CT-004 - PIPERACILIN PHARMACOKINETICS AND TARGET ATTAINMENT IN PEDIATRIC LIVER TRANSPLANT RECIPIENTS.

R. Morales Junior^1,2, V. Juodinis^1,2, P. Romano³, N. Duarte³, D. Souza^1,2, S. Santos²; ¹Hospital Sírio-Libanês, São Paulo, SP, Brazil, ²University of São Paulo, São Paulo, SP, Brazil, ³Hospital das Clínicas, São Paulo, SP, Brazil.

Background: Pediatric liver transplant recipients are at high risk of infection, and frequently receive broad-spectrum antimicrobials such as piperacillin-tazobactam in the same doses prescribed in other critical conditions. Given that liver transplantation entails pathophysiological changes that impact drug disposition, our purpose is to characterize the pharmacokinetics (PK) and target attainment of piperacillin after transplantation.

Methods: Children ( < 18 years) with preserved renal function after liver transplantation receiving piperacillin/tazobactam were considered. The therapy started with the initial label-recommended dose of 100 mg/kg of piperacillin Q8H, infused over 30 minutes. Two blood samples were collected during the same dosing interval within 16 to 48 hours of starting antimicrobial. Total serum concentrations were determined by LC-MS/MS. The therapeutic target was defined as 100% of the time above the minimum inhibitory concentration (100%fT> MIC) of 16 mg/L for antipseudomonal activity. PK parameters were estimated using the one-compartment model with first-order kinetic equations. Data are presented as median and interquartile range.

Results: Eight patients with 16 measured piperacillin concentrations were included (median age 8 [6.8 – 16.5] months). The estimated piperacillin clearance, volume of distribution and half-life values were 1.9 (1.7–3.0) mL/kg/min, 0.24 (0.19–0.40) L/kg and 1.4 (1.1–1.5) hours, respectively. The estimated peak concentration was 253.7 (150.3-270.8) mg/L, while the trough was 5.4 (2.4–7.5) mg/L. The therapeutic target was achieved in 1 (12.5%) patient. No piperacillin-related adverse reactions were reported. A positive linear correlation between piperacillin clearance and age was observed (R²=0.8).

Conclusion: The label-recommended dose of piperacillin/tazobactam was insufficient to reach the target in most pediatric patients after liver transplantation. Older infants are at increased risk of subtherapeutic levels due to increase in elimination. To reduce unnecessary high peaks and improve target attainment, we suggest extending the infusion duration or increasing frequency of administration, and using therapy individualization strategies such as PK/PD-guided therapeutic drug monitoring and model-informed precision dosing.