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多黏菌素与替加环素或利福平联合对多重耐药嗜麦芽窄食单胞菌的活性。

Activity of colistin in combination with tigecycline or rifampicin against multidrug-resistant Stenotrophomonas maltophilia.

机构信息

Antimicrobial Research Group, Centre for Immunology and Infectious Disease, Blizard Institute, Queen Mary, University of London, Blizard Building, 4 Newark Street, Whitechapel, London, E1 2AT, UK.

出版信息

Eur J Clin Microbiol Infect Dis. 2014 Sep;33(9):1565-72. doi: 10.1007/s10096-014-2101-3. Epub 2014 Apr 30.

Abstract

The antimicrobial treatment of Stenotrophomonas maltophilia infections is complicated by intrinsic multidrug resistance and a lack of reliable susceptibility data. We assessed the activity of colistin (COL), rifampicin (RIF) and tigecycline (TGC) alone and in combination using a range of in vitro susceptibility testing methodologies and a simple invertebrate model of S. maltophilia infection (Galleria mellonella). Synergy [fractional inhibitory concentration indices (FICIs) ≤0.5] between COL and either RIF or TGC was observed against 92 % and 88 % of 25 S. maltophilia isolates, respectively, despite resistance to one or another of the single agents alone. In time-kill assays, COL combined with either RIF or TGC was superior to single agents, but only the COL/RIF regimen was reliably bactericidal. The in vitro findings correlated with treatment outcomes in G. mellonella, with heightened survival observed for larvae treated with COL/RIF or COL/TGC compared with COL, RIF or TGC alone. COL combined with RIF was the most effective combination overall in both in vitro and in vivo (p < 0.05) assays. Given the difficulty in selecting appropriate therapy for S. maltophilia infections, regimens consisting of COL combined with RIF or TGC could be considered for clinical use.

摘要

嗜麦芽窄食单胞菌感染的抗菌治疗因固有多重耐药性和缺乏可靠的药敏数据而变得复杂。我们使用一系列体外药敏检测方法和简单的嗜麦芽窄食单胞菌感染(家蚕)体外模型评估了多粘菌素(COL)、利福平(RIF)和替加环素(TGC)单独及联合用药的活性。尽管单独使用一种药物时存在耐药性,但 COL 与 RIF 或 TGC 之间的协同作用(抑菌浓度指数(FICI)≤0.5)分别观察到针对 25 株嗜麦芽窄食单胞菌分离株中的 92%和 88%。在时间杀伤试验中,COL 与 RIF 或 TGC 联合使用优于单一药物,但只有 COL/RIF 方案具有可靠的杀菌作用。体外研究结果与家蚕的治疗结果相关,与单独使用 COL、RIF 或 TGC 相比,用 COL/RIF 或 COL/TGC 治疗的幼虫存活率更高。在体外和体内(p<0.05)试验中,COL 联合利福平总体上是最有效的组合。鉴于选择嗜麦芽窄食单胞菌感染的适当治疗方案存在困难,因此可以考虑将 COL 联合利福平或替加环素的方案用于临床。

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