Defining Extended Spectrum b-Lactamases: Implications of Minimum Inhibitory Concentration- Based Screening Versus Clavulanate Confirmation Testing

Introduction: While the Clinical and Laboratory Standards Institute (CLSI) recommends against routine screening for extended spectrum b-lactamases (ESBLs), knowledge of these data can provide valuable insights regarding epidemiology and drug therapy decisions. The purpose of this study was to compare the impact of minimum inhibitory concentration (MIC)-based screening versus phenotypic confirmatory testing of ESBLs on the susceptibility profile of selected antimicrobials. Methods: Broth microdilution MICs were determined for various antimicrobial agents against a collection contemporary clinical Escherichia coli and Klebsiella pneumoniae isolates. Isolates identified as ESBL-positive by MIC screening were then subjected to confirmatory phenotypic testing. Percent susceptibility was based on CLSI or United States Food and Drug Administration breakpoints. Results: Four-hundred and forty-two (18%) isolates screened positive for ESBL production. Of these, 274 (62%) were confirmed positive for ESBL production; 28 (10%) were also carbapenem non-susceptible. We found an under-prediction of activity for ceftolozane/tazobactam (C/T), ertapenem (ETP), meropenem (MEM), and piperacillin/tazobactam (TZP) when considering only the screen-positive testing. Conclusion: For agents with potential activity against ESBLs such as C/T, TZP, ETP, and MEM, reduced susceptibility was noted when only considering the MIC screen-positive test. Although phenotypic screening selects for resistant organisms, inclusion of other genotypes besides ESBL (i.e., AmpC, carbapenemase) may falsely under-predict the potency against some ESBL producers and may limit applicability of surveillance data to geographic areas not plagued with carbapenemase producers. Funding: Cubist Pharmaceuticals. Electronic supplementary material The online version of this article (doi:10.1007/s40121-015-0094-6) contains supplementary material, which is available to authorized users. C. A. Sutherland J. L. Crandon D. P. Nicolau (&) Center for Anti Infective Research and Development, Hartford Hospital, Hartford, CT, USA e-mail: [email protected] Present Address: J. L. Crandon Actavis plc, Jersey City, NJ, USA Infect Dis Ther (2015) 4:513–518 DOI 10.1007/s40121-015-0094-6