Carbapenems are last resort b-lactams drugs to treat infections caused by multidrug resistant Gram-negative bacteria and the worldwide dissemination of carbapenem resistant enterobacteriaceae is a major public health concern. Among enterobacteriaceae, Escherichia coli is the leading cause of infections both in the hospital and in the community. About half of the CP-Ec strains from the French National Reference Centre belong to few MLST types (ST38, ST167, ST10 and ST410) (Gauthier et al. 2018). However, despite the threat that represents the dissemination of carbapenemase producing E. coli (CP-Ec) in the community, the genetic bases sustaining their selection and their expansion remain unknown. We have addressed this issue by combining evolutionary genomics and functional analysis on CP-Ec isolates. In particular we showed that the acquisition of mutated ftsI and of a specific ompC allele by recombination, and recurrent mutations inactivating ompF or reducing its expression are common features of CP-Ec isolates, in particular of disseminated clones. The order of the genetic events indicated that carbapenemase genes are preferentially acquired by strains first muted in these genes contributing to b-lactams resistance. Furthermore, antibiotic susceptibility testing of isolates with different genotypes led us to propose that fixation of carbapenemase genes in disseminated clones might be triggered mainly by other b-lactams than carbapenems.