Azithromycin for the treatment of American Cutaneous Leishmaniasis: Pre-clinical and clinical data

KROLEWIECKI, A; TARANTO, N; SINAGRA, A; CAJAL, SP; LUNA, C; JUAREZ, M; ROMERO, H; MIMORI, T; DI PAOLO, A; TAMAMI, M; RIARTE, R; ABRAHAM, D

Filadelfia, EEUU

Congreso; American Society of Tropical Medicine and Hygiene 56th Annual Meeting; 2007

American Society of Tropical Medicine and Hygiene

Azithromycin was shown to have activity against Leishmania major in vitro and in a mouse model and therefore is a potential oral alternative for the treatment of leishmaniasis. The current animal and human study evaluated the activity of azithromycin against species of Leishmania causing cutaneous disease in Argentina.  Golden hamsters, infected through footpad injections with metacyclic promastigotes of Leishmania (V) braziliensis or Leishmania (L) amazonensis, were treated at the start of infection with azithromycin at doses of 450mg/Kg orally and compared to untreated controls and animals treated with meglumine antimoniate (MA).  Measurement of footpad thickness, lesion cultures and analysis of disease dissemination were performed.  Patients from Northwestern Argentina with confirmed diagnoses of cutaneous leishmaniasis were randomized into groups receiving oral azithromycin 500mg/day (22 patients) or intramuscular MA, 10mgSb/Kg/day (23 patients), both for 28 days and followed for one year. Efficacy was defined as complete re-epithelization without relapse for 12 months after completing therapy. Identification of infecting species from the lesions was done by PCR analysis. Treatment of Golden hamsters with oral azithromycin had no activity against infections with L. (L) amazonensis.  Azithromycin demonstrated significant activity at controlling lesion size caused by L. (V) braziliensis relative to untreated controls but was inferior to meglumine antimoniate,. Neither drug was able to totally eliminate parasites from the lesions in hamsters.  In the clinical trial azithromycin, which was well tolerated, cured 45.5% of the patients whereas  meglumine antimoniate cured 82.6% of the patients,. In 17 patients, species identification was obtained and demonstrated L (V) braziliensis in all cases.  It was concluded from both the animal and the human studies that oral azithromycin had moderate activity  as monotherapy against L (V) braziliensis, with no  activity against L (L) amazonensis.