OBJECTIVES: 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.
OBJECTIVES: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 mousetuberculosis 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: Gillian L Beamer; Joshua Cyktor; David K Flaherty; Paul C Stromberg; Bridget Carruthers; Joanne Turner Journal: Eur J Immunol Date: 2012-04 Impact factor: 5.532
Authors: Jossy van den Boogaard; Gibson S Kibiki; Elton R Kisanga; Martin J Boeree; Rob E Aarnoutse Journal: Antimicrob Agents Chemother Date: 2008-12-15 Impact factor: 5.191
Authors: Wynand Smythe; Corinne S Merle; Roxana Rustomjee; Martin Gninafon; Mame Bocar Lo; Oumou Bah-Sow; Piero L Olliaro; Christian Lienhardt; John Horton; Peter Smith; Helen McIlleron; Ulrika S H Simonsson Journal: Antimicrob Agents Chemother Date: 2013-06-17 Impact factor: 5.191