Azithromycin resistance levels and mechanisms in Escherichia coli

AbstractDespite azithromycin being used in some countries to treat infections caused by Gram-negative pathogens, no resistance breakpoint forEscherichia coliexists. The aim of this study was to analyse the levels and mechanisms of azithromycin resistance inE. coli. The presence of chromosomal (rplD, rplVand23S rRNA) mutations, 10 macrolide resistance genes (MRGs) and efflux pump overexpression was determined in 343E. coliisolates. Overall, 89 (25.9%) isolates had MICs ≥ 32 mg/L to azithromycin, decreasing to 42 (12.2%) when assayed in the presence of Phe-Arg-β-Napthylamide, with 35 of these 42 possessing at least one MRG. Efflux pumps played a role in azithromycin resistance affecting the Minimal Inhibitory Concentration (MIC) levels of 91.2% isolates whereas chromosomal alterations seem to have a minimal role. At least one MRG was found in 22.7% of the isolates withmph(A) being the most commonly found gene. Themph(A) gene plays the main role in the development of azithromycin resistance and 93% of themph(A)-carrying isolates showed a MIC of 32 mg/L. In the absence of a specific resistance breakpoint our results suggest a MIC of 32 mg/L to be considered in order to detect isolates carrying mechanisms able to confer azithromycin resistance.