Activities of imipenem-relebactam combination against carbapenemnonsusceptible Enterobacteriaceae in Taiwan

Abstract

Abstract Background: Imipenem-relebactam is a new b-lactam and b-lactamase inhibitor combination to treat carbapenem-resistant gram-negative bacteria infections. However,difference in carbapenem resistant mechanisms existed with geographic variations. Objective: To evaluate the susceptibility of imipenem-relebactam to 660 carbapenemnonsusceptible Enterobacteriaceae isolates in Taiwan and to identify the in vivo efficacy with a Caenorhabditis elegans model. Methods: 188 carbapenem-nonsusceptible Escherichia coli isolates and 472 carbapenemnonsusceptible Klebsiella pneumoniae isolates were collected from a national surveillance study in Taiwan. The antimicrobial susceptibility profiles and carbapenemase distributions were determined. An agar dilution method was performed to evaluate the in vitro activities of imipenem monotherapy and imipenem-relebactam combination. Contributions of metallocarbapenemase to imipenem-relebactam susceptibility was investigated via EDTA treatment. A C. elegans model was used to evaluate the in vivo efficacy of imipenem-relebactam combination. Results: 87.8% and 82.2% susceptibility to imipenem-relebactam was observed for 188 carbapenem-nonsusceptible E. coli and 472 carbapenem-nonsusceptible K. pneumoniae, respectively. However, poor activities of imipenem-relebactam was observed against 23 metallo-carbapenemase producers tested in this study. In the in vivo C. elegans model, imipenem-relebactam significantly rescued nematodes from the infection of a blaKPC-producing K. pneumoniae isolate. Conclusion: Our study supports that imipenem-relebactam is a potential therapy against carbapenem-nonsusceptible Enterobacteriaceae, and to our knowledge, this is the first report of evaluation for imipenem-relebactam efficacy against carbapenem-nonsusceptible Enterobacteriaceae in Taiwan.