Carbapenem resistance in Pseudomonas aeruginosa

Abstract: Carbapenem (imipenem and meropenem) resistance in Pseudomonas aeruginosa is increasing, with global resistance rates approaching 20%. The most common resistance mechanisms are down-regulation of the porin OprD, and increased activity of multi-drug efflux pumps, primarily MexAB-OprM. Down-regulation of OprD, which is the primary porin for carbapenem uptake, confers resistance to both imipenem and meropenem, although the latter is affected less. Only meropenem is a substrate for the efflux pumps, due to the absence of a heterophilic side chain in the chemical structure of imipenem. Apart from alterations of OprD and the efflux pumps, changes of penicillin-binding proteins have been suggested as a third chromosomal mechanism of carbapenem resistance. Transferable carbapenemases, conferring resistance to all