PII-117 - PIPERACILLINE PHARMACOKINETICS AND PHARMACODYNAMICS IN PEDIATRIC PATIENTS WHO RECEIVED HIGH FREQUENCY PIPERACILLIN/TAZOBACTAM DOSING DURING SURGERY.

C. McIntire, J. Luna Torres, P. Tang, J. Kaplan, A. Vinks, S. Tang Girdwood; Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

Background: A study in adults found that piperacillin/tazobactam (PTZ), a broad-spectrum antibiotic, dosed every 4 hours (q4h) intra-operatively (intra-op) was inadequate (1). PK/PD of high frequency q2h dosing has not been studied despite risk of PTZ-associated acute kidney injury (AKI). We compared q2h intra-op and q6h post-op PK/PD parameters and hypothesized PK parameters and PTZ exposure would be different due to intra-op physiologic changes.

Methods: Pediatric patients who received PTZ during complex abdominal surgery or transplants and who had intra-op and post-op opportunistic samples were included. Using a published PK model (2) and observed concentrations, individual piperacillin (PIP) PK/PD parameters were estimated using Bayesian estimation.

Results: Thirteen patients were included (median age: 3.1 years, 23% male, 85% liver transplant). PK parameters were not significantly different (Table) but at an individual level, intra-op to post-op clearance and central volume ratios varied between 0.5 – 2-fold. Intra-op PIP exposures were higher and intra-op target attainment occurred more frequently.

Conclusion: PIP exposures were significantly higher intra-op due to high frequency dosing in the setting of similar PK parameters between the two states. These higher exposures may increase risk of PTZ-AKI and q2h dosing intra-op warrants further evaluation.

1. Dupon M, Janvier G, Vincon G, Winnock S, Demote-Mainard F, Capeyron O et al. Plasma levels of piperacillin and vancomycin used as prophylaxis in liver transplant patients. Eur J Clin Pharmacol. 1993;45(6):529-534.

2. De Cock P, van Dijkman SC, de Jaeger A, Willems J, Carlier M, Verstraete A, et al. Dose optimization of piperacillin/tazobactam in critically ill children. J Antimicrob Chemother. 2017;72(7):2002-2011.

Table 1: PK/PD parameters in the intra-op and post-op state. We evaluated two PD targets: time free concentrations were above the minimum inhibitory concentration (MIC) for 100% of the dosing interval and 4x MIC for 100% of the dosing interval. For MIC, we used the Clinical Laboratory Standard Institute breakpoint for Enterococcus (8 mg/L), one of the most common cause of infections in patients who undergo abdominal surgeries. Student t-test was used for normally distributed continuous data and Wilcoxon Sign Rank test was used for non-normally distributed continuous data. McNemar’s test was used for categorical data. *p-value could not be calculated since 100% of patients in intra-op period met target.