Time Above all Else: Pharmacodynamic Analysis of β-Lactams in Critically Ill Patients.

β-lactams are the most commonly utilized antibiotics in intensive care units (ICUs). As critically ill patients often experience pharmacokinetic aberrations, and rates of antimicrobial resistance vary between hospital settings, reliance on tertiary sources or package labeling to guide empiric dosing often results in suboptimal β-lactam exposure. The primary objective was to identify β-lactam regimens capable of achieving ≥90% cumulative fraction of response (CFR) against seven Gram-negative pathogens within four ICUs at our institution. Unit-specific MIC distribution data was utilized in combination with published pharmacokinetic parameters in critically ill patients to perform Monte Carlo simulations. The percentage of time for which the unbound concentration of antibiotic remained above the MIC (%ƒT>MIC) was utilized as the pharmacodynamic target: 70%ƒT>MIC for cefepime, 40%ƒT>MIC for meropenem, and 50%ƒT>MIC for piperacillin/tazobactam. Regimens were modeled to determine the likelihood of achieving ≥90% CFR. Overall, intermittently dosed cefepime, meropenem, and piperacillin/tazobactam failed to achieve ≥90% CFR for every organism. Cefepime 2g IB q8h failed to achieve ≥90% CFR for K. pneumoniae or E. cloacae despite susceptibility rates exceeding 90%. Piperacillin/tazobactam 4.5g PI q6h achieved <85% CFR for P. aeruginosa and <50% CFR for A. baumannii in every ICU. Meropenem 2g PI q8h and meropenem 2g PI q6h were the only regimens capable of achieving ≥90% CFR for P. aeruginosa in all units. Utilization of Monte Carlo simulations, with incorporation of local MIC distribution data, provides a mechanism to effectively predict optimal agent and dose selection within specific hospital systems, thereby enhancing PK/PD optimization and improving clinical efficacy. This article is protected by copyright. All rights reserved.