Accumulation of carbapenem resistance mechanisms in VIM-2-producing Pseudomonas aeruginosa under selective pressure

Abstract

Pseudomonas aeruginosa has the potential to achieve resistance to carbapenems via the acquisition of carbapenemase-encoding genes, the downregulation of the OprD porin, the overexpression of efflux systems and the overproduction of cephalosporinases. One hundred and fifty carbapenem-non-susceptible isolates from 2008 to 2010 were screened for carbapenemase production, OprD porin loss, efflux pumps overexpression and inducible AmpC beta-lactamase production. For comparison reasons, the presence of the same mechanisms was also assessed in a previous collection of 30 carbapenem-non-susceptible P. aeruginosa isolated between 2003 and 2005. Results showed the accumulation of various resistance mechanisms among VIM-2 producers isolated between 2008 and 2010 with a parallel considerable increase in imipenem MIC90 and the geometric mean of the MIC values of imipenem and meropenem between the two study groups. The accumulation of carbapenem resistance mechanisms highlights the potential of this formidable pathogen for evolutionary success under antibiotic selective pressure.

Virulence Genes in Pseudomonas Aeruginosa Strains Isolated at Suez Canal University Hospitals with Respect to the Site of Infection and Antimicrobial Resistance

“…The variations in the results of the antibiotic resistance might be referred to the difference in the pattern of drug use in different parts of the world and due to the several mechanisms that have been reported for P. aeruginosa, including: 1) Reduced expression or loss of OprD porin causing reduced antibiotic permeability, 2) Overexpression of MexAB-OprM pump which increases antibiotic ef lux, 3) Production of β-lactams and aminoglycosides inactivating enzymes, 4) Mutations of gyrases and topoisomerases which cause luoroquinolone resistance. These mechanisms in combination lead to multiple drug resistance [38,39].…”

Carbapenem resistance: overview of the problem and future perspectives

“…Moreover, it has been shown that carbapenemresistant Gram-negative nosocomial pathogens will continue to evolve accumulating more carbapenem-resistance mechanisms [Meletis et al 2014b], or more than one carbapenemase-encoding gene [Meletis et al 2015a]. This will lead in many cases to increased carbapenem MICs ruling out the best-to-date therapeutic choice against carbapenemase producers, which is the combined treatment including at least one carbapenem.…”

Role of the Outer Membrane Protein OprD2 in Carbapenem-Resistance Mechanisms of Pseudomonas aeruginosa

“…However, the accumulation of carbapenem-resistant mechanisms could probably further increase carbapenem MICs, leaving even fewer therapy options for clinicians against the multi-drug resistant P . aeruginosa [ 3 ]. Studies on the antimicrobial resistance in P .…”