title: Activity of gatifloxacin alone or in combination with pyrimethamine or gamma interferon against Toxoplasma gondii.
abstract: The activity of gatifloxacin against Toxoplasma gondii, either alone or in combination with pyrimethamine or gamma interferon (IFN-gamma), was examined in vitro and in vivo. In vitro, gatifloxacin significantly inhibited intracellular replication of tachyzoites of the RH strain with a 50% inhibitory concentration of 0.21 microg/ml at 48 h after addition of the drug to the cultures. Toxicity for host cells was not observed at this concentration. A synergistic effect (combination indices < 0.5) was demonstrated in vitro following 48 h of treatment with the combination of gatifloxacin and pyrimethamine (1:1 ratio). Doses of gatifloxacin of 100 and 200 mg/kg of body weight/day administered orally to mice for 10 days resulted in significant (P values of 0.056 and <0.0001, respectively) prolongation in time to death following infection with a lethal inoculum of tachyzoites. A dose of 400 mg/kg resulted in 20% survival (P = 0.0001). Mortality was 100% in untreated control mice and in mice treated with 25 or 50 mg/kg/day. Treatment of infected mice with a combination of gatifloxacin at 200 mg/kg/day and pyrimethamine at 12.5 mg/kg/day resulted in 85% survival, whereas 100 and 80% of mice treated with gatifloxacin alone or pyrimethamine alone, respectively, died (P < 0.0001). Moreover, a gatifloxacin dose of 200 mg/kg/day administered orally for 10 days plus 2 microg of recombinant murine IFN-gamma/day administered intraperitoneally for 10 days resulted in significant survival compared with IFN-gamma alone (P < 0.0001) or gatifloxacin alone (P < 0.007).
authors: Department of Immunology and Infectious Diseases, Research Institute, Palo Alto Medical Foundation, Palo Alto, California 94301, USA.
authors: A A
authors: AA
authors: Khan
authors: T R
authors: TR
authors: Slifer
authors: F G
authors: FG
authors: Araujo
authors: J S
authors: JS
authors: Remington
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D024841:Fluoroquinolones; D000077734:Gatifloxacin; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D011739:Pyrimethamine / Q000494:pharmacology* / Q000627:therapeutic use; D011994:Recombinant Proteins; D014122:Toxoplasma / Q000187:drug effects*; D014123:Toxoplasmosis / Q000188:drug therapy / Q000382:microbiology
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D011994:Recombinant Proteins; D007371:Interferon-gamma; D000077734:Gatifloxacin; D011739:Pyrimethamine