Gepotidacin Pharmacokinetics-Pharmacodynamics against Escherichia coli in the One-Compartment and Hollow-Fiber <i>In Vitro</i> Infection Model Systems
Brian D. VanScoy, Elizabeth A. Lakota, Haley Conde, Steven Fikes, Sujata M. Bhavnani, Philippa B. Elefante, Nicole E. Scangarella-Oman, Paul G. Ambrose
Abstract
Gepotidacin is a novel, first-in-class triazaacenaphthylene antibiotic that inhibits bacterial DNA replication by a distinct mechanism of action with an in vitro spectrum of activity that includes Escherichia coli . Our objectives here were the following: (i) to identify the pharmacokinetics-pharmacodynamics (PK-PD) index associated with efficacy for gepotidacin against E. coli ; (ii) to determine the magnitude of the above-described PK-PD index associated with various bacterial reduction endpoints for E. coli ; and (iii) to characterize the relationship between gepotidacin exposure and on-therapy E. coli resistance amplification.