The activity of azithromycin against Leishmania (Viannia) braziliensis and Leishmania (Leishmania) amazonensis in the golden hamster model

Abstract

New therapeutic alternatives against leishmaniasis remain a priority. The activity of azithromycin against Leishmania (Leishmania) major has been previously demonstrated. Different responses among species of Leishmania make species-specific drug screening necessary. The activity of azithromycin against Leishmania (Viannia) braziliensis and Leishmania (Leishmania) amazonensis was evaluated in golden hamsters infected through footpad injections of metacyclic promastigotes, and compared with untreated controls and animals treated with meglumine antimoniate. Footpad thickness, lesion cultures and dissemination sites were analyzed. Treatment of golden hamsters with oral azithromycin at 450mg/kg had no activity against infections with Leishmania (Leishmania) amazonensis. For infections due to Leishmania (Viannia) braziliensis, azithromycin demonstrated significant activity relative to untreated controls, but inferior to meglumine antimoniate, for controlling lesion size. Neither drug was able to totally eliminate parasites from the lesions. It was concluded that azithromycin has activity against Leishmania (Viannia) braziliensis but not against Leishmania (Leishmania) amazonensis in this model.

Oral azithromycin versus its combination with miltefosine for the treatment of experimental Old World cutaneous leishmaniasis

“…For infections due to L. braziliensis, azithromycin demonstrated significant activity relative to untreated controls, but inferior to meglumine antimoniate, for controlling lesion size. Neither drug was able to totally eliminate parasites from the lesions (Sinagra et al 2007). In addition, the previously reported clinical experiences include an uncontrolled study that involved 20 patients with CL in an area endemic for L. (Viannia) braziliensis treated with variable doses of azithromycin for two to ten days with a cure rate of 85 % (Prata et al 2003).…”

“…Dissemination was also evaluated by tissue culturing in N.N.N. medium for 7 days, after which the presence of live parasites was determined (Sinagra et al 2007). …”

“…Krolewiecki et al (2002) demonstrated that, azithromycin has antileishmanial activity following its subcutaneous adminstration in BALB\c mice infected with Leishmania major. Moreover, Sinagra et al (2007) reported significant activity of its oral adminstration against Leishmania (Viannia) braziliensis however, no activity against infections with Leishmania (Leishmania) amazonensis in golden hamsters could be observed. Recently, azithromycin and a structuraly similar antibiotic clarithromycin showed in vitro activity against promastigotes and amastigotes of L. tropica (Balcioglu et al 2012).…”

A combination DNA vaccine encoding nucleoside hydrolase 36 and glycoproteine 63 protects female but not male hamsters againstLeishmania mexicana

“…Disease development was monitored for up to 17 weeks after infection by weekly measurement of footpad size with a vernier caliper, and lesion size was expressed as the difference in size between the infected and the contralateral uninfected footpad as described before (Saravia et al, 2005). Footpad swelling is indeed well correlated with parasite load during murine infection with L. mexicana (Aguilar Torrentera et al, 2002), as well as in golden hamsters infected with L. brasiliensis or L. amazonensis (Sinagra et al, 2007). It is thus a reliable indicator of disease progression.…”

Topical liposomal azithromycin in the treatment of acute cutaneous leishmaniasis

“…In addition, therapeutic levels of this medication are maintained up to 5 days after the administration of the final dose. Azithromycin is also effective against certain leishmania species both in vitro and in vivo .…”