Original Article

Ann Lab Med 2016; 36(2): 124-130

Published online March 1, 2016

Copyright © Korean Society for Laboratory Medicine.

In Vitro Interactions of Antibiotic Combinations of Colistin, Tigecycline, and Doripenem Against Extensively Drug-Resistant and Multidrug-Resistant Acinetobacter baumannii

Gyun Cheol Park, M.D.1, Ji Ae Choi, B.S.2, Sook Jin Jang, M.D.1,2, Seok Hoon Jeong, M.D.3, Choon-Mee Kim, Ph.D.4, In Sun Choi, M.D.1, Seong Ho Kang, M.D.1, Geon Park, M.D.1, and Dae Soo Moon, M.D.1

Department of Laboratory Medicine1, and Research Center for Resistant Cells2, College of Medicine, Chosun University, Gwangju; Department of Laboratory Medicine and Research Institute of Bacterial Resistance3, Yonsei University College of Medicine, Seoul; Premedical Science4, College of Medicine, Chosun University, Gwangju, Korea

Correspondence to: Sook Jin Jang
Department of Laboratory Medicine, College of Medicine, Chosun University, 365 Pilmun-daero, Dong-gu, Gwangju 61453, Korea
Tel: +82-62-220-3259
Fax: +82-62-232-2063

Seok Hoon Jeong
Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, 211 Eonju-ro, Gangnam-gu, Seoul 06273, Korea
Tel: +82-2-2019-3532
Fax: +82-2-2019-4822

Received: July 6, 2015; Revised: October 1, 2015; Accepted: November 11, 2015


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, thedoripenem-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.

Keywords: Extensively drug-resistant, Synergism, Antagonism, Acinetobacter baumannii, Colistin, Doripenem, Tigecycline