Relationship between the distribution of cefepime minimum inhibitory concentrations and detection of extended-spectrum β-lactamase production among clinically important Enterobacteriaceae isolates obtained from patients in intensive care units in Taiwan: Results from the Surveillance of Multicenter Antimicrobial Resistance in Taiwan (SMART) in 2007

Background: The data on susceptibility of important cephalosporins against four Enterobacteriaceae members producing potential extended-spectrum β-lactamase (ESBL) collected from Taiwanese intensive care units are lacking. Methods: Minimum inhibitory concentrations (MICs) of cefotaxime, ceftazidime, and cefepime were determined using agar dilution method, against Escherichia coli (n=344), Klebsiella pneumoniae (n=359), Enterobacter cloacae (n=103), and Proteus mirabilis (n=78). Susceptibilities of these isolates to three cephalosporins were assessed according to MIC breakpoints recommended by the Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) in 2013. The double-disk synergy test using disks containing cefepime (30μg) with or without clavulanate (10μg) was applied to confirm production of ESBL for isolates with cephalosporin MIC≥2μg/mL. Results: A total of 175 isolates were verified as ESBL producers. The rates of cefepime susceptibility among the ESBL-producing isolates, according to CLSI (EUCAST) criteria, were 56.7% (22.4%) for E. coli, 61.3% (12.0%) for K. pneumoniae, 57.9% (31.6%) for E. cloacae, and 71.4% (7.1%) for P. mirabilis. Using different cefepime MIC breakpoints (MICs≥16μg/mL recommended by CLSI criteria and ≥2μg/mL by EUCAST criteria) to define nonsusceptibility, we found that both criteria were poorer at predicting ESBL producers among K. pneumoniae and E. cloacae than among the other two species. In addition, we also found that the cefepime MIC level of 1.0μg/mL best distinguished non-ESBL- from ESBL-producing K. pneumoniae and E. cloacae. Conclusion: To detect ESBLs, CLSI should revise the cefepime MIC breakpoint against Enterobacteriaceae.