Investigating Azithromycin Activity Against ESBL-Producing Escherichia coli Under Physiologically Relevant Conditions

Abstract

Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli are a major antimicrobial resistance threat. Although not standard therapy, azithromycin (AZM) displayed potent activity against ESBL E. coli in vitro, ex vivo, and in vivo. AZM demonstrated multi-fold reductions in MIC, bactericidal activity in supplemented mammalian tissue culture media, and enhanced dose-dependent activity with sodium bicarbonate (NaHCO3). AZM also augmented complement-mediated killing in human serum and improved survival by 50% in a murine bloodstream infection model. These findings underscore the need to revisit antibiotic susceptibility testing—incorporating host defense factors and NaHCO3—and suggest AZM merits further clinical evaluation for ESBL E. coli infections.