Evaluation of the activity of the combination of azithromycin plus fluconazole against Leishmania (V) braziliensis and Leishmania (L) amazonensis in golden hamsters

FRAGUEIRO FRÍAS, V; LUNA, C; TOMÁS, G; NEGRI, V; RIARTE, A; ABRAHAM, D; KROLEWIECKI, A

Atlanta

Encuentro; 61 Annual Meeting of the American Society of Tropical Medicine and Hygiene; 2012

American Society of Tropical Medicine and Hygiene

The exploration of new oral therapeutic options for the treatment of American Cutaneous Leishmaniasis is a research priority with a potentially significant impact in patient management. We have demonstrated the activity of azithromycin PO against L. braziliensis although inferior to meglumine antimoniate, whereas no activity on L. amazonensis was detected. In the current study, golden hamsters were infected on hind foot with 5x105 metacyclic promastigotes of L. braziliensis or L. amazonensis. Five groups were established: azithromycin PO 400 mg/kg/day (A); fluconazole PO 80 mg/kg/day (F); azithromycin PO plus fluconazole PO 20 mg/kg/day (F/A); meglumine antimoniate IM 60 mg/kg/day (G) and untreated animals (C). The treatment was administered immediately after infection and for 28 days. Size of lesions was determined weekly. A week after finishing treatment, animals were sacrificed. Parasite load in skin was measured by limiting dilution assay and cultures of skin, lymph node and spleen were made. In the L. braziliensis model, there were no significant difference in the progression of size of lesions in G compared to F/A, except in week 5, one week after treatments were completed, when G performed significantly better. Lesion size was smaller in G vs. C from week 2 until the end of the study, and in G vs. A in weeks 4 and 5. Similarly, F/A showed smaller lesion size since week 3 comparing to C. There were no significant differences in paired comparisons of other groups. In the limiting dilution assay, G, F/A and A showed no differences between them, while they showed less parasite burden than F and C. There was no difference between F and C. Cultures of infected foot and lymph node were positive in almost all animals, while the positivity of spleen were 50% in C, 40% in F, 10% in F/A and 0% in G and A. In the L. amazonensis model, only G showed activity. In conclusion, fluconazole alone has no activity for L. braziliensis and the combination fluconazole/azithromycin appears to have no additional effect than azithromycin monotherapy.