title: In vitro antimicrobial synergy of colistin with rifampicin and carbapenems against colistin-resistant Acinetobacter baumannii clinical isolates.
abstract: Increased use of colistin in a clinical setting had resulted in the emergence of colistin-resistant (CoR) Acinetobacter baumannii. Combination therapy has been studied as a new approach to treat infections caused by A. baumannii. Here, we investigated the in vitro antimicrobial synergistic activities of several antimicrobial agent combinations against CoR A. baumannii. A total of 41 non-duplicate clinical isolates of CoR A. baumannii from a tertiary care hospital in Korea were prospectively collected from April 2012 to December 2014. As a control group, 41 carbapenem-resistant but colistin-susceptible (CoS) A. baumannii strains were also evaluated. Minimum inhibitory concentrations (MICs) of antimicrobial agents were determined by Etest in triplicate, and in vitro synergy tests were performed by the Etest MIC:MIC ratio method. Synergistic activity was determined as the sum of each antimicrobial agent's fractional inhibitory concentration evaluated (ΣFIC): synergy, ≤0.5; indifference, >0.5-4; and antagonism, >4. Synergistic activities were more frequently observed in the CoR group than the CoS group for combinations of colistin-rifampicin (80.5% vs. 14.6%, P< 0.0001), colistin-meropenem (85.4% vs. 4.9%, P< 0.0001), and colistin-imipenem (46.3% vs. 2.4%, P< 0.0001). Combination with rifampicin or meropenem lowered colistin MICs against CoR A. baumannii clinical isolates to the susceptible range (≤ 2 μg/mL) more frequently (61.0%, 25/41, both) than combination with imipenem (29.3%, 12/41). Clinical trials are needed to prove the in vivo efficacy of those antimicrobial combinations that exhibited significant in vitro antimicrobial synergistic effects against CoR A. baumannii.
authors.affiliation: Department of Laboratory Medicine, Eone Reference Laboratory, Incheon, Seoul, Republic of Korea; Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Duck Jin
authors.initials: DJ
authors.lastname: Hong
authors.affiliation: Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jung Ok
authors.initials: JO
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hyukmin
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Eun-Jeong
authors.initials: EJ
authors.lastname: Yoon
authors.affiliation: Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: kscpjsh@yuhs.ac.
authors.forename: Seok Hoon
authors.initials: SH
authors.lastname: Jeong
authors.affiliation: Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Dongeun
authors.initials: D
authors.lastname: Yong
authors.affiliation: Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Kyungwon
authors.initials: K
authors.lastname: Lee
mesh_terms: D000151:Acinetobacter Infections / Q000382:microbiology*; D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000302:isolation & purification; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015780:Carbapenems / Q000494:pharmacology*; D003091:Colistin / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D004357:Drug Synergism; D006801:Humans; D008826:Microbial Sensitivity Tests; D011446:Prospective Studies; D056910:Republic of Korea; D012293:Rifampin / Q000494:pharmacology*; D062606:Tertiary Care Centers
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D012293:Rifampin; D003091:Colistin
keywords: Acinetobacter baumannnii; Colistin; Combination; Meropenem; Rifampicin; Synergism