Sensitivity of Leishmania Braziliensis Promastigotes to Meglumine Antimoniate (Glucantime) Is Higher Than That of Other Leishmania Species and Correlates With Response to Therapy in American Tegumentary Leishmaniasis

Abstract

The first line drugs for the treatment of leishmaniasis are antimonial derivatives. Poor clinical response may be credited to factors linked to the host, the drug, or the parasite. We determined the sensitivity of Leishmania sp. promastigotes and amastigotes by counting parasites exposed to increasing concentrations of meglumine antimoniate (Glucantime). Leishmania braziliensis promastigotes were significantly more sensitive than those belonging to other species. The sensitivity of L. braziliensis isolates from patients with unfavorable clinical outcome, such as therapeutic failure or relapse, was significantly lower than those from patients who had clinical cure. Poor clinical response to therapy (therapeutic failure or relapse) was also associated with inadequate antimonial therapy. We also found a significant and positive correlation between promastigotes and intracellular amastigotes with regard to their in vitro susceptibilities to meglumine antimoniate. Our data provide evidence for an association between the sensitivity of promastigotes to antimonials in vitro and clinical response to therapy in American tegumentary leishmaniasis. The high sensitivity of the local L. braziliensis to meglumine antimoniate in vitro provides an explanation for the good clinical response of cutaneous leishmaniasis in the municipality of Rio de Janeiro, Brazil, even when low-dose regimens are employed.

In Vitro Sensitivity of Cutaneous Leishmania Promastigote Isolates Circulating in French Guiana to a Set of Drugs

“…45 Here, we observed a 94% correlation between the in vitro pentamidine results and patient outcomes. Moreover, there is concordance between in vitro promastigotes and intracellular amastigotes 46 for antimonials, when they are in the identical environment. 47 The axenic amastigote form has been suggested to be a possible alternative, because of its morphological and metabolic similarity to the intracellular macrophage amastigote form, 48 but it shares the same drawback with the promastigote form because of its inability to accumulate drugs as macrophages do.…”

American cutaneous leishmaniasis caused by Leishmania (Viannia) braziliensis resistant to meglumine antimoniate, but with good response to pentamidine: a case report

“…In vitro sensitivity testing of the parasites isolated after the two intramuscular treatments and after the six intralesional injections of antimonials revealed differences between the isolates. According to AzeredoCoutinho et al 9 , L. (V.) braziliensis strains presented IC 50 values varying from 0.8 to 9.5mg/mL and the strains isolated from patients poorly responsive to therapy showed significantly higher IC 50 values than those isolated from patients who were cured after completion of the first antimonial treatment 9 . In the present study, the parasites isolated from the first biopsy were more sensitive to antimonials (0.26mg/mL) than those isolated after intralesional treatment (2.10mg/mL), a finding suggesting the development of resistance to the drug after successive cycles of treatment.…”

Risk factors associated with dizziness during treatment of mucosal leishmaniasis with meglumine antimoniate: 16-year retrospective study of cases from Rio de Janeiro, Brazil

“…1,4 The two main therapeutic agents, meglumine antimoniate and sodium stibogluconate, differ in terms of dosage, treatment duration and administration frequency (continuous or intermittent). [5][6][7][8][9] At the Laboratory of Leishmaniasis Surveillance, Evandro Chagas Clinical Research Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil, we have found continuous or intermittent intramuscular administration of meglumine antimoniate at a dose of 5 mg/kg/day to be effective and well tolerated. [10][11][12][13][14][15] The main side effects of treatment with pentavalent antimonials are myalgia, arthralgia, electrocardiographic Q-T interval prolongation, renal failure and pancreatitis accompanied by elevated lipase levels, among others.…”