Failure of both azithromycin and antimony to treat cutaneous leishmaniasis in Manaus, AM, Brazil

Abstract

SUMMARYA non-randomized controlled clinical trial was carried out in order to evaluate both azithromycin and antimony efficacy in cutaneous leishmaniasis in Manaus, AM, Brazil. Forty nine patients from both genders, aged 14 to 70, with cutaneous ulcers for less than three months and a positive imprint for Leishmania spp. amastigotes were recruited into two groups. Group I (26 patients) received a daily-single oral dose of 500 mg of azithromycin for 20 days and Group II (23 patients) received a daily-single intramuscular dose of 20 mg/kg of meglumine antimony, also for 20 days. Azithromycin cured three of 24 (12.5%) patients on days 60, 90 and 120 respectively whereas therapeutic failure was considered in 21 of 24 (87.5%) cases. In group II, antimony cured eight of 19 (42.1%) cases as follows: three on day 30, one each on day 60 and day 90, and three on day 120. Therapeutic failure occurred in 11 of 19 (57.9%) individuals. The efficacy of antimony for leishmaniasis was better than azithromycin but analysis for the intention-to-treat response rate did not show statistical difference between them. Although azithromycin was better tolerated, it showed a very low efficacy to treat cutaneous leishmaniasis in Manaus.

Montenegro Skin Test and Age of Skin Lesion as Predictors of Treatment Failure in Cutaneous Leishmaniasis

“…The percentage of therapeutic failure (14%) was lower than reported in previous studies with meglumine antimoniate treatment (46% to 75%) 12,27,29,33 . Low failure rates found in this study support the effectiveness of low-dose treatment (5 mg Sb 5+ /kg/day) previously reported in studies at INI/FIOCRUZ 19,29 .…”

Genotypic profiles of Leishmania (Viannia) braziliensis strains from cutaneous leishmaniasis patients and their relationship with the response to meglumine antimoniate treatment: a pilot study

“…The efficacy of this regimen in regions where Leishmania (Viannia) braziliensis infections predominate varies between 51.1% and 90%. In Brazil, therapeutic failure defined as a lack of clinical cure after receiving two regular therapeutic courses varies from 46 to 75% [ 2 , 4 , 5 ]. However, antimony resistance is not a national public health concern, and from 50 to 100% of re-treated patients have a favorable outcome [ 2 ].…”

Poor response to azithromycin in cutaneous leishmaniasis leading to a premature interruption of a multicentric phase III clinical trial in Brazil

“…Until now, few studies have tested azithromycin as an alternative treatment for CL [10][11][12]14,15 . Only one study was a randomized clinical trial that compared oral azithromycin and meglumine antimoniate for the treatment of CL in Americas, which included 23 patients in each study group.…”

“…Prata et al 13 showed a cure rate of 85% in an open non-controlled trial with 20 patients 13 . Four studies in Brazil showed low effi cacy of azithromycin when compared with meglumine antimoniate 10,14,15 . Two others studies evaluated azithromycin against Old World leishmaniasis, both with poor responses 11,12 .…”

“…Other treatment options include pentamidine and amphotericin B, which are both injectable and have a safety profi le that is similar to antimony and the lipid formulations of amphotericin B, wich are expensive optionsfor the majority of the CL endemic countries. Various studies evaluated oral drugs as candidates for CL treatment, such as miltefosine [5][6][7] , fl uconazole 8,9 , and azithromycin [10][11][12][13][14][15] , with controversial results or no clear evidence of efficacy.…”