P-1240. Precision in the Cradle: Evaluation of Cefepime Exposures in Neonates using Monte Carlo Simulations

TL;DR

This study evaluates cefepime dosing in neonates using simulations to find optimal regimens for different infection scenarios.

Contribution

The study introduces a simulation-based approach to determine optimal cefepime dosing regimens for term and preterm neonates based on MIC thresholds.

Findings

Term neonates require higher dosages and prolonged infusions to achieve optimal PTA at higher MICs.

Preterm neonates achieve sufficient PTA with lower dosages at lower MICs but need higher and more frequent dosing at higher MICs.

Abstract

Although cefepime (CFP) dosing has been evaluated in neonatal pharmacokinetic studies, variations in pharmacodynamic targets, patient characteristics, and sampling times across such studies make interpretation of findings challenging.

We aimed to identify CFP dosing regimens that achieved at least 90% probability of target attainment (PTA) in premature and term neonates. Population pharmacokinetic parameters were collected from four published studies and stratified by gestational age. The pharmacodynamic efficacy target was 70%fT >MIC. Monte Carlo simulations were performed to evaluate the PTA associated with four CFP dosing regimens, stratified by gestational age and weight. MICs of 2 and 8 mg/L were selected to reflect CLSI susceptibility breakpoints for Enterobacterales (< 2 mg/L) and P. aeruginosa (< 8 mg/L), with 4-8 mg/L representing the susceptible-dose dependent (SDD) range for Enterobacterales. Achievement of PTA ≥90% at these MICs was considered optimal.

PTAs for specific regimens and MICs are displayed in Table 1. In term neonates, CFP 50 mg/kg q12h (intermittent bolus [IB]) achieved 86% PTA at an MIC of 2 mg/L, while 50 mg/kg q8h (IB) and 50 mg/kg q8h with prolonged infusion (PI) achieved 95% and 100% PTA, respectively. At 8 mg/L, the same regimens achieved PTA rates of 65%, 88%, and 100%, respectively, indicating that prolonged infusion is particularly important when targeting higher MICs. In preterm neonates, CFP 30 mg/kg q12h (IB) achieved 99% PTA at an MIC of 2 mg/L and 85% at 8 mg/L. CFP 50 mg/kg q12h (IB) achieved 99% PTA at an MIC of 2 mg/L and 94% at 8 mg/L. Dosing at 50 mg/kg q8h (IB) achieved 100% PTA at an MIC of 2 mg/L and 99% at 8 mg/L.

Term neonates require higher CFP dosages (50 mg/kg/dose q8h) and prolonged infusions to achieve the pharmacodynamic target against a range of susceptible MICs. In preterm neonates, lower dosages (30 mg/kg/dose) achieved sufficient PTA only when the MIC was 2 mg/L; however, higher and more frequent dosing is necessary to achieve optimal PTA at an MIC of 8 mg/L. These findings are clinically relevant given the MIC susceptible breakpoint for Enterobacterales (<2 mg/L) and P. aeruginosa (<8 mg/L), with 4-8 mg/L representing the SDD category for Enterobacterales.

All Authors: No reported disclosures

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