Comprehensive stability analysis of 13 β-lactams and β-lactamase inhibitors in in vitro media, and novel supplement dosing strategy to mitigate thermal drug degradation.

ABSTRACT: Non-clinical antibiotic development relies on in vitro susceptibility and infection model studies. Validating the achievement of the targeted drug concentrations is essential to avoid under-estimation of drug effects and over-estimation of resistance emergence. While certain β-lactams (e.g., imipenem) and β-lactamase inhibitors (BLIs; clavulanic acid) are believed to be relatively unstable, limited tangible data on their stability in commonly used in vitro media are known. We aimed to determine the thermal stability of 10 β-lactams and 3 BLIs via LC-MS/MS in cation-adjusted Mueller Hinton broth at 25 and 36°C as well as agar at 4 and 37°C, and in water at -20, 4, and 25°C. Supplement dosing algorithms were developed to achieve broth concentrations close to their target over 2

SUBMITTER: Zhou J 

PROVIDER: S-EPMC10916406 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature