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Activity of diclofenac used alone and in combination with streptomycin against Mycobacterium tuberculosis in mice

Cited 55 time in Web of Science Cited 61 time in Scopus
Authors
Dutta, Noton Kumar; Mazumdar, Kaushiki; Dastidar, Sujata G.; Park, Jae Hak
Issue Date
2007-07-17
Publisher
Elsevier
Citation
J Antimicrob Agents 2007;30:336-340
Keywords
TuberculosisAntimycobacterial agentsDiclofenacStreptomycinSynergismIn vivo
Abstract
The non-steroidal anti-inflammatory drug diclofenac (DCL) shows noteworthy in vitro and in vivo antimycobacterial 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 drugs with respect to standard strains and clinical isolates of Mycobacterium tuberculosis were determined. Swiss albino male mice were intravenously infected with 2.3 × 107 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 μg/mL (4× MIC) against M. tuberculosis H37Rv and was synergistic with STM in vitro (fractional inhibitory concentration index 0.37). A dose of 10 μg/g/day DCL or 150 μg/g/day STM for 4 weeks, administered from 1 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.
ISSN
0924-8579
Language
English
URI
http://hdl.handle.net/10371/7397
DOI
https://doi.org/10.1016/j.ijantimicag.2007.04.016
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
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