title: Antimicrobial activity of the imipenem/rifampicin combination against clinical isolates of Acinetobacter baumannii grown in planktonic and biofilm cultures.
abstract: To investigate the antimicrobial activity of imipenem and rifampicin alone and in combination against clinical isolates of Acinetobacter baumannii grown in planktonic and biofilm cultures. Minimum inhibitory concentrations were determined for each isolate grown in suspension and in biofilm using a microbroth dilution method. Chequerboard assays and the agar disk diffusion assay were used to determine synergistic, indifferent or antagonistic interactions between imipenem and rifampicin. We used the tissue culture plate method for A. baumannii biofilm formation to measure the percentage of biofilm inhibition and the amount of extracellular DNA after the treatment. To understand the synergistic mechanisms, we conducted hydroxyl radical formation assays. The results were verified by confocal laser scanning microscopy. Imipenem and rifampicin showed effective antimicrobial activity against suspensions and biofilm cultures of A. baumannii, respectively. Synergistic antimicrobial effects between imipenem and rifampicin were observed in 13 and 17 of the 20 clinical isolates when in suspension and in biofilms, respectively. Imipenem and rifampicin alone and in combination generated hydroxyl radicals, which are highly reactive oxygen forms and the major components of bactericidal agents. Furthermore, treatment with imipenem and rifampicin individually or in combination has obvious antibiofilm effects. The synergistic activity of imipenem and rifampicin against clinical isolates of A. baumannii (in suspension and in biofilms) was observed in vitro. Therefore, we conclude that imipenem combined with rifampicin has the potential to be used as a combinatorial therapy for the treatment of infectious diseases caused by A. baumannii.
authors.affiliation: Department of Infectious Diseases, First Hospital of Jilin University, Key Laboratory for Zoonosis Research, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun, 130062, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Wanguo
authors.initials: W
authors.lastname: Bao
authors.forename: Na
authors.initials: N
authors.lastname: Guo
authors.forename: Haiying
authors.initials: H
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Cheng
authors.forename: Kunqi
authors.initials: K
authors.lastname: Jin
authors.forename: Fengge
authors.initials: F
authors.lastname: Shen
authors.forename: Jiancheng
authors.initials: J
authors.lastname: Xu
authors.forename: Qiaoli
authors.initials: Q
authors.lastname: Zhang
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.forename: Yanan
authors.initials: Y
authors.lastname: An
authors.forename: Kaiyu
authors.initials: K
authors.lastname: Zhang
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Lu
authors.initials: L
authors.lastname: Yu
mesh_terms: D000151:Acinetobacter Infections / Q000382:microbiology; D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000302:isolation & purification / Q000502:physiology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D004347:Drug Interactions; D006801:Humans; D017665:Hydroxyl Radical / Q000032:analysis; D015378:Imipenem / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D018613:Microscopy, Confocal; D012293:Rifampin / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D017665:Hydroxyl Radical; D015378:Imipenem; D012293:Rifampin