Pseudomonas aeruginosa may accumulate drug resistance mechanisms without losing its ability to cause bloodstream infections

Abstract

In this study, we systematically investigated the resistance mechanisms to beta-lactams, aminoglycosides, and fluoroquinolones of 120 bacteremic strains of Pseudomonas aeruginosa. Pulsed-field gel electrophoresis genotyping showed that 97 of these strains were represented by a single isolate, 10 by 2 and 1 by 3 clonally related isolates, respectively. Seventy-five percent (90 out of 120) of the bacteremic P. aeruginosa strains displayed a significant resistance to one or more of the tested antimicrobials (up to 11 for 1 strain). These strains were found to harbor a great diversity of resistance mechanisms (up to 7 in 1 strain), leading to various levels of drug resistance. Interestingly, 11 and 36% of the isolates appeared to overproduce the MexAB-OprM and MexXY-OprM efflux systems, respectively. Altogether, our results show that P. aeruginosa may accumulate intrinsic (overproduction of cephalosporinase AmpC, increased drug efflux, fluoroquinolone target mutations, and deficient production of porin OprD) and exogenous (production of secondary beta-lactamases and aminoglycoside-modifying enzymes) resistance mechanisms without losing its ability to generate severe bloodstream infections. Consequently, clinicians should be aware that multidrug-resistant P. aeruginosa may remain fully pathogenic.

FIG. 1.

Multidrug resistance in the bacteremic P. aeruginosa isolates. White bars represent the percentage of isolates exhibiting intermediate susceptibility or resistance (CLSI breakpoints) to a given number of antibiotics. Black bars refer to a microbiological definition of resistance (MIC, at least fourfold that of the reference strain PAO1).

FIG. 2.

Accumulation of distinct resistance mechanisms to antibiotics in the 120 bacteremic P. aeruginosa isolates. The black bars represent the rates of isolates exhibiting only intrinsic resistance mechanism(s) (overexpression of the AmpC β-lactamase, decreased production of porin OprD, up-regulation of efflux systems MexAB-OprM and/or MexXY-OprM, nonenzymatic resistance to aminoglycosides independent of MexXY-OprM, and mutation[s] in the QRDRs). The hatched bars represent the rates of isolates showing both intrinsic and exogenous (production of transferable β-lactamases and aminoglycoside-modification enzymes) mechanisms of resistance.