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 â-lactams except aztreonam, have emerged during the last decade, and consist of five groups of enzymes, namely IMP, VIM, SPM, GIM and SIM. These enzymes are designated metallo-â-lactamases (MBL) due to their dependency of zinc for â-lactam hydrolysis. The genes encoding the MBLs are usually found on integrons, often embedded in functional transposons. The aim of this thesis was to study chromosomal and transferable carbapenemresistance in clinical isolates of P. aeruginosa. Totally 67 isolates with variable levels of carbapenem resistance were characterized regarding transcription of the chromosomal genes encoding OprD, and the efflux pumps MexAB-OprM, MexXY, MexCD-OprJ and MexEFOprN. Transcription of the genes encoding penicillin-binding 2 and 3 (PBP-2 and -3) was studied in some of the isolates. Quantitative reverse transcriptase PCR (qRT-PCR) was used for the quantification of mRNA for the respective resistance genes. A phenotypic efflux inhibition assay was also employed, using the inhibitor Phe-Arg-â-naphtylamide (40 mg/L). DNA sequencing of oprD, pbp-2, pbp-3 and some of the efflux pump regulatory genes was conducted in selected isolates. Transferable carbapenem-resistance was studied in 11 isolates ...