Accuracy of Carbapenem Nonsusceptibility for Identification of KPC-Possessing Enterobacteriaceae by Use of the Revised CLSI Breakpoints

Abstract

Using the updated 2010 CLSI carbapenem breakpoints for the Enterobacteriaceae, nonsusceptibility to ertapenem and imipenem predicted the presence of bla KPC poorly, especially among Escherichia coli and Enterobacter species. In regions where KPC-producing bacteria are endemic, testing for nonsusceptibility to meropenem may provide improved accuracy in identifying these isolates.The worldwide spread of the carbapenemase KPC has been unrelenting, in part because of difficulty in its detection. Using breakpoints defined prior to 2010, it was well documented that many KPC-possessing isolates had imipenem and meropenem MICs reported in the susceptible range (1, 2, 19). Approximately 75% of isolates of Escherichia coli (13), 60% of isolates of Klebsiella pneumoniae (8), and 25% of Enterobacter species isolates (14) that possess KPC were found to be susceptible to imipenem and/or meropenem. In particular, isolates of K. pneumoniae with underexpression of bla KPC or with the presence of functional OmpK36 have lower carbapenem MICs (3,10,12). Most isolates, including 50% of E. coli (13), 95% Ϫ100% of K. pneumoniae (8,16), and 100% of Enterobacter species isolates, have been found to be resistant to ertapenem. Therefore, ertapenem has been suggested as the agent of choice for screening of Enterobacteriaceae for KPC ␤-lactamases (1, 2, 16).However, ertapenem resistance has been found in K. pneumoniae and Enterobacter species lacking a carbapenem-hydrolyzing ␤-lactamase (7,16,20). The combination of a class C cephalosporinase and porin deficiency contributes to ertapenem resistance; many of these isolates remain susceptible to the other carbapenems (9). Therefore, using ertapenem alone as the class agent for carbapenem susceptibility testing, particularly in regions where carbapenemases are infrequent (15), may inappropriately eliminate carbapenems as therapeutic agents against these isolates.In 2010, the CLSI issued new breakpoints for carbapenems and several cephalosporins (5). The performance of these guidelines and the optimal strategy for detecting KPC-possessing isolates in regions of endemicity have not been determined. In this report, we evaluate the updated guidelines for detecting KPC-possessing members of the Enterobacteriaceae and provide recommendations for clinical laboratories when these guidelines are implemented.Single patient isolates of E. coli, K. pneumoniae, and Enterobacter species were collected during borough-wide surveillance studies performed in 2006 and 2009, as previously described (11, 13). The overall susceptibilities for some of the isolates have been previously reported (11, 13). Susceptibilities to piperacillin-tazobactam, ceftazidime, ertapenem, imipenem, and meropenem were tested by the agar dilution method according to CLSI standards (4). All cephalosporin-resistant isolates were screened for the presence of bla KPC , using previously reported primers and PCR conditions (2). Select isolates resistant to ertapenem but lacking bla KPC were screened for the presence of bla CMY and bla CTX-M ...

High prevalence of Klebsiella pneumoniae carbapenemase-mediated resistance in K. pneumoniae isolates from Egypt

“…To our knowledge, this is the first published report of KPC-producing K. pneumoniae isolated from patients at a tertiary care hospital in Egypt. In our study we used ertapenem to screen for carbapenemases, as ertapenem is the least active carbapenem against KPCs [26] and as the use of this drug in automated or manual susceptibility testing has been found to be a highly sensitive method for the detection of KPCs [26,27]. Despite the limited number of isolates included, we were able to show a high prevalence of ertapenem non-susceptibility, accounting for 44.4% of K. pneumoniae isolates tested.…”

Use of Faropenem as an Indicator of Carbapenemase Activity in the Enterobacteriaceae

“…A number of studies have examined disc susceptibility testing with carbapenems as a means of predicting carbapenemase activity, with particular focus on KPC carbapenemase (12)(13)(14)(15). Based on the available evidence, zone diameter cutoff values for detecting putative carbapenemase producers were proposed by a EUCAST subcommittee for detection of resistance mechanisms in December 2012 (16).…”

Temocillin and meropenem to discriminate resistance mechanisms leading to decreased carbapenem susceptibility with focus on OXA-48 in Enterobacteriaceae

“…A wide variety of enzymes other than carbapenemases, as well as porin changes or a combination of both, can result in phenotypes not distinguishable by a single phenotypic test and new enzymes are being steadily described . The question of whether one should screen for carbapenemase production and, if yes, which ß‐lactam antibiotic should be used as a substrate (and breakpoint), is difficult to answer .…”