title: Overexpression of AmpC and efflux pumps in Pseudomonas aeruginosa isolates from bloodstream infections: prevalence and impact on resistance in a Spanish multicenter study.
abstract: The prevalence and impact of the overexpression of AmpC and efflux pumps were evaluated with a collection of 190 Pseudomonas aeruginosa isolates recovered from bloodstream infections in a 2008 multicenter study (10 hospitals) in Spain. The MICs of a panel of 13 antipseudomonal agents were determined by microdilution, and the expressions of ampC, mexB, mexY, mexD, and mexF were determined by real-time reverse transcription (RT)-PCR. Up to 39% of the isolates overexpressed at least one of the mechanisms. ampC overexpression (24.2%) was the most prevalent mechanism, followed by mexY (13.2%), mexB (12.6%), mexF (4.2%), and mexD (2.2%). The overexpression of mexB plus mexY, documented for 5.3% of the isolates, was the only combination showing a significantly (P=0.02) higher prevalence than expected from the frequencies of the individual mechanisms (1.6%). Additionally, all imipenem-resistant isolates studied (25 representative isolates) showed inactivating mutations in oprD. Most of the isolates nonsusceptible to piperacillin-tazobactam (96%) and ceftazidime (84%) overexpressed ampC, while mexB (25%) and mexY (29%) overexpressions gained relevance among cefepime-nonsusceptible isolates. Nevertheless, the prevalence of mexY overexpression was highest among tobramycin-nonsusceptible isolates (37%), and that of mexB was highest among meropenem-nonsusceptible isolates (33%). Regarding ciprofloxacin-resistant isolates, besides the expected increased prevalence of efflux pump overexpression, a highly significant link to ampC overexpression was documented for the first time: up to 52% of ciprofloxacin-nonsusceptible isolates overexpressed ampC, sharply contrasting with the 24% documented for the complete collection (P<0.001). In summary, mutation-driven resistance was frequent in P. aeruginosa isolates from bloodstream infections, whereas metallo-β-lactamases, detected in 2 isolates (1%) producing VIM-2, although with increasing prevalences, were still uncommon.
authors.affiliation: Servicio de Microbiología, Hospital Universitario Son Espases, Ctra. Valldemossa 79, 07010 Palma de Mallorca, Spain.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Cabot
authors.forename: Alain A
authors.initials: AA
authors.lastname: Ocampo-Sosa
authors.forename: Fe
authors.initials: F
authors.lastname: Tubau
authors.forename: María D
authors.initials: MD
authors.lastname: Macia
authors.forename: Cristina
authors.initials: C
authors.lastname: Rodríguez
authors.forename: Bartolomé
authors.initials: B
authors.lastname: Moya
authors.forename: Laura
authors.initials: L
authors.lastname: Zamorano
authors.forename: Cristina
authors.initials: C
authors.lastname: Suárez
authors.forename: Carmen
authors.initials: C
authors.lastname: Peña
authors.forename: Luis
authors.initials: L
authors.lastname: Martínez-Martínez
authors.forename: Antonio
authors.initials: A
authors.lastname: Oliver
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics*; D015780:Carbapenems / Q000494:pharmacology; D000077723:Cefepime; D002442:Ceftazidime / Q000494:pharmacology; D002511:Cephalosporins / Q000494:pharmacology; D015378:Imipenem / Q000494:pharmacology; D026901:Membrane Transport Proteins / Q000235:genetics; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D018272:Porins / Q000235:genetics; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics* / Q000472:pathogenicity; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013845:Thienamycins / Q000494:pharmacology; D001618:beta-Lactamases / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D015780:Carbapenems; D002511:Cephalosporins; D026901:Membrane Transport Proteins; C118597:MexB protein, Pseudomonas aeruginosa; C402792:MexZ protein, Pseudomonas aeruginosa; D018272:Porins; D013845:Thienamycins; C077157:OprD protein, Pseudomonas aeruginosa; D015378:Imipenem; D000077723:Cefepime; D002442:Ceftazidime; C048795:AmpC beta-lactamases; D001618:beta-Lactamases; D000077731:Meropenem