Gatifloxacin in combination with rifampicin in a murine tuberculosis model.
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.
Cynamon
Michael
M
Veterans Affairs Medical Center, 800 Irving Avenue, Syracuse, NY 13210, USA. michael.cynamon@med.va.gov
Sklaney
Mary R
MR
Shoen
Carolyn
C
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
D000900:Anti-Bacterial Agents; D000904:Antibiotics, Antitubercular; D000995:Antitubercular Agents; D004338:Drug Combinations; D024841:Fluoroquinolones; D000077734:Gatifloxacin; D007538:Isoniazid; D012293:Rifampin