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

Abstract

Abstract. Anti-leishmaniasis drug resistance is a common problem worldwide. The aim of this study was to inventory the general in vitro level of sensitivity of Leishmania isolates circulating in French Guiana and to highlight potential in vitro pentamidine-resistant isolates. This sensitivity study was conducted on 36 patient-promastigote isolates for seven drugs (amphotericin B, azithromycin, fluconazole, meglumine antimoniate, miltefosine, paromomycin, and pentamidine) using the Cell Counting Kit-8 viability test. The IC 50 values obtained were heterogeneous. One isolate exhibited high IC 50 values for almost all drugs tested. Pentamidine, which is the first-line treatment in French Guiana, showed efficacy at very low doses (mean of 0.0038 μg/mL). The concordance of the in vitro pentamidine results with the patients' clinical outcomes was 94% (K = 0.82).

Intraspecies differences in natural susceptibility to amphotericine B of clinical isolates of Leishmania subgenus Viannia

“…(V . ) braziliensis present a range of susceptibility that is much wider than previous reports [ 24 , 46 , 47 ]. The reverse was found for L .…”

“…(V . ) braziliensis isolates from French Guiana [ 24 ]. The authors reported EC 50 values with wide variability, ranging between 1.03 and >25 μg/ml AmB for L .…”

“…The variation in EC 50 results between studies could be associated with the experimental conditions of each study, such as the parasite concentration, growth phase used and drug concentration [ 48 ]. Other variables to consider are the time of exposure to the drug [ 49 , 50 ], the culture medium used [ 24 , 51 ], the formulation and the method used to assess the effect of the medication [ 35 ]. Differences in these variables between experiments make comparisons of the results difficult.…”

“…guyanensis . This pattern could be partially explained by the differences in the numbers of isolates in the two studies and the prevalence of this species in Colombia and French Guiana [ 24 ]. No reports were found for clinical isolates of L .…”

Of Drugs and Trypanosomatids: New Tools and Knowledge to Reduce Bottlenecks in Drug Discovery

“…Moreover, this determination could be biased by many confounding factors that can reduce lab-to-lab reproducibility and lead to false hit discoveries. These factors could include macrophage infection rate, incomplete amastigogenesis, impact of distinct culture media, as well as the intrinsic pathogenicity of the strain selected for the assay [ 39 , 40 , 41 ].…”