Abstract:
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Despite azithromycin being used in some countries to
treat infections caused by Gram-negative pathogens, no
resistance breakpoint for Escherichia coli exists. The aim of
this study was to analyse the levels and mechanisms of
azithromycin resistance in E. coli. The presence of chromosomal
(rplD, rplV and 23S rRNA) mutations, 10 macrolide resistance
genes (MRGs) and efflux pump overexpression was determined in
343 E. coli isolates. Overall, 89 (25.9%) isolates had
MICs\xE2\x80\x89\xE2\x89\xA5\xE2\x80\x8932\xE2\x80\x89mg/L to
azithromycin, decreasing to 42 (12.2%) when assayed in the
presence of Phe-Arg-\xCE\xB2-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 with mph(A) being the most
commonly found gene. The mph(A) gene plays the main role in the
development of azithromycin resistance and 93% of the
mph(A)-carrying isolates showed a MIC of 32\xE2\x80\x89mg/L. In
the absence of a specific resistance breakpoint our results
suggest a MIC of 32\xE2\x80\x89mg/L to be considered in order to
detect isolates carrying mechanisms able to confer azithromycin
resistance. |