JAC Advance Access originally published online on November 18, 2002
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Journal of Antimicrobial Chemotherapy (2002) 50, 981-987
© 2002 The British Society for Antimicrobial Chemotherapy
Efficacy of atovaquone combined with clindamycin against murine infection with a cystogenic (Me49) strain of Toxoplasma gondii
-Djakovi*
Toxoplasmosis Research Laboratory, Institute for Medical Research, PO Box 102, 11129 Belgrade, Yugoslavia
Received 21 January 2002; returned 13 May 2002; revised 21 June 2002; accepted 16 September 2002
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 
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.
* Corresponding author. Tel: +381-11-685788; Fax: +381-11-643691; E-mail: olgicadj{at}imi.bg.ac.yu
Present address. Institute for Human Genetics, Am Hubland, Biozentrum, 97074 Wurzburg, Germany.
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