Overexpression of AmpC and efflux pumps in XXXX isolates from bloodstream infections: prevalence and impact on resistance in a Spanish multicenter study.

@entity2892 @entity796 @entity2890 @entity6944 @entity2177 @entity7120 @entity3400 @entity5505 @entity15598
The prevalence and impact of the overexpression of AmpC and efflux pumps were evaluated with a collection of 190 @entity796 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 @entity2892 -resistant isolates studied (25 representative isolates) showed inactivating mutations in oprD. Most of the isolates nonsusceptible to @entity3400 - @entity7120 (96%) and @entity5505 (84%) overexpressed ampC, while mexB (25%) and mexY (29%) overexpressions gained relevance among @entity6944 -nonsusceptible isolates. Nevertheless, the prevalence of mexY overexpression was highest among @entity2890 -nonsusceptible isolates (37%), and that of mexB was highest among meropenem-nonsusceptible isolates (33%). Regarding @entity2177 -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 @entity2177 -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 @entity796 isolates from bloodstream infections, whereas metallo-b-lactamases, detected in 2 isolates (1%) producing @entity15598 , although with increasing prevalences, were still uncommon.
