Activity of diclofenac used alone and in combination with streptomycin against Mycobacterium tuberculosis in mice
Activity of diclofenac used alone and in combination with streptomycin against Mycobacterium tuberculosis in mice
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DOI：
10.1016/j.ijantimicag.2007.04.016
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发表时间：
2007-10-01
影响因子：
10.8
通讯作者：
Park, Jae-Hak
中科院分区：
文献类型：
--
作者：
Dutta, Noton Kumar;Mazumdar, Kaushiki;Park, Jae-Hak
非甾体抗炎药双氯芬酸（DCL）在体外和体内显示出显著的抗分枝杆菌活性。本研究的目的是确定DCL与一线抗结核抗生素链霉素（STM）联合使用是否能协同增强其体外和小鼠结核感染模型的疗效。测定了该药物对结核杆菌标准株和临床分离株的体外最低抑菌浓度（MIC）和增效作用。瑞士白化病雄性小鼠静脉内感染2.3 × 10（7）M。结核病H37 Rv.用DCL或STM单独以及组合处理小鼠4周，以测定存活率、脾重量和肺和脾中的集落形成单位（CFU）计数。DCL在40 μ g/mL（4x MIC）时对M具有杀菌作用。体外抑菌浓度指数为0.37。从感染后第1天开始，连续4周给予10 μ g/g/天DCL或150 μ g/g/天STM，与未处理动物相比，显著（P < 0.05）降低了细菌计数和平均脾脏重量。与单独接受STM的小鼠相比，同时给予两种药物进一步降低了肺和脾中的CFU计数（P < 0.05）。因此，在这种协同药物对的帮助下，扩展抗生素治疗的能力可能会得到改善，进一步的研究可能会揭示对抗人类多药耐药结核病感染的新方向。(C)2007 Elsevier B. V.和国际化疗学会，版权所有。
The non-steroidal anti - inflammatory drug diclofenac (DCL) shows noteworthy in vitro and in vivo anti mycobacterial activity. The aim of this study was to ascertain whether DCL used in combination with the first-line antitubercular antibiotic streptomycin (STM) synergistically augments its efficacy in vitro as well as in a murine tuberculosis infection model. In vitro minimum inhibitory concentrations (MICs) and synergistic activities of the druls with respect to standard strains and clinical isolates of Alycobacterium tuberculosis we, re determined. Swiss albino male mice were intravenously infected with 2.3 x 10(7) M. tuberculosis H37Rv. Mice were treated with DCL or STM alone as well as in combination for 4 weeks to determine the Survival rate, spleen weight and colony-forming unit (CFU) counts in the lungs and spleen. DCL was bactericidal at 40 mu g/mL (4x MIC) against M. tuberculosis H37Rv and was synergistic with STM in vitro (fractional inhibitory concentration index 0.37). A dose of 10 mu g/g/day DCL or 150 mu g/g/day STM for 4 weeks, administered from I day post infection, significantly (P < 0.05) lowered bacterial counts and reduced mean spleen weight of mice compared with untreated animals. Simultaneous administration of both agents further decreased CFU counts (P < 0.05) in the lungs and spleen compared with mice receiving STM alone. Thus, the ability of extended antibiotic therapy may be improved with the help of this synergistic drug pair in murine tuberculosis, and further investigations may throw light on new directions to combat multidrug-resistant tuberculosis infections in humans. (C) 2007 Elsevier B.V. and the International Society of Chemotherapy, All rights reserved.