Enhanced efficacy of imipenem-colistin combination therapy against multiple-drug-resistant Enterobacter cloacae: in vitro activity and a Galleria mellonella model

Journal of Microbiology, Immunology, and Infection = Wei Mian Yu Gan Ran Za Zhi
Haifei YangJiabin Li

Abstract

To investigate the in vitro and in vivo activity of imipenem-colistin combination against multidrug-resistant Enterobacter cloacae infections in order to determine whether it should be explored further. The antimicrobial activity of colistin alone and in combination with imipenem was assessed versus an imipenem-susceptible isolate, E. cloacae GN1059, or an imipenem-resistant strain, E. cloacae GN0791, isolated in Anhui, China. The potential synergy of imipenem-colistin was evaluated using a checkerboard assay, as well as static time-kill experiments at 1× and 2× minimum inhibitory concentration (MIC). A simple invertebrate model (Galleria mellonella) was developed to assess the in vivo efficacy of imipenem-colistin in treating E. cloacae infection. In checkerboard assays, synergy (defined as a fractional inhibitory concentration index of ≤ 0.5) was observed between imipenem and colistin for both isolates tested. In time-kill assays, the combination of imipenem-colistin at 1× or 2× MIC resulted in complete killing of both strains. In the G. mellonella larvae model infected with lethal doses of E. cloacae, the combination therapy led to significantly increased survival of the larvae as compared with imipenem or colistin monothera...Continue Reading

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Citations

Apr 4, 2017·Expert Opinion on Biological Therapy·Josep M SierraMiguel Viñas
Feb 15, 2019·Frontiers in Microbiology·Chau-Chyun SheuPo-Ren Hsueh
Apr 17, 2019·Frontiers in Microbiology·Mansura S MulaniKarishma R Pardesi
Apr 13, 2017·Frontiers in Cellular and Infection Microbiology·James P DaltonSiouxsie Wiles
Sep 23, 2020·Pathogens and Disease·Monalessa Fábia PereiraDenise Mara Soares Bazzolli
Feb 6, 2021·Pathogens·Gustavo Henrique Rodrigues Vale de MacedoLuís Cláudio Nascimento da Silva
Feb 24, 2021·Antimicrobial Agents and Chemotherapy·Charles OmolloDigby F Warner

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