Combination therapy is now being used for many infectious diseases, such as tuberculosis, malaria, and HIV.

Combination therapy offers the potential of preventing drug resistance, because organisms resistant to one of the drugs may be susceptible to the other drug; and also the potential to diminish drug therapy duration and thus side effects. These two potential benefits to some extent contradict each other: preventing resistance is best done if full courses of both drugs is used; diminishing therapy duration means using less than the full course of each drug. The optimum combination regimen is one in which sufficient amounts of both drugs are used to have high efficacy, yet the amounts are as low as possible to spare patients unnecessarily long courses of drug.

Until recently, the standard treatment for the leishmaniases was pentavalent antimony (Glucantime or Pentostam).

The cure rate for L panamensis in Colombia is 91%-93% [Soto, 1993; Velez, 1997] and the cure rate in Bolivia, in work soon to be completed, is also 90% [ Soto, unpublished results]. A large study with several formulations of antimony found a combined Bolivia-Colombia cure rate of 86% [Soto, 2004b]. Nevertheless, pentavalent antimonials have the disadvantages of multiple injections and mild-moderate clinical toxicity [gastrointestinal complaints, liver enzyme elevations, pancreatic enzyme elevations], all of which are particularly unpleasant for a moderate clinical problem such as cutaneous leishmaniasis. The oral agent Miltefosine has now been shown to be as effective as antimony in Colombia and Bolivia. In Colombia, the cure rate for miltefosine was 91% [Soto 2004a] and in the soon to be completed comparative trial in Bolivia, the cure rate for miltefosine appears to be 92% [Soto, unpublished results]. Side effects seen in patients with cutaneous disease that can be specifically attributed to the drug are nausea and vomiting of mild grade in approximately 25% of patients, and low-grade elevation of creatinine also in approximately 25% of patients [Soto 2001; Soto 2004]. A further disadvantage of miltefosine is that regimens shorter than 4 weeks have not been evaluated for cutaneous disease.