We analyzed 43 CTX-M-15–producing Escherichia coli isolates and 6 plasmids encoding the blaCTX-M-15 gene from Canada, India, Kuwait, France, Switzerland, Portugal, and Spain. Most isolates belonged to phylogroups B2 (50%) and D (25%). An EC-B2 strain of clonal complex sequence type (ST) 131 was detected in all countries; other B2 isolates corresponded to ST28, ST405, ST354, and ST695 from specific areas. EC-D strains were clonally unrelated but isolates from 3 countries belonged to ST405. All CTX-M-15 plasmids corresponded to IncFII group with overrepresentation of 3 HpaI-digested plasmid DNA profiles (A, B and C; 85–120kb, similarity >70%). Plasmid A was detected in EC-B2 strains (ST131, ST354, or ST405), plasmid C was detected in B2 and D strains, and plasmid B was confined to worldwide-disseminated ST131. Most plasmids contained blaOXA-1, aac(6′)-Ib-cr, and blaTEM-1. Worldwide dissemination of CTX-M-15 seems to be determined by clonal complexes ST131 and ST405 and multidrug-resistant IncFII plasmids.

Extended-spectrum β-lactamases (ESBLs) represent a major threat among multidrug-resistant bacterial isolates. They have been increasingly described worldwide since their description in the early 1980s and have risen to prominence among Enterobacteriaceae isolates in nearly all European countries, now not only in the nosocomial but also in the community setting [ 1 x 1 Paterson, DL and Bonomo, RA. Extended-spectrum β-lactamases: a clinical update. Clin Microbiol Rev. 2005; 18: 657–686 Crossref | PubMed | Scopus (1833) | Google Scholar See all References , 2 x 2 Cantón, R and Coque, TM. The CTX-M β-lactamase pandemic. Curr Opin Microbiol. 2006; 9: 466–475 Crossref | PubMed | Scopus (665) | Google Scholar See all References , 3 x 3 Livermore, DM, Canton, R, Gniadkowski, M et al. CTX-M: changing the face of ESBLs in Europe. J Antimicrob Chemother. 2007; 59: 165–174 Crossref | PubMed | Scopus (614) | Google Scholar See all References ]. This review focuses on current European ESBL epidemiology. The population structure of ESBL-producing isolates and the nature of mobile genetic elements carrying bla_ESBL genes are analysed.

The spread of extended-spectrum-β-lactamase (ESBL)-producing organisms, particularly those harboring the CTX-M-type enzymes, both in the hospital and in the community, is difficult to discontinue due to the successful mobilization and evolution of the genetic elements harboring ESBL genes and coresistance rates in these isolates. The activities of tigecycline against 285 non-clonally related isolates (172 from Escherichia coli , 84 from Klebsiella spp., 20 from Enterobacter spp., 5 from Salmonella spp., and 4 from Citrobacter spp.) expressing well-characterized ESBLs and recovered in our hospital and its community area of influence were comparatively assessed (CLSI microdilution). Susceptibility rates for meropenem, imipenem, tigecycline, amikacin, and piperacillin-tazobactam were 100%, 100%, 97.5%, 93.3%, and 93%, respectively. Tigecycline (mode MIC, 0.5 μg/ml; MIC ₉₀ , 1 μg/ml) was 4- to 256-fold more active than doxycycline and minocycline (mode MIC range, 2 to 128 μg/ml). CTX-Ms were the most frequent ESBLs (61.4%), 65.8% in community and 58.6% in nosocomial isolates. CTX-M-9 (22%), CTX-M-14 (15.8%), and CTX-M-10 (14%) were the most represented derivatives. SHV and TEM variants constituted 22.8% and 15.8% of the ESBLs, respectively. Overall coresistance rates were as follows: gentamicin, 27.4%; tobramycin, 27.4%; amikacin, 6.7%; and chloramphenicol, 29.1%. Sulfonamide (61.7%), trimethoprim (52.3%), streptomycin (50.5%), and ciprofloxacin (37.2%) resistance levels were significantly ( P < 0.001) associated with CTX-M-9 producers. No tigecycline resistance was observed, although seven Klebsiella pneumoniae isolates exhibited intermediate MICs (4 μg/ml). Tigecycline, lacking cross-resistance with other compounds, could represent an opportunity to reduce the intensity of selection for ESBL-producing organisms derived from the use of other antimicrobial agents. However, this in vitro promise requires support from clinical studies.