Abstract
BackgroundCarbapenemase-producing Enterobacteriaceae (CPE) are difficult to identify among carbapenem non-susceptible Enterobacteriaceae (NSE). We designed phenotypic strategies giving priority to high sensitivity for screening putative CPE before further testing.MethodsPresence of carbapenemase-encoding genes in ertapenem NSE (MIC > 0.5 mg/l) consecutively isolated in 80 French laboratories between November 2011 and April 2012 was determined by the Check-MDR-CT103 array method. Using the Mueller-Hinton (MH) disk diffusion method, clinical diameter breakpoints of carbapenems other than ertapenem, piperazicillin+tazobactam, ticarcillin+clavulanate and cefepime as well as diameter cut-offs for these antibiotics and temocillin were evaluated alone or combined to determine their performances (sensitivity, specificity, positive and negative likelihood ratios) for identifying putative CPE among these ertapenem-NSE isolates. To increase the screening specificity, these antibiotics were also tested on cloxacillin-containing MH when carbapenem NSE isolates belonged to species producing chromosomal cephalosporinase (AmpC) but Escherichia coli.ResultsOut of the 349 ertapenem NSE, 52 (14.9%) were CPE, including 39 producing OXA-48 group carbapenemase, eight KPC and five MBL. A screening strategy based on the following diameter cut offs, ticarcillin+clavulanate <15 mm, temocillin <15 mm, meropenem or imipenem <22 mm, and cefepime <26 mm, showed 100% sensitivity and 68.1% specificity with the better likelihood ratios combination. The specificity increased when a diameter cut-off <32 mm for imipenem (76.1%) or meropenem (78.8%) further tested on cloxacillin-containing MH was added to the previous strategy for AmpC-producing isolates.ConclusionThe proposed strategies that allowed for increasing the likelihood of CPE among ertapenem-NSE isolates should be considered as a surrogate for carbapenemase production before further CPE confirmatory testing.
Highlights
Carbapenemase-producing Enterobacteriaceae (CPE) are difficult to identify among carbapenem nonsusceptible Enterobacteriaceae (NSE)
Looking for CPE among all carbapenem NS isolates is difficult, and the routine clinical laboratory is in need of simple tools allowing for the rapid suspicion of CPE among carbapenem NSE isolates before further testing by more specific tests
As we reported a low proportion of CPE among non-selected carbapenem NSE in France in 2011–2012 [5], the French committee on antibiotic susceptibility testing (CA-SFM) affiliated to the European committee on antimicrobial susceptibility testing (EUCAST) raised interest in using this unbiased isolates collection to develop a screening strategy that could be applied in all laboratories to eliminate with certainty carbapenemase-negative isolates among carbapenem NSE
Summary
Carbapenemase-producing Enterobacteriaceae (CPE) are difficult to identify among carbapenem nonsusceptible Enterobacteriaceae (NSE). Preventing the spread of carbapenemase-producing Enterobacteriaceae (CPE) is a priority because it may lead to therapeutic dead end [1]. Rapid detection of CPE in the laboratory is of paramount importance [2]. This detection is complex because carbapenemases display various hydrolytic activities with regard to β-lactams and mechanisms other than carbapenemase production, namely overproduction of AmpC β-lactamase and/or production of ESBL in isolates displaying reduced outer membrane permeability, are involved in resistance to carbapenems. Appropriate studies have shown that the incidence of CPE is very low in some countries and that the other resistance mechanisms are the most frequent in carbapenem non-susceptible Enterobacteriaceae (NSE) [3,4,5]. Looking for CPE among all carbapenem NS isolates is difficult, and the routine clinical laboratory is in need of simple tools allowing for the rapid suspicion of CPE among carbapenem NSE isolates before further testing by more specific tests
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