Repurposing Cefazolin-Avibactam for the Treatment of Drug Resistant Mycobacterium tuberculosis.

ABSTRACT: Background: While tuberculosis (TB) is curable and preventable, the most effective first-line antibiotics cannot kill multi-drug resistant (MDR) Mycobacterium tuberculosis (Mtb). Therefore, effective drugs are needed to combat MDR-TB, especially in children. Our objective was to repurpose cefazolin for MDR-TB treatment in children using principles of pharmacokinetic/pharmacodynamics (PK/PD). Methods: Cefazolin minimum inhibitory concentration (MIC) was identified in 17 clinical Mtb strains, with and without combination of the β-lactamase inhibitor, avibactam. Next, dose-ranging studies were performed using the intracellular hollow fiber model of TB (HFS-TB) to identify the optimal cefazolin exposure. Monte Carlo experiments were then performed in 10,000 c

SUBMITTER: Srivastava S 

PROVIDER: S-EPMC8569112 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature