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

Noton Kumar Dutta, Kaushiki Mazumdar, Sujata G. Dastidar, Jae Hak Park

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)336-340
Number of pages5
JournalInternational Journal of Antimicrobial Agents
Volume30
Issue number4
DOIs
StatePublished - Oct 1 2007
Externally publishedYes

Keywords

  • Antimycobacterial agents
  • Diclofenac
  • In vivo
  • Streptomycin
  • Synergism
  • Tuberculosis

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

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