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Imipenem, a highly active β-lactam antibiotic against Pseudomonas aeruginosa, has demonstrated a significantly decreased activity against strains identified at the Centre Hospitalier Universitaire de Sherbrooke (CHUS), over the past few years. A study on 252 clinical isolates, comparing the two carbapenems available in Canada, showed a superior in vitro activity of meropenem. Then, the lost or decrease resistance of OprD porins and the up regulation of the MexAB-OprM efflux pump, are the most important resistance mechanisms to these antibiotics. This porin is the unique way for imipenem to penetrate inside the bacterium, whereas meropenem can penetrate via other channels. The mutation inducing the loss of this porin induces a selective resistance to imipenem. The efflux pump affects only meropenem, but slightly. The two resistance mechanisms are thus needed to cause clinical resistance to meropenem. Hence, meropenem with its better in vitro activity and its lesser potential for resistance is the best carbapenem for the treatment of P. aeruginosa infections, even when the infection is caused by a fully imipenem susceptible strain. In microbiology laboratory assessments, one should give an interpretative reading of the antibiogram and depending on the observed phenotypes, make a deduction on the resistance mechanisms involved and an estimation of the mutation frequency inducing them. By doing so, the fight against bacterial resistance should be more efficient. [Copyright &y& Elsevier]