Activities of imipenem-relebactam combination against carbapenem-nonsusceptible Enterobacteriaceae in Taiwan

Tsung-Ying Yang; Ya-Ju Hsieh; Li-Ting Kao; Guan Hong Liu; Shao-Hsuan Lian; Liang-Chun Wang; I-Ling Lin; Hsian-Yu Wang; Sung-Pin Tseng; Po-Liang Lu

Journal of Microbiology, Immunology and Infection (Feb 2022)

Activities of imipenem-relebactam combination against carbapenem-nonsusceptible Enterobacteriaceae in Taiwan

Tsung-Ying Yang,
Ya-Ju Hsieh,
Li-Ting Kao,
Guan Hong Liu,
Shao-Hsuan Lian,
Liang-Chun Wang,
I-Ling Lin,
Hsian-Yu Wang,
Sung-Pin Tseng,
Po-Liang Lu

Affiliations

Tsung-Ying Yang: Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Taiwan
Ya-Ju Hsieh: Department of Medical Imaging and Radiological Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan
Li-Ting Kao: Orthopaedic Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Guan Hong Liu: Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Taiwan
Shao-Hsuan Lian: Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Taiwan
Liang-Chun Wang: Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung, Taiwan
I-Ling Lin: Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Taiwan; Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
Hsian-Yu Wang: Graduate Institute of Animal Vaccine Technology, College of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung, Taiwan
Sung-Pin Tseng: Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Taiwan; Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung, Taiwan; Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan; Corresponding author. Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, 100, Shih-Chuan 1stRoad, TaiwanRoad, Kaohsiung, Taiwan. Fax: (886)-7-3113449.
Po-Liang Lu: Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Post-Baccalaureate Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Corresponding author. Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.

Journal volume & issue: Vol. 55, no. 1
pp. 86 – 94

Abstract

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Background: Imipenem-relebactam is a new β-lactam and β-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 carbapenem-nonsusceptible 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 carbapenem-nonsusceptible 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 metallo-carbapenemase 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.

Published in Journal of Microbiology, Immunology and Infection

ISSN: 1684-1182 (Print)
Publisher: Elsevier
Country of publisher: Hong Kong
LCC subjects: Science: Microbiology
Website: https://www.sciencedirect.com/journal/journal-of-microbiology-immunology-and-infection

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