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

Lina Davies ForsmanT SchönU S H SimonssonJ BruchfeldM LarssonP JuréenE SturegårdC G GiskeK Ängeby
Published in: Antimicrobial agents and chemotherapy (2014)
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.
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