Intra- and extracellular activities of trimethoprim-sulfamethoxazole against susceptible and multidrug-resistant Mycobacterium tuberculosis

Antimicrob Agents Chemother. 2014 Dec;58(12):7557-9. doi: 10.1128/AAC.02995-14. Epub 2014 Sep 22.

Abstract

We investigated the activity of trimethoprim-sulfamethoxazole (SXT) against Mycobacterium tuberculosis, the pathogen that causes tuberculosis (TB). The MIC distribution of SXT was 0.125/2.4 to 2/38 mg/liter for the 100 isolates tested, including multi- and extensively drug-resistant isolates (MDR/XDR-TB), whereas the intracellular MIC90 of sulfamethoxazole (SMX) for the pansusceptible strain H37Rv was 76 mg/liter. In an exploratory analysis using a ratio of the unbound area under the concentration-time curve from 0 to 24 h over MIC (fAUC0-24/MIC) using ≥ 25 as a potential target, the cumulative fraction response was ≥ 90% at doses of ≥ 2,400 mg of SMX. SXT is a potential treatment option for MDR/XDR-TB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitubercular Agents / pharmacology*
  • Cell Line
  • Drug Resistance, Multiple, Bacterial / drug effects*
  • Gene Expression
  • Genes, Reporter
  • Humans
  • Luciferases / genetics
  • Luciferases / metabolism
  • Macrophages / drug effects
  • Macrophages / microbiology
  • Microbial Sensitivity Tests
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / genetics
  • Mycobacterium tuberculosis / growth & development
  • Trimethoprim, Sulfamethoxazole Drug Combination / pharmacology*
  • Tuberculosis, Multidrug-Resistant / microbiology

Substances

  • Antitubercular Agents
  • Trimethoprim, Sulfamethoxazole Drug Combination
  • Luciferases