Emergence of OXA-48-Producing Escherichia coli Clone ST38 in France

The blaOXA-48 gene encodes a carbapenem-hydrolyzing class D -lactamase that was first identified in Klebsiella pneumoniae from Turkey in 2003 and then extensively in that country (1, 11). There are few reports of blaOXA-48 in Escherichia coli, from Turkey, Israel, and Senegal (5, 6, 9). Furthermore, recent studies identified the spread of OXA-48-producers in North Africa (4, 12). E. coli NAA was recovered in November 2010 from rectal screening performed at the admission of a patient hospitalized at the Hôpital Européen Georges Pompidou, Paris, France. The patient was transferred from Egypt, where he had been hospitalized for pancreatic carcinoma and treated with ceftriaxone for salmonellosis. E. coli AME was recovered in December 2010 by rectal swab screening performed at the admission of a patient hospitalized in the intensive care unit of the Hôpital de Bicêtre in a suburb of Paris. That patient was living in France, but he had stayed in Egypt as a tourist during a 2-month period 4 months earlier (no hospitalization). The third E. coli isolate, GOG, was recovered in November 2010 by rectal swab screening performed at the admission of a patient hospitalized in the intensive care unit of the Hôpital Raymond-Poincaré (in a suburb of Paris). That patient was from Turkey, where he did not report any previous hospitalization. None of these patients had any hospitalizations in common in France. Susceptibility testing was performed by disk diffusion assay (Sanofi-Diagnostic Pasteur, Marnes-la-Coquette, France) (3). MICs were determined by Etest (AB bioMérieux; Solna, Sweden) on Mueller-Hinton agar plates at 37°C (3). All three E. coli isolates displayed an extended-spectrum -lactamase (ESBL) phenotype and exhibited the same pattern of antibiotic resistance, being resistant to all penicillins, resistant to cefotaxime, intermediately susceptible to aztreonam, and susceptible to ceftazidime (MIC of 0.5 g/ml) according to the updated CLSI guidelines (3). In addition, they showed reduced susceptibility to carbapenems. The MICs of imipenem, meropenem, and ertapenem were, respectively, 0.25, 0.25, and 0.5 g/ml for E. coli AME; 0.5, 0.25, and 1 g/ml for E. coli NAA; and 0.5, 0.25, and 2 g/ml for E. coli GOG. They were resistant to cotrimoxazole, sulfonamides, tobramycin, and gentamicin and susceptible to amikacin, chloramphenicol, tetracycline, tigecycline, and fluoroquinolones. The three isolates carried a blaCTX-M gene together with a blaTEM gene. Sequencing identified the -lactamases TEM-1 and CTX-M-24. CTX-M-24 is a point mutant derivative of CTX-M-14 that does not hydrolyze ceftazidime (7, 13). Mating-out assays performed as described previously (11) allowed us to obtain E. coli transconjugants coproducing the CTXM-24 and OXA-48 -lactamases, respectively. Plasmid analysis showed that these E. coli transconjugants harbored two plasmids (50 and 62 kb) encoding the ESBL and the class D -lactamase, respectively. In the three E. coli isolates, the blaOXA-48 plasmid was 62 kb in size and found positive for the repP gene (1), as reported for OXA-48-producing Klebsiella pneumoniae isolates recovered from different countries (previously estimated to be 70 kb in size but found to be 62 kb) (1). Phylogenetic grouping performed by PCR (2) showed that these E. coli isolates belonged to group D, corresponding to extraintestinal and pathogenic strains. Multilocus sequence typing performed as described previously (10) showed that all three E. coli isolates belonged to ST38. ST38 E. coli isolates had previously been identified in China (CTX-M-14 producer) (10) and Japan (CTX-M-9 and CTX-M-14 producers) (14). Pulsed-field gel electrophoresis analysis performed as described previously (1) showed that the three isolates were clonally related, indicating that the same clonal strain was circulating at least in Turkey and Egypt and was then imported into France. So far, dissemination of the OXA-48 resistance determinant was observed mainly in K. pneumoniae and to a lesser extent in Enterobacter cloacae (12). Consequently, OXA-48 producers have been observed only in hospital settings to date. We report here the spread of blaOXA-48 to the species E. coli isolated from a patient without a history of prior hospitalization. This indicates a dissemination of OXA-48-producing E. coli in the community, which gave rise to recurrent importation to France after the recent identification of an OXA-48-producing K. pneumoniae strain (8). We report here two cases with a clear link to Egypt, emphasizing that OXA-48 might be endemic to the African continent, in view of other reports from Senegal, Morocco, and Tunisia.