Haifei Yang1, Guosheng Chen1, Lifen Hu1, Yanyan Liu2, Jun Cheng1, Ying Ye3, Jiabin Li4. 1. Department of Infectious Disease, The First Affiliated Hospital of Anhui Medical University, Hefei, China. 2. Department of Molecular Biology, Institute of Bacterium Resistance, Anhui Medical University, Hefei, China; Department of Molecular Biology, Anhui Center for Surveillance of Bacterial Resistance, Hefei, China. 3. Department of Infectious Disease, The First Affiliated Hospital of Anhui Medical University, Hefei, China; Department of Molecular Biology, Institute of Bacterium Resistance, Anhui Medical University, Hefei, China; Department of Molecular Biology, Anhui Center for Surveillance of Bacterial Resistance, Hefei, China. 4. Department of Infectious Disease, The First Affiliated Hospital of Anhui Medical University, Hefei, China; Department of Molecular Biology, Institute of Bacterium Resistance, Anhui Medical University, Hefei, China; Department of Molecular Biology, Anhui Center for Surveillance of Bacterial Resistance, Hefei, China; Department of Infectious Diseases, Chaohu Hospital of Anhui Medical University, Hefei, China. Electronic address: lijiabin948@vip.sohu.com.
Abstract
BACKGROUND/ PURPOSE: 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. METHODS: 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. RESULTS: 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 monotherapy alone (p < 0.05). CONCLUSION: This is the first report demonstrating the efficacy of antimicrobial agents in the G. mellonella larvae model of infections caused by E. cloacae. Our study suggested that imipenem-colistin combination was highly active against E. cloacae both in vitro and in the simple invertebrate model, and provided preliminary in vivo evidence that such combination might be useful therapeutically.
BACKGROUND/ PURPOSE: To investigate the in vitro and in vivo activity of imipenem-colistin combination against multidrug-resistant Enterobacter cloacaeinfections in order to determine whether it should be explored further. METHODS: 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. cloacaeinfection. RESULTS: 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 monotherapy alone (p < 0.05). CONCLUSION: This is the first report demonstrating the efficacy of antimicrobial agents in the G. mellonella larvae model of infections caused by E. cloacae. Our study suggested that imipenem-colistin combination was highly active against E. cloacae both in vitro and in the simple invertebrate model, and provided preliminary in vivo evidence that such combination might be useful therapeutically.
Authors: Gustavo Henrique Rodrigues Vale de Macedo; Gabrielle Damasceno Evangelista Costa; Elane Rodrigues Oliveira; Glauciane Viera Damasceno; Juliana Silva Pereira Mendonça; Lucas Dos Santos Silva; Vitor Lopes Chagas; José Manuel Noguera Bazán; Amanda Silva Dos Santos Aliança; Rita de Cássia Mendonça de Miranda; Adrielle Zagmignan; Andrea de Souza Monteiro; Luís Cláudio Nascimento da Silva Journal: Pathogens Date: 2021-02-02
Authors: E Armengol; O Domenech; E Fusté; I Pérez-Guillén; J H Borrell; J M Sierra; M Vinas Journal: Infect Drug Resist Date: 2019-07-11 Impact factor: 4.003
Authors: Charles Omollo; Vinayak Singh; Elizabeth Kigondu; Antonina Wasuna; Pooja Agarwal; Atica Moosa; Thomas R Ioerger; Valerie Mizrahi; Kelly Chibale; Digby F Warner Journal: Antimicrob Agents Chemother Date: 2021-02-22 Impact factor: 5.191