Cutaneous leishmaniasis (CL) is an endemic parasitic disease of major health impact in many parts of the world and is caused by several species of the protozoan parasite Leishmania. Antimonial compounds (i.e glucantime and pentostam) are the first-line treatment for cutaneous leishmaniasis with emerging drug resistance as a problem. The control of Leishmania is further complicated by the emergence of drug-resistant parasites. In the clinical settings, resistance to SbV containing drugs is now well established and it was found to occur in South America, Europe, the Middle East and most notably in India. Clinical resistance to organic pentavalent antimonials, in the form of sodium stibogluconate (pentostam) or N-methylglucamine antimoniate (glucantime), has long been recognized. However, it is unknown whether the clinical failure of chemotherapy is attributable to the development of drug resistance mechanisms in the parasite or to a variety of host factors that might also contribute to low drug response. Reported rate of drug-resistance to antimonial compounds in Iran varies from 9.4% to 94.2% and there is not any comprehensive study on this issue. Indeed, in the endemic region treatment with SbV fails in more cases; thus, in general patients infected with resistant parasites are unresponsive although exceptions have been reported. This article aims to review the mechanisms of drug resistance to these compounds. The main resistance factors include genetical, enzymatic, intracellular (such as apoptosis and cytoskeleton changes) and resistance proteins. Also, mechanisms related to drug transport and intracellular activation are discussed. Various methods of drug resistance detection such as culture and molecular methods (i.e polymerase chain reaction) are reviewed. Although the exact mechanism of action glucantime is not clear, it seems that protein and gene factors involved in cellular drug entry are the main causes of drug resistance. Cross-sectional studies on meglumine antimoniate resistance in endemic areas of cutaneous leishmaniasis in Iran are highly recommended. Also, studies for evaluation of alternatives therapies for antimonial resistant cases are required.
