Comparison of 3 Etest® methods and time-kill assay for determination of antimicrobial synergy against carbapenemase-producing Klebsiella species

Increasing global antibiotic resistance has resulted in more use of antibiotic combinations. There is a lack of a gold standard for in vitro testing of these combinations for synergy or antagonism. Time-kill assay (TKA) may be used but is labor intensive and not practical for clinical use. Etest (R) synergy methods are more rapid and easier to perform, but there is no agreement regarding which method is best. We tested 31 clinical genetically unique Klebsiella pneumoniae carbapenemase-producing Klebsiella isolates with the combination of meropenem and polymyxin B by TKA and 3 Etest methods, each in triplicate: Method 1, MIC:MIC; Method 2, direct overlay; and Method 3, cross. Overall, testing with Etest synergy methods showed the following agreement with TKA: Method 1: 25/31 (80.6%), Method 2: 7/31 (22.6%), and Method 3: 8/31 (25.8%). The MIC:MIC method had the highest agreement (80.6%, kappa = 0.59, P < 0.001) and should be evaluated more extensively. (C) 2013 Elsevier Inc. All rights reserved.