In Vitro Antibacterial Activity of Imipenem/Relebactam against Clinical Isolates in Japan.

Dai Kurihara, Satoru Matsumoto, Naoko Kishi, Yoshikazu Ishii, Masahiko Mori

Microbiology spectrum 2022 Apr 27

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Relebactam is a novel β-lactamase inhibitor of Ambler class A and C β-lactamases that has been developed in combination with imipenem/cilastatin for the treatment of carbapenem-resistant bacterial infections. In this study, we evaluated the in vitro antibacterial activity of imipenem/relebactam (IMR) against imipenem-nonsusceptible Enterobacterales and Pseudomonas aeruginosa isolates from Japan. Two sets of antibacterial susceptibility tests were conducted according to the susceptibility testing standard of the Clinical and Laboratory Standards Institute. In the first set, antibacterial susceptibility as measured by the MIC50/90 (MIC range) of IMR was assessed for the following 61 imipenem-nonsusceptible strains: 2 Enterobacter cloacae complex (not determined [0.25 μg/mL]), 33 Klebsiella aerogenes (0.5/1 μg/mL [0.5 to 1 μg/mL]), 2 Serratia marcescens (not determined [1 to 2 μg/mL]), and 24 P. aeruginosa (2/128 μg/mL [0.25 to >128 μg/mL]). In the second set, antibacterial susceptibility was assessed for the following 8 imipenem-nonsusceptible strains: 4 Escherichia coli, 1 E. cloacae complex and 3 Klebsiella pneumoniae. The MIC ranges of IMR for these strains were 0.25 to 0.5 μg/mL, 0.5 μg/mL, and 0.5 to 16 μg/mL, respectively. The antibacterial activity of IMR was similar to or lower than that of amikacin and comparable to or greater than those of other reference drugs. In conclusion, IMR has shown antibacterial activity against clinical isolates from Japan and, therefore, is expected to become a new therapeutic option for carbapenem-resistant infections in Japan. IMPORTANCE Carbapenem-resistant Enterobacterales and carbapenem-resistant Pseudomonas aeruginosa strains pose a global threat. Antibacterial activity of imipenem/relebactam (IMR) against clinical isolates of these bacteria from several global regions has been shown; however, as yet there are no reports on Japanese isolates. In this study, we evaluated the in vitro antibacterial activity of IMR against imipenem-nonsusceptible Enterobacterales and Pseudomonas aeruginosa isolates from Japan. The antibacterial activity of IMR against imipenem-nonsusceptible Enterobacterales was generally comparable to that of amikacin (AMK) and comparable to or higher than those of other reference drugs tested. The antibacterial activity of IMR against imipenem-nonsusceptible P. aeruginosa isolates was lower than that of AMK but comparable to or higher than those of other drugs. These results support the use of IMR as a new treatment option for infections due to Enterobacterales and P. aeruginosa strains that are resistant to existing β-lactams and other antibacterial agents.

Citation

Dai Kurihara, Satoru Matsumoto, Naoko Kishi, Yoshikazu Ishii, Masahiko Mori. In Vitro Antibacterial Activity of Imipenem/Relebactam against Clinical Isolates in Japan. Microbiology spectrum. 2022 Apr 27;10(2):e0223521