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替加环素对创伤弧菌的体外和体内抗菌活性。

In vitro and in vivo antibacterial activity of tigecycline against Vibrio vulnificus.

机构信息

Department of Medicine, Chi Mei Medical Center, Tainan, Taiwan; Department of Health and Nutrition, Chia Nan University of Pharmacy & Science, Tainan, Taiwan.

Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan.

出版信息

J Microbiol Immunol Infect. 2018 Feb;51(1):76-81. doi: 10.1016/j.jmii.2016.04.009. Epub 2016 May 13.

Abstract

BACKGROUND/PURPOSE: The aim of this study is to investigate the role of tigecycline in Vibrio vulnificus infection.

METHODS

Eight randomly selected clinical V. vulnificus isolates were studied to obtain the minimal inhibitory concentrations (MICs) of minocycline, cefotaxime, and tigecycline, and the time-kill curves of tigecycline alone or in combination with other drugs. A peritonitis mouse model was used for the evaluation of the therapeutic efficacy of tigecycline alone or cefotaxime in combination with minocycline or tigecycline.

RESULTS

The MIC of minocycline, cefotaxime, and tigecycline for eight clinical V. vulnificus isolates was 0.06-0.12 μg/mL, 0.03-0.06 μg/mL, and 0.03-0.06 μg/mL, respectively. In time-killing studies, at the concentration of 1 × MIC, the inhibitory effect of tigecycline persisted for 24 hours in five of eight isolates. With 2 × MIC and trough level, the inhibitory effect was noted in all isolates for 24 hours. With the combination of minocycline plus cefotaxime and tigecycline plus cefotaxime at 1/2 × MIC, the bactericidal effect was noted in 25% and 62.5% of eight isolates and synergism in 50% and 75% of isolates. With a low (1.25 × 10 CFU/mL) inoculum, all infected mice survived with tigecycline alone, tigecycline plus cefotaxime, or minocycline plus cefotaxime on the 14 day. At the inoculum of 1.25 × 10 CFU, the survival rate was 33.3% on the 14 day in the tigecycline plus cefotaxime-treated group, but none of the mice treated by tigecycline alone or minocycline plus cefotaxime survived (33.3% vs. 0%, p = 0.01 by Fisher's exact test).

CONCLUSION

Our in vitro combination and animal studies indicate that tigecycline could be an option for the treatment of invasive V. vulnificus infections.

摘要

背景/目的:本研究旨在探讨替加环素在创伤弧菌感染中的作用。

方法

研究了 8 株随机选择的临床创伤弧菌分离株,以获得米诺环素、头孢噻肟和替加环素的最小抑菌浓度(MIC),以及替加环素单独或联合其他药物的杀菌曲线。采用腹膜炎小鼠模型评估替加环素单独或头孢噻肟联合米诺环素或替加环素的治疗效果。

结果

8 株临床创伤弧菌分离株的米诺环素、头孢噻肟和替加环素 MIC 分别为 0.06-0.12μg/ml、0.03-0.06μg/ml 和 0.03-0.06μg/ml。在杀菌试验中,在 1×MIC 浓度下,替加环素对 8 株分离株中的 5 株的抑制作用持续 24 小时。在 2×MIC 和谷浓度下,所有分离株在 24 小时内均有抑制作用。米诺环素加头孢噻肟和替加环素加头孢噻肟联合应用时,MIC 的 1/2× 对 8 株分离株中的 25%有杀菌作用,50%有协同作用,MIC 的 1/2× 对 8 株分离株中的 62.5%有杀菌作用,75%有协同作用。用低(1.25×10 CFU/ml)接种物,单独用替加环素、替加环素加头孢噻肟或米诺环素加头孢噻肟治疗的所有感染小鼠在第 14 天存活。在 1.25×10 CFU 的接种物下,替加环素加头孢噻肟治疗组第 14 天的存活率为 33.3%,而单独用替加环素或米诺环素加头孢噻肟治疗的小鼠均未存活(33.3%比 0%,Fisher 精确检验,p=0.01)。

结论

我们的体外联合和动物研究表明,替加环素可能是治疗侵袭性创伤弧菌感染的一种选择。

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