Emergence of extensive-drug-resistant Pseudomonas aeruginosa in a French university hospital

Abstract

The aim of this study was to describe the molecular epidemiology and the mechanisms of resistance to beta-lactams of emerging extensive-drug-resistant Pseudomonas aeruginosa (XDRPA) in a tertiary-care university hospital over a three-year period. Analysis included antimicrobial susceptibility profiling and pulsed-field gel electrophoresis (PFGE). Resistance mechanisms to beta-lactams were identified: production of naturally occurring and acquired beta-lactamases, overproduction of MexAB-OprM and MexXY efflux systems and loss of porin OprD were assessed. Eighteen patients were colonised or infected with XDRPA which remained susceptible to colistin and, to a lesser extent, to rifampicin. beta-lactam resistance was, in most cases, due to the overproduction of AmpC, overproduction of the MexXY efflux system and loss of porin OprD. One isolate produced the class D extended-spectrum oxacillinase (OXA-ESBL) Oxa-28, but none produced metallo-beta-lactamase (MBL) or class A extended-spectrum beta-lactamase (ESBL). The XDRPA clustered in eight PFGE patterns and both the acquisition and loss of resistance determinants was observed within a single clone during its spread. The emergence of XDRPA isolates in our university hospital has been characterised by genotypic heterogeneity, variation of mechanisms of resistance to beta-lactams in a single clone and the predominance of chromosomally encoded resistance mechanisms.

Emergence of Imipenem-Resistant Gram-Negative Bacilli in Intestinal Flora of Intensive Care Patients

“…Overproduction of intrinsic ␤-lactamase AmpC was assessed phenotypically by restoration of susceptibility to ceftazidime on Mueller-Hinton agar plates containing 1,000 mg/liter cloxacillin. Porin OprD-deficient mutants and overproduction of MexAB efflux system were detected as described previously (26).…”

The prophylactic effects of human IgG derived from sera containing high anti-PcrV titers against pneumonia-causingPseudomonas aeruginosa

“…[3][4][5] P. aeruginosa clinical isolates are often resistant to most b-lactams and fluoroquinolones and, sometimes, resistant to aminoglycosides, such as gentamicin and amikacin, thus categorizing them as multi-drug resistant P. aeruginosa (MDRP). 4,[6][7][8][9] Limitations in the number of effective antimicrobial agents for treating MDRP infections leads to the high mortality rates associated with the acute lung injury induced by this bacterium. 5 While seeking new prophylactic or therapeutic strategies that do not rely on conventional antimicrobial agents, we have investigated the use of an immunotherapy approach that targets the P. aeruginosa type III secretion system.…”

Oxidative Stress Induction of the MexXY Multidrug Efflux Genes and Promotion of Aminoglycoside Resistance Development in Pseudomonas aeruginosa

“…Upregulation of mexXY by antimicrobials or fmt/ folD mutations is dependent upon a gene, PA5471, encoding a conserved hypothetical protein whose expression is also promoted by ribosome-disrupting antimicrobials (34) and by fmt/ folD mutations (6). Despite this primary link to translation disruption, the MexXY-OprM efflux system is a significant determinant of resistance to antimicrobials in clinical isolates, particularly aminoglycosides (19,40,52) but also ␤-lactams (3,19,23,37,51). Indeed, while it is uncommon as a mechanism of aminoglycoside resistance in most clinical strains of P. aeruginosa, MexXY-OprM is the predominant mechanism of resistance to these agents in cystic fibrosis (CF) isolates (19,40,52).…”