title: In Vitro Interactions of Antibiotic Combinations of Colistin, Tigecycline, and Doripenem Against Extensively Drug-Resistant and Multidrug-Resistant Acinetobacter baumannii.
abstract: BACKGROUND
  Acinetobacter baumannii infections are difficult to treat owing to the emergence of various antibiotic resistant isolates. Because treatment options are limited for multidrug-resistant (MDR) A. baumannii infection, the discovery of new therapies, including combination therapy, is required. We evaluated the synergistic activity of colistin, doripenem, and tigecycline combinations against extensively drug-resistant (XDR) A. baumannii and MDR A. baumannii.
  
  
  METHODS
  Time-kill assays were performed for 41 XDR and 28 MDR clinical isolates of A. baumannii by using colistin, doripenem, and tigecycline combinations. Concentrations representative of clinically achievable levels (colistin 2 μg/mL, doripenem 8 μg/mL) and achievable tissue levels (tigecycline 2 μg/mL) for each antibiotic were used in this study.
  
  
  RESULTS
  The colistin-doripenem combination displayed the highest rate of synergy (53.6%) and bactericidal activity (75.4%) in 69 clinical isolates of A. baumannii. Among them, the-doripenem-tigecycline combination showed the lowest rate of synergy (14.5%) and bactericidal activity (24.6%). The doripenem-tigecycline combination showed a higher antagonistic interaction (5.8%) compared with the colistin-tigecycline (1.4%) combination. No antagonism was observed for the colistin-doripenem combination.
  
  
  CONCLUSIONS
  The colistin-doripenem combination is supported in vitro by the high rate of synergy and bactericidal activity and lack of antagonistic reaction in XDR and MDR A. baumannii. It seems to be necessary to perform synergy tests to determine the appropriate combination therapy considering the antagonistic reaction found in several isolates against the doripenem-tigecycline and colistin-tigecycline combinations. These findings should be further examined in clinical studies.
authors.affiliation: Department of Laboratory Medicine, College of Medicine, Chosun University, Gwangju, Korea.
authors.forename: Gyun Cheol
authors.initials: GC
authors.lastname: Park
authors.affiliation: Research Center for Resistant Cells, College of Medicine, Chosun University, Gwangju, Korea.
authors.forename: Ji Ae
authors.initials: JA
authors.lastname: Choi
authors.affiliation: Department of Laboratory Medicine, College of Medicine, Chosun University, Gwangju, Korea.|Research Center for Resistant Cells, College of Medicine, Chosun University, Gwangju, Korea. sjbjang@chosun.ac.kr.
authors.forename: Sook Jin
authors.initials: SJ
authors.lastname: Jang
authors.affiliation: Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, Korea. kscpjsh@yuhs.ac.
authors.forename: Seok Hoon
authors.initials: SH
authors.lastname: Jeong
authors.affiliation: Premedical Science, College of Medicine, Chosun University, Gwangju, Korea.
authors.forename: Choon-Mee
authors.initials: CM
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, College of Medicine, Chosun University, Gwangju, Korea.
authors.forename: In Sun
authors.initials: IS
authors.lastname: Choi
authors.affiliation: Department of Laboratory Medicine, College of Medicine, Chosun University, Gwangju, Korea.
authors.forename: Seong Ho
authors.initials: SH
authors.lastname: Kang
authors.affiliation: Department of Laboratory Medicine, College of Medicine, Chosun University, Gwangju, Korea.
authors.forename: Geon
authors.initials: G
authors.lastname: Park
authors.affiliation: Department of Laboratory Medicine, College of Medicine, Chosun University, Gwangju, Korea.
authors.forename: Dae Soo
authors.initials: DS
authors.lastname: Moon
mesh_terms: D000151:Acinetobacter Infections / Q000188:drug therapy / Q000382:microbiology; D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000235:genetics; D015780:Carbapenems / Q000494:pharmacology* / Q000627:therapeutic use; D003091:Colistin / Q000494:pharmacology* / Q000627:therapeutic use; D000077726:Doripenem; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006801:Humans; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D058885:Multilocus Sequence Typing; D000078304:Tigecycline; D001618:beta-Lactamases / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015780:Carbapenems; D000078304:Tigecycline; D000077726:Doripenem; D001618:beta-Lactamases; C063912:carbapenemase; D008911:Minocycline; D003091:Colistin
keywords: Acinetobacter baumannii; Antagonism; Colistin; Doripenem; Extensively drug-resistant; Synergism; Tigecycline