Evaluation of the need for dosing adaptations in obese patients for surgical antibiotic prophylaxis: a model-based analysis of cefazolin pharmacokinetics

• DOI: 10.1016/j.bja.2024.11.044
• Publication Date: 2025-02-01T04:23:00Z
• Authors: Davide Bindellini; Philipp Simon; David Busse; Robin Michelet; David Petroff; Linda B.S. Aulin; Christoph Dorn; Markus Zeitlinger; Wilhelm Huisinga; Hermann Wrigge; Charlotte Kloft
• Keywords: Cefazolin; Pharmacodynamics

Cefazolin is used as a prophylactic antibiotic to reduce surgical site infections (SSIs). Obesity has been identified risk factor for SSIs. dosing recommendations and guidelines are currently inconsistent obese patients. As plasma target-site exposure might differ, pharmacokinetic data from the sites of SSIs essential evaluate treatment efficacy: these can be obtained via tissue microdialysis. This analysis was designed need adaptations in patients prophylaxis. Data 15 (BMImedian = 52.6 kg m-2) age- sex-matched nonobese 26.0 who received 2 g cefazolin i.v. infusion infection prophylaxis were included analysis. Pharmacokinetic interstitial space fluid (ISF) adipose analysed simultaneously using nonlinear mixed-effects modelling. Dosing regimens evaluated by calculating probability target attainment (PTA) cumulative fraction response (CFR) ISF unbound concentration above minimum inhibitory 100% time (fT>MIC 100%). considered adequate when PTA CFR ≥90%. Evaluation doses 1 with redosing at either 3 or 4 h found most suitable regimen both (PTA >90% both). model-based analysis, fT>MIC target, showed that not required