Since the end of the last century resistance to oxyimino -lactams has steadily increased in Enterobacteriaceae. In the present work we studied extended-spectrum -lactamase (ESBL)-producing Enterobacteriaceae strains isolated in the teaching hospital of Clermont-Ferrand, France, between 2006 and 2009. A total of 1368 ESBL-producing isolates were collected. Most of these isolates (69%) were CTX-M-producing Escherichia coli. During the study, the clinical incidence increased by more than 400%, even in the emergency department, and especially in community-acquired infections, as is the case elsewhere in the world. Most of the ESBL-producing isolates remained susceptible to furans and fosfomycin, but only 50% to fluoroquinolons. In conclusion, ESBL-producing bacteria constantly increased during the study period. Unlike many studies, this increase was associated with the wide dissemination of three different CTX-M enzymes: CTX-M-14, CTX-M-15 and CTX-M-1.