E. coli and Macrolide Resistance | CDC EID

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Volume 15, Number 10–October 2009
Dispatch
Escherichia coli as Reservoir for Macrolide Resistance Genes
Minh Chau Phuc Nguyen, Paul-Louis Woerther, Mathilde Bouvet, Antoine Andremont, Roland Leclercq, and Annie Canu
Author affiliations: Université de Caen, Caen, France (M.C.P. Nguyen, M. Bouvet, R. Leclercq, A. Canu); and University Paris-Diderot Medical School, Paris, France (P.-L. Woerther, A. Andremont)

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Abstract
The plasmid-borne mph(A) gene that confers resistance to azithromycin and has recently emerged in Shigella sonnei is present in multidrug- and non–multidrug-resistant Escherichia coli isolates from 4 continents. Further spread of mph(A) to Shigella and Salmonella spp. may be expected.

Macrolides have been regarded for many decades as having good activity and safety for the treatment of infections caused by gram-positive cocci. In general, macrolides show modest potency against Enterobacteriaceae. Most Shigella and Salmonella spp. pathogens display MICs of azithromycin, a macrolide antimicrobial drug, ranging from 2 mg/L to 8 mg/L (1). Despite these relatively high MICs, azithromycin is an attractive option for several reasons. It can be given once a day and attains high intracellular concentrations and sufficient concentrations in the colon of patients to inhibit Shigella and Salmonella spp. Azithromycin is recommended by the American Academy of Pediatrics for treatment of shigellosis in children (2) and by the World Health Organization as a second-line treatment for adults (3). It has also been proposed for short-course treatment of typhoid fever (4).

We recently reported an outbreak of shigellosis in Paris, France; failure of azithromycin treatment was related to emergence of plasmid-mediated resistance to macrolides (5). Resistance was related to the expression of a macrolide 2´ phosphotransferase encoded by the mph(A) gene. Because shigellosis remains a common gastrointestinal disease in both developing and industrialized countries, emergence of macrolide resistance may have major public health consequences.

Since the early reports by Ochiai (6) and Akiba (7) at the end of the 1950s, plasmid-mediated transfer of resistance genes between Escherichia coli and Shigella spp. has been reported in several instances (8). Therefore, we hypothesized that E. coli might constitute a major reservoir for macrolide resistance genes that could be subsequently transferred to Shigella sonnei.

Acquired resistance to macrolides may result from a variety of mechanisms of resistance, several of which have already been reported in Enterobacteriaceae (9,10). These mechanisms include target site modification by methylases encoded by erm genes, in particular erm(A), erm(B), and erm(C). Macrolides may be inactivated by modifying enzymes first reported in Enterobacteriaceae (11,12), e.g., esterases encoded by ere(A) or ere(B) genes or phosphotransferases encoded by mph(A), mph(B), and mph(D) genes. The third mechanism is acquisition of efflux pumps, mef(A) and msr(A), that have been found essentially in gram-positive organisms, although mef(A) has been identified in gram-negative organisms (10). All of these genes confer full cross-resistance between erythromycin and azithromycin (9). We aimed to assess the prevalence of acquired resistance to macrolides in commensal and clinical isolates of E. coli from various geographic origins and to characterize the mechanisms underlying E. coli resistance to macrolides.

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