± 0.22 in the septic state (p=0.009). The results for TAZ were similar to PIP. There were no time effects found in the control group.

Conclusion In this juvenile piglet model, sepsis impaired the PIP-TAZ tissue penetration. The results of this study warrant further research into the tissue PK of septic children to optimize the antibiotic dosing in this population.