title: Synergistic efficacy of meropenem and rifampicin in a murine model of sepsis caused by multidrug-resistant Acinetobacter baumannii.
abstract: Multidrug-resistant Acinetobacter baumannii becomes an increasing challenge due to the overuse of antibiotics. Combination therapies are considered as effective options to overcome this matter. The present study was to investigate the synergistic activity of meropenem combined with other antibiotics in vitro and in vivo. Checkerboard assay and time-kill assay were performed to study the combination effects in vitro. For the animal model, a murine sepsis model injected with inoculums intraperitoneally was used. Susceptibility test showed that all the twelve strains in this study were resistant to most of the antibiotics except rifampicin. In combination, meropenem plus rifampicin exhibited synergistic activity against six of twelve strains. In the sepsis model, meropenem monotherapy had no therapeutic effect in this model while it can enhance the activity of rifampicin in both survival rate and bacterial clearance from blood. Moreover, combination therapy significantly reduced plasma IL-6 levels compared with rifampicin monotherapy. Pharmacokinetic analysis of rifampicin was also performed in this study. These data above showed that there was synergistic activity between meropenem and rifampicin against multidrug-resistant Acinetobacter baumannii both in vitro and for experimental model of sepsis. It suggested that combining meropenem with rifampicin may be appropriate in treating multidrug-resistant Acinetobacter baumannii infections.
authors.affiliation: Department of Pharmacy, Xijing Hospital of the Fourth Military Medical University, 127 Changlexi Street, Xi׳an 710032, Shaanxi, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Pharmacy, Xijing Hospital of the Fourth Military Medical University, 127 Changlexi Street, Xi׳an 710032, Shaanxi, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Xijing Hospital of the Fourth Military Medical University, 127 Changlexi Street, Xi׳an 710032, Shaanxi, China.
authors.forename: Jiankang
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pharmacy, Xijing Hospital of the Fourth Military Medical University, 127 Changlexi Street, Xi׳an 710032, Shaanxi, China.
authors.forename: Chongbo
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Pharmacy, Xijing Hospital of the Fourth Military Medical University, 127 Changlexi Street, Xi׳an 710032, Shaanxi, China.
authors.forename: Jinyi
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Pharmacy, Xijing Hospital of the Fourth Military Medical University, 127 Changlexi Street, Xi׳an 710032, Shaanxi, China.
authors.forename: Meiyou
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, Xijing Hospital of the Fourth Military Medical University, 127 Changlexi Street, Xi׳an 710032, Shaanxi, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Xijing Hospital of the Fourth Military Medical University, 127 Changlexi Street, Xi׳an 710032, Shaanxi, China.
authors.forename: Chengtao
authors.initials: C
authors.lastname: Lu
authors.affiliation: Department of Pharmacy, Xijing Hospital of the Fourth Military Medical University, 127 Changlexi Street, Xi׳an 710032, Shaanxi, China.
authors.forename: Gangwei
authors.initials: G
authors.lastname: Shang
authors.affiliation: Department of Pharmacy, Xijing Hospital of the Fourth Military Medical University, 127 Changlexi Street, Xi׳an 710032, Shaanxi, China. Electronic address: jiayanyan-2004@hotmail.com.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Department of Pharmacy, Xijing Hospital of the Fourth Military Medical University, 127 Changlexi Street, Xi׳an 710032, Shaanxi, China. Electronic address: adwen-2004@hotmail.com.
authors.forename: Aidong
authors.initials: A
authors.lastname: Wen
mesh_terms: D000151:Acinetobacter Infections / Q000097:blood / Q000188:drug therapy; D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects* / Q000502:physiology; D004357:Drug Synergism; D006801:Humans; D008297:Male; D000077731:Meropenem; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests / Q000379:methods; D012293:Rifampin / Q000008:administration & dosage*; D018805:Sepsis / Q000097:blood / Q000188:drug therapy*; D013845:Thienamycins / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D013845:Thienamycins; D000077731:Meropenem; D012293:Rifampin
keywords: Acinetobacter baumannii; Combination; Meropenem; Murine sepsis model; Rifampicin