Performance of the EUCAST disc diffusion method and two MIC methods in detection of Enterobacteriaceae with reduced susceptibility to meropenem: The NordicAST CPE study

Abstract

Objectives: To examine performance of EUCAST disc diffusion and supplementary MIC methods for detection of Enterobacteriaceae with reduced susceptibility to meropenem using EUCAST screening recommendations. Methods: Sixty-one Nordic laboratories delivered data on EUCAST disc diffusion (n " 61), semi-automated meropenem MIC (n " 23; VITEK2, n " 20 and Phoenix, n " 3) and gradient meropenem MIC (n " 58) methods. The strains (n " 27) included the major carbapenemase classes (A, n " 4; B, n " 9; D, n " 6) involved in the global spread of carbapenemase-producing Enterobacteriaceae (CPE) and non-CPE strains (n " 8) covering a range of broth microdilution (BMD) meropenem MICs. Results: A triplicate Klebsiella variicola (meropenem MIC 0.5 mg/L) harbouring OXA-48 and Escherichia coli ATCC 25922 showed an overall good precision. Meropenem zone diameters below the EUCAST screening cut-off (,27 mm) were reported for strains with MIC 1 mg/L (n " 21), irrespective of resistance mechanism. For three strains (MIC " 0.5 mg/L) with OXA-48/-181, eight laboratories provided meropenem zone diameters above the screening cut-off. Very major errors (VMEs) were not observed. The overall distributions of major errors (MEs) and minor errors (mEs) were 9% and 36% (disc diffusion), 26% and 18% (VITEK2) and 7% and 20% (gradient MIC), respectively. Differences in ME and mE distributions between disc diffusion and MIC gradient tests compared with semi-automated methods were significant (P, 0.0001), using BMD MICs as a reference for categorization. Conclusions: The EUCAST disc diffusion method is a robust method to screen for CPE but isolates with meropenem MICs,1 mg/L pose challenges. The high ME rate in semi-automated methods might deter appropriate use of carbapenems in CPE infections with limited therapeutic options.