Molecular Epidemiology and Mechanisms of Carbapenem Resistance in Pseudomonas aeruginosa

Antimicrob Agents Chemother 53(11):4783-4788 (2009) PMID 19738025 PMCID PMC2772299

The contribution of different mechanisms of resistance to carbapenems was investigated among a collection of imipenem and meropenem non-susceptible Pseudomonas aeruginosa isolates. This screening included the recently reported extended-spectrum cephalosporinases (ESACs) hydrolyzing weakly carbapenems. Eighty-seven per cent of the studied isolates were resistant to imipenem. Genes encoding metallo-beta-lactamases or carbapenem-hydrolyzing oxacillinases were not identified. The main mechanism associated with imipenem resistance was the loss of outer membrane protein OprD. Identification of overexpressed ESACs and loss of OprD was observed for 65% of the isolates, all being fully resistant to imipenem. Resistance to meropenem was observed in 78% of the isolates, all but one being also resistant to imipenem. Overexpression of the MexAB-OprM, MexXY-OprM or MexCD-OprJ efflux systems were observed in 60% of the isolates, suggesting the contribution of efflux mechanisms in resistance to meropenem. The loss of porin OprD and ESAC overproduction was observed in 100% and 92% of the meropenem resistant isolates, respectively. P. aeruginosa can very often accumulate different resistance mechanisms, including ESAC production, leading to carbapenem resistance.