title: Gatifloxacin in combination with rifampicin in a murine tuberculosis model.
abstract: OBJECTIVE
  Gatifloxacin previously demonstrated good in vitro and in vivo activities against Mycobacterium tuberculosis. Several regimens of gatifloxacin in combination with rifampicin were compared with isoniazid plus rifampicin in a mouse tuberculosis model.
  
  
  METHODS
  C57BL/6 mice were infected intranasally with approximately 10(6) viable M. tuberculosis organisms. Treatment with various regimens of gatifloxacin plus rifampicin was started 1 week post-infection and was administered for 4-12 weeks. Mice were euthanized at the end of therapy and their right lungs were removed and cell counts were determined.
  
  
  RESULTS
  Gatifloxacin 100 mg/kg plus rifampicin 10 mg/kg has activity similar to that of isoniazid plus rifampicin in the 12 week treatment model. Gatifloxacin 300 mg/kg plus rifampicin 20 mg/kg yields a non-cultivatable state after 12 weeks of therapy and approaches but does not achieve a durable cure.
  
  
  CONCLUSIONS
  Gatifloxacin in combination with rifampicin is a promising combination for potential evaluation in human clinical trials. Gatifloxacin plus rifampicin regimens had activities similar to or better than isoniazid plus rifampicin. A quinolone plus rifampicin combination may provide the foundation for shorter course regimens than the current isoniazid plus rifampicin-based regimen.
authors.affiliation: Veterans Affairs Medical Center, 800 Irving Avenue, Syracuse, NY 13210, USA. michael.cynamon@med.va.gov
authors.forename: Michael
authors.initials: M
authors.lastname: Cynamon
authors.forename: Mary R
authors.initials: MR
authors.lastname: Sklaney
authors.forename: Carolyn
authors.initials: C
authors.lastname: Shoen
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000904:Antibiotics, Antitubercular / Q000627:therapeutic use*; D000995:Antitubercular Agents / Q000627:therapeutic use; D015169:Colony Count, Microbial; D004338:Drug Combinations; D005260:Female; D024841:Fluoroquinolones / Q000627:therapeutic use*; D000077734:Gatifloxacin; D007538:Isoniazid / Q000627:therapeutic use; D008168:Lung / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D012293:Rifampin / Q000627:therapeutic use*; D014376:Tuberculosis / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D000904:Antibiotics, Antitubercular; D000995:Antitubercular Agents; D004338:Drug Combinations; D024841:Fluoroquinolones; D000077734:Gatifloxacin; D007538:Isoniazid; D012293:Rifampin