The efficacy of
atovaquone (ATO) combined with
clindamycin (CLI) against Toxoplasma gondii was examined in murine models of
infection with a mouse-non-virulent (Me49) strain. Swiss-Webster mice inoculated by mouth with 10 or 20
cysts were treated with ATO and CLI alone or combined at dosages of ATO 5-100 and CLI 25-400 mg/kg/day for 2-4 weeks. Drug treatment was initiated (i) day 4 post-
infection (acute
infection), (ii) 3 months post-
infection (chronic infection) and (iii) following a 2-3 week course of treatment with
dexamethasone (DXM) alone or combined with
cortisone-acetate (CA) introduced 3 months post-
infection (reactivated toxoplasmosis). In acute
infection, whereas treatment with any drug or
drug combination significantly enhanced survival and reduced the brain
cyst burden, in mice treated with ATO alone or combined with CLI, the
cyst counts were significantly lower than in mice treated with CLI alone. In
chronic infection, the decrease in the
cyst burden observed 2 weeks
after treatment with either drug alone was significant only in mice treated with the combined drugs. Most importantly, in reactivated
toxoplasmosis, whereas an effect for the combined drugs was shown in mice suppressed with both DXM alone and combined with CA, in mice pre-treated with DXM a 3 week course of ATO > or = 25 and CLI 50 mg/kg/day significantly increased survival and markedly decreased the
cyst burden. The latter effect was long-term, since the
cyst burdens in treated mice continued to decrease up to 3 months later, whereas they increased in the untreated mice. The results warrant clinical evaluation of the combination of ATO and CLI in the treatment of
toxoplasmosis in both immunocompetent and, more importantly, immunosuppressed patients.