P-1173. Analysis of MIC and Disk Diffusion Testing Variables for Gepotidacin and Levofloxacin against Gram-Positive and Gram-Negative Isolates
Abstract
Abstract Background Gepotidacin is a novel, bactericidal, first-in-class triazaacenaphthylene antibacterial that selectively inhibits bacterial replication through a distinct binding site, unique mechanism of action and, for most target pathogens, well-balanced inhibition of two Type II topoisomerase enzymes (DNA gyrase and topoisomerase IV). Gepotidacin was recently approved by the FDA for the treatment of uncomplicated urinary tract infections (uUTI). This study evaluated the effects of several antimicrobial susceptibility testing (AST) variables on standardized (i.e., CLSI, EUCAST) testing methods for key uUTI uropathogens. Variables shown to significantly impact gepotidacin BMD MICs and/or DD zone for Enterobacterales Methods The in vitro activity of gepotidacin and levofloxacin was evaluated using 4 CLSI AST methods: broth microdilution (BMD), broth macrodilution (MD), agar dilution (AD) and disk diffusion (DD). 85 clinical isolates were included for MIC testing and 90 isolates for DD, including E. faecalis (EF), S. saprophyticus (SS), and several Enterobacterales species known to be implicated in uUTI. Variables (BMD and DD only) including but not limited to inoculum concentration, temperature, atmospheric conditions, pH, and urine were tested. Results Gepotidacin mean reference BMD MICs varied no more than 1 dilution over multiple days, for all species tested. MICs were comparable between the 3 MIC testing methods with MICs for 84 of 85 isolates within ± 1 dilution.…
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