![]() The in vitro assessment of susceptibility of Leishmania to antimonial drugs has yielded inconsistent correlations with clinical response to treatment. The immune status of the host, pharmacological factors, and drug lot and manufacturer, as well as the drug susceptibility and biology of different Leishmania species, individually and collectively influence the outcome of treatment, confounding attempts to correlate clinical outcome with susceptibility of parasites in vitro to the drug The multifactorial basis of therapeutic response has obscured the relationship between drug susceptibility and clinical response. The contribution of standard therapy with antimonial drugs to the selection of drug-resistant Leishmania is unknown, as is the role of drug resistance in treatment failure. Numerous clinical trials and case series have shown that a proportion of apparently immunocompetent patients do not respond to antimonial drugs, and, recently, treatment failure has been documented in localized American cutaneous leishmaniasis Diffuse and chronic mucosal leishmaniasis, which are hypo- and hyperresponsive presentations of dermal leishmaniasis, respectively, likewise have poor therapeutic response to antimonials. Relapse after antimonial therapy also occurs in coinfections with Leishmania parasites and HIV, even though the introduction of highly active antiretroviral therapy may delay reactivation. Anthroponotic visceral leishmaniasis in the Bihar state of India responds poorly to antimonial therapy, which fails in 34%–65% of cases. Pentavalent antimonials sodium stibogluconate (Pentostam GlaxoSmithKline) and meglumine antimoniate (Glucantime Aventis) remain the first-line treatment for all clinical forms of leishmaniasis, despite the variable therapeutic response and the growing concern of treatment failure. Selection for resistance to antimony occurs during standard treatment with antimonial drugs, and primary resistance to antimony supports the plausibility of anthroponotic transmission Secondary resistance was documented in 4 patientsĬonclusionsPrimary and secondary resistance to antimony can contribute to treatment failure in American cutaneous leishmaniasis. ![]() At treatment failure, 40% of strains (8/20) were resistant. ResultsBefore treatment, 16% of strains (3/19) showed primary resistance (ED 50 of >128 μg Sb/mL), whereas 84% (16/19) were susceptible (ED 50 of 128 μg Sb/mL. The 50% effective dose (ED 50) of antimony in the form of additive-free meglumine antimoniate was determined for intracellular amastigotes in human promonocytic U-937 cells MethodsWe evaluated the susceptibility to antimony of 19 strains isolated before treatment with meglumine antimoniate and 21 strains isolated at treatment failure from 20 patients. In this study, we sought to determine whether standard treatment selects for resistant organisms and whether drug resistance contributes to treatment failure The role of drug resistance in treatment failure has been difficult to ascertain because therapeutic response is multifactorial, and the efficacy of antimonial drugs depends on an effective immune response. BackgroundFailure of antimonial therapy has been increasingly reported in anthroponotic visceral leishmaniasis and in cutaneous disease.
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