Imipenem and meropenem Vitek 2 MICs were evaluated for a panel of 104 Enterobacteriaceae for identification of carbapenemase producers. The sensitivity and specificity values for the new CLSI interpretative criteria (CLSI document M100-S20-U, 2010) were 98% and 83% for imipenem and 76% and 83% for meropenem, respectively. We propose an algorithm that is highly sensitive (98%) and specific (94%) for carbapenemase screening based on the combined use of imipenem and meropenem MICs.Carbapenems are increasingly utilized as drugs of last resort against a variety of infections due to the emergence of extended-spectrum--lactamase (ESBL)-producing Enterobacteriaceae (23). The emergence of carbapenem-resistant Enterobacteriaceae is therefore worrisome, as the antimicrobial armamentarium is consequently restricted (6, 17). The resistance of Enterobacteriaceae to carbapenems could be related to carbapenemases or to a dual mechanism associating an outer membrane permeability defect with -lactamases such as AmpC cephalosporinase and ESBLs, particularly with the presence of CTX-M variants (9-11, 15, 16, 27, 29). The vast majority of acquired carbapenemases belong to three of the four known classes of -lactamases, namely, Ambler class A (KPC, Sme, NMC-A, IMI, and some allelic variants of the GES/IBC enzymes), Ambler class B (metallo--lactamases [MBLs]), and Ambler class D (oxacillinases [OXAs]) (5). The locations of carbapenemase genes on highly mobile genetic elements have contributed to their rapid spread and the frequent cotransfer of multiple other antibiotic resistance factors (6,18,19). The ability to limit the spread of carbapenemase producers will require effective laboratory screening methods to rapidly identify patients infected with these organisms. Automated antimicrobial susceptibility testing systems, such as Vitek 2 (bioMérieux, Marcy L'Etoile, France), are commonly used in microbiology laboratories to decrease the laboratory turnaround time. However, several reports have questioned the ability of Vitek 2 to identify carbapenemase producers (1,2,17,25,28). Previous reports suggest an ertapenem MIC of Ն4.0 g/ml (formerly, an ertapenem resistance result [7]) as the most accurate way to detect KPC carbapenemase (2, 17). In Argentina, among several other countries in which CTX-M is endemic, a large proportion of nosocomial Enterobacteriaceae display ertapenem resistance (about 5%, 15%, 20%, and 25% of the Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii, and Enterobacter species strains, respectively, from WHONET-Argentina Network [n ϭ 55,351]), although most of them did not produce carbapenemases, as determined by molecular methods. The selection of CTX-M-2-producing mutants with porin loss was responsible for this ertapenem resistance. With ertapenem and meropenem as indicators (MICs of Ն4 g/ml and Ն8 g/ml, respectively), Vitek 2 was not able to differentiate true resistance mediated by carbapenemases from that mediated by AmpC cephalosporinases and ESBLs in combination with an outer membrane perme...