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

Authors
 Gyun Cheol Park  ;  Ji Ae Choi  ;  Sook Jin Jang  ;  Seok Hoon Jeong  ;  Choon-Mee Kim  ;  In Sun Choi  ;  Seong Ho Kang  ;  Geon Park  ;  Dae Soo Moon 
Citation
 Annals of Laboratory Medicine, Vol.36(2) : 124-130, 2016 
Journal Title
 Annals of Laboratory Medicine 
ISSN
 2234-3806 
Issue Date
2016
MeSH
Acinetobacter Infections/drug therapy ; Acinetobacter Infections/microbiology ; Acinetobacter baumannii/drug effects* ; Acinetobacter baumannii/genetics ; Acinetobacter baumannii/isolation & purification ; Anti-Bacterial Agents/pharmacology* ; Anti-Bacterial Agents/therapeutic use ; Bacterial Proteins/genetics ; Carbapenems/pharmacology* ; Carbapenems/therapeutic use ; Colistin/pharmacology* ; Colistin/therapeutic use ; Drug Resistance, Multiple, Bacterial/drug effects* ; Drug Synergism ; Drug Therapy, Combination ; Humans ; Microbial Sensitivity Tests ; Minocycline/analogs & derivatives* ; Minocycline/pharmacology ; Minocycline/therapeutic use ; Multilocus Sequence Typing ; beta-Lactamases/genetics
Keywords
Acinetobacter baumannii ; Antagonism ; Colistin ; Doripenem ; Extensively drug-resistant ; Synergism ; Tigecycline
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.
DOI
10.3343/alm.2016.36.2.124
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
Yonsei Authors
정석훈(Jeong, Seok Hoon) ORCID logo https://orcid.org/0000-0001-9290-897X
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/151681
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