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Antimicrobial Agents and Chemotherapy, November 2007, p. 4062-4070, Vol. 51, No. 11
0066-4804/07/$08.00+0     doi:10.1128/AAC.00148-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Resistance Mechanisms of Multiresistant Pseudomonas aeruginosa Strains from Germany and Correlation with Hypermutation ^,

University of Bonn, Institute for Medical Microbiology, Immunology and Parasitology, Pharmaceutical Microbiology Unit, Meckenheimer Allee 168, 53115 Bonn, Germany,¹ University of Jena, Institute for Medical Microbiology, Germany²

Received 1 February 2007/ Returned for modification 8 April 2007/ Accepted 1 September 2007

In this study, we analyzed the mechanisms of multiresistance for 22 clinical multiresistant and clonally different Pseudomonas aeruginosa strains from Germany. Twelve and 10 strains originated from cystic fibrosis (CF) and non-CF patients, respectively. Overproduction of the efflux systems MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY-OprM was studied. Furthermore, loss of OprD, alterations in type II topoisomerases, AmpC overproduction, and the presence of 25 acquired resistance determinants were investigated. The presence of a hypermutation phenotype was also taken into account. Besides modifications in GyrA (91%), the most frequent mechanisms of resistance were MexXY-OprM overproduction (82%), OprD loss (82%), and AmpC overproduction (73%). Clear differences between strains from CF and non-CF patients were found: numerous genes coding for aminoglycoside-modifying enzymes and located, partially in combination with ß-lactamase genes, in class 1 integrons were found only in strains from non-CF patients. Furthermore, multiple modifications in type II topoisomerases conferring high quinolone resistance levels and overexpression of MexAB-OprM were exclusively detected in multiresistant strains from non-CF patients. Correlations of the detected phenotypes and resistance mechanisms revealed a great impact of efflux pump overproduction on multiresistance in P. aeruginosa. Confirming previous studies, we found that additional, unknown chromosomally mediated resistance mechanisms remain to be determined. In our study, 11 out of 12 strains and 3 out of 10 strains from CF patients and non-CF patients, respectively, were hypermutable. This extremely high proportion of mutator strains should be taken into consideration for the treatment of multiresistant P. aeruginosa.

Published ahead of print on 17 September 2007.

Supplemental material for this article may be found at http://aac.asm.org/.

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