title: In vitro sensitivity of paired Leishmania (Viannia) braziliensis samples isolated before meglumine antimoniate treatment and after treatment failure or reactivation of cutaneous leishmaniasis.
abstract: This study evaluated the in vitro sensitivity of paired Leishmania braziliensis samples isolated from the same patient before pentavalent antimonial treatment (Sample A) and after treatment failure or cutaneous leishmaniasis reactivation (Sample B) in patients undergoing intralesional administration or injections (5 mgSb(V)/kg/d) of meglumine antimoniate. Fourteen samples from 7 patients were studied. After 24 h of drug exposure, 50% lethal dose (LD50) values for promastigotes ranged from 0.37 mg/mL to 5.86 mg/mL for samples obtained before treatment (A) and 0.89 mg/mL to 7.80 mg/mL for samples obtained after treatment (B). After 48 h, LD50 values ranged from 0.37 mg/mL to 5.75 mg/mL and 0.70 mg/mL to 7.68 mg/mL for A and B samples, respectively. After 48 h, LD50 values for amastigotes ranged from 11.7 to 44.3 μg/mL for A samples and 13.7 to 52.7 μg/mL for B samples. Of 7 patients, 1 discontinued treatment and 6 were cured after retreatment with amphotericin B (4 cases) or meglumine antimoniate (2 cases). Overall the B samples had higher LD50 values than A samples; however the difference was not significant. These results do not support the hypothesis that low-dose and intralesional treatments induce selection of resistant parasites in vitro and suggest that other factors may influence therapeutic outcome in patients with poor response to initial treatment.
authors: Núcleo de Biossegurança, Bio-Manguinhos, Fundação Oswaldo Cruz, 21040-900 Rio de Janeiro, RJ, Brazil.
authors: Cibele
authors: C
authors: Baptista
authors: Laboratório de Pesquisa Clínica e Vigilância em Leishmanioses, Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, 21040-900 Rio de Janeiro, RJ, Brazil.
authors: Luciana de Freitas Campos
authors: Lde F
authors: Miranda
authors: Laboratório de Pesquisa Clínica e Vigilância em Leishmanioses, Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, 21040-900 Rio de Janeiro, RJ, Brazil.
authors: Maria de Fátima
authors: Mde F
authors: Madeira
authors: Laboratório de Bioquímica de Tripanosomatídeos, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, 21040-360 Rio de Janeiro, RJ, Brazil.
authors: Leonor Laura Pinto
authors: LL
authors: Leon
authors: Laboratório de Imunoparasitologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, 21040-360 Rio de Janeiro, RJ, Brazil.
authors: Fátima
authors: F
authors: Conceição-Silva
authors: Laboratório de Pesquisa Clínica e Vigilância em Leishmanioses, Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, 21040-900 Rio de Janeiro, RJ, Brazil.
authors: Armando de Oliveira
authors: Ade O
authors: Schubach
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000981:Antiprotozoal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007892:Leishmania braziliensis / Q000187:drug effects* / Q000302:isolation & purification; D007896:Leishmaniasis / Q000188:drug therapy* / Q000469:parasitology; D007928:Lethal Dose 50; D008297:Male; D008536:Meglumine / Q000494:pharmacology* / Q000627:therapeutic use; D000077485:Meglumine Antimoniate; D008875:Middle Aged; D009942:Organometallic Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D012867:Skin / Q000469:parasitology
chemical_list: D000981:Antiprotozoal Agents; D009942:Organometallic Compounds; D008536:Meglumine; D000077485:Meglumine Antimoniate