title: Sulfamethoxazole enhances the antimycobacterial activity of rifampicin.
abstract: OBJECTIVE
  To investigate the effect of trimethoprim/sulfamethoxazole on the survival of Mycobacterium tuberculosis and trimethoprim and sulfamethoxazole individually and combined with the first-line tuberculosis drugs (isoniazid, rifampicin and ethambutol).
  
  
  METHODS
  M. tuberculosis strains were exposed to either trimethoprim/sulfamethoxazole combination or sulfamethoxazole and trimethoprim alone at various concentrations. The strains were also exposed to sulfamethoxazole in combination with existing antibiotics to assess the combined effect on the growth of M. tuberculosis in the BACTEC 460TB system. The effect of the drugs was compared with vehicle-treated controls. Drug interactions were interpreted using quotient values obtained from the growth index of cultures treated with a single drug or the combination.
  
  
  RESULTS
  Trimethoprim showed a negligible effect on the growth of M. tuberculosis while sulfamethoxazole inhibited 80% of the growth of M. tuberculosis at 4.75 mg/L. There was no synergistic activity between sulfamethoxazole and trimethoprim, although an additive effect was observed. A statistically significant synergistic effect was observed between sulfamethoxazole and rifampicin. Sulfamethoxazole also had an additive effect with ethambutol, but there was no interaction with isoniazid.
  
  
  CONCLUSIONS
  Sulfamethoxazole is the main active compound against M. tuberculosis in the combination trimethoprim/sulfamethoxazole and has a synergistic effect with rifampicin. These findings suggest that sulfamethoxazole has potential in the multidrug regimen against M. tuberculosis.
authors.affiliation: DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, MRC Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences,  Stellenbosch University, PO Box 19063/Francie van Zijl Drive, Tygerberg 7505,  South Africa.
authors.forename: Lubabalo
authors.initials: L
authors.lastname: Macingwana
authors.forename: Bienyameen
authors.initials: B
authors.lastname: Baker
authors.forename: Andile H
authors.initials: AH
authors.lastname: Ngwane
authors.forename: Catriona
authors.initials: C
authors.lastname: Harper
authors.forename: Mark F
authors.initials: MF
authors.lastname: Cotton
authors.forename: Anneke
authors.initials: A
authors.lastname: Hesseling
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Diacon
authors.forename: Paul
authors.initials: P
authors.lastname: van Helden
authors.forename: Ian
authors.initials: I
authors.lastname: Wiid
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D004357:Drug Synergism; D004977:Ethambutol / Q000494:pharmacology; D007538:Isoniazid / Q000494:pharmacology; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D012293:Rifampin / Q000494:pharmacology*; D013420:Sulfamethoxazole / Q000494:pharmacology*; D014295:Trimethoprim / Q000494:pharmacology
chemical_list: D000995:Antitubercular Agents; D004977:Ethambutol; D014295:Trimethoprim; D013420:Sulfamethoxazole; D007538:Isoniazid; D012293:Rifampin