title: In vitro and in vivo activity of meropenem and sulbactam against a multidrug-resistant Acinetobacter baumannii strain.
abstract: OBJECTIVE
  The potential therapeutic role of meropenem combined with sulbactam against a clinical endemic isolate of multidrug-resistant Acinetobacter baumannii, Ab-153, was investigated.
  
  
  METHODS
  The antimicrobial susceptibility of Ab-153 to various drugs was studied by the agar dilution method and Etest strips. The antibacterial activity of meropenem and sulbactam were investigated by a time-kill study in vitro and further examined for therapeutic efficacy in vivo in a murine model.
  
  
  RESULTS
  In the time-kill study, at a concentration of 0.5 x MIC (4 mg/L) of meropenem, 1 x MIC (8 mg/L) of sulbactam and both in combination, only the combination demonstrated bactericidal effects and there was at least a 5 log(10) reduction in bacterial colony counts after 48 h, compared with either drug alone. BALB/c mice infected with 2.1-2.6 x 10(7) cfu of Ab-153 were treated with 20 mg/kg meropenem every 8 h, 40 mg/kg sulbactam every 8 h or both in combination. The survival rate of mice in the combination group was significantly higher than that in the meropenem-treated or sulbactam-treated group (87% versus 35%, P = 0.0004; 87% versus 30%, P = 0.0002).
  
  
  CONCLUSIONS
  Meropenem in conjunction with sulbactam can exhibit more potent antimicrobial activity against Ab-153 than meropenem or sulbactam alone.
authors.affiliation: Department of Medicine, National Cheng Kung University Medical College, Tainan, Taiwan.
authors.forename: Wen-Chien
authors.initials: WC
authors.lastname: Ko
authors.forename: Hsin-Chun
authors.initials: HC
authors.lastname: Lee
authors.forename: Shyh-Ren
authors.initials: SR
authors.lastname: Chiang
authors.forename: Jing-Jou
authors.initials: JJ
authors.lastname: Yan
authors.forename: Jiunn-Jong
authors.initials: JJ
authors.lastname: Wu
authors.forename: Chin-Li
authors.initials: CL
authors.lastname: Lu
authors.forename: Yin-Ching
authors.initials: YC
authors.lastname: Chuang
mesh_terms: D000151:Acinetobacter Infections / Q000188:drug therapy* / Q000382:microbiology; D040981:Acinetobacter baumannii / Q000187:drug effects*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D004338:Drug Combinations; D024901:Drug Resistance, Multiple, Bacterial; D005260:Female; D000077731:Meropenem; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D013407:Sulbactam / Q000494:pharmacology* / Q000627:therapeutic use*; D016019:Survival Analysis; D013845:Thienamycins / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D013845:Thienamycins; D000077731:Meropenem; D013407:Sulbactam