A combination of benznidazole and ketoconazole enhances efficacy of chemotherapy of experimental Chagas' disease

Despite the large number of patients infected with Trypanosoma cruzi, there are no commercial drugs available with high efficacy for use in the clinic al treatment of Chagas' disease (American trypanosomiasis). As the prospect s of the introduction of new compounds by the pharmaceutical industry are p oor, alternative strategies are being designed to identify candidates among drugs already available on the market that could be used in combination to provide a synergic effect and improve the efficacy of chemotherapy. In thi s paper we investigated a possible synergic effect of drugs in mice inocula ted with isolates of T. cruzi susceptible (CL), moderately resistant (Y) an d naturally resistant (Colombiana) to benznidazole and nifurtimox. Our data demonstrated that the combination of benznidazole with ketoconazole induce d a synergic effect In mice Infected with the CL and Y isolate of T. cruzi. No differences were observed, however, in animals infected with the Colomb iana isolate, suggesting that the synergic effect of benznidazole and ketoc onazole is influenced by the isolate of parasite and that this could be imp ortant in further studies searching for useful combinations of drugs. Moreo ver, we observed that early treatment with ketoconazole could increase the cure rate in animals infected with the Y isolate. No positive effect, in re lation to cure rate, was observed with the combination of benznidazole and ofloxacin. Our results re-emphasize the importance of identifying those com pounds already on the market with synergic effects able to enhance the cure of T. cruzi Infection.