title: In vitro interaction between paromomycin sulphate and four drugs with leishmanicidal activity against three New World Leishmania species.
abstract: OBJECTIVE
  To evaluate in vitro interactions between paromomycin sulphate and the antileishmanial drugs meglumine antimoniate, amphotericin B, miltefosine and azithromycin against intracellular Leishmania (Leishmania) infantum chagasi, Leishmania (Viannia) braziliensis and Leishmania (Leishmania) amazonensis amastigotes in peritoneal mouse macrophages.
  
  
  METHODS
  First, drug susceptibility was assessed in 3, 5 and 7 day assays, followed by drug interaction assays with a modified fixed-ratio method. An overall mean sum fractional inhibitory concentration (∑FIC) was calculated for each combination and each Leishmania species. The nature of the interactions was classified as synergistic if the mean ∑FIC was ≤ 0.5, indifferent if the mean ∑FIC was >0.5-4.0 and antagonistic if the mean ∑FIC was >4.0.
  
  
  RESULTS
  In vitro synergism was observed for the combinations of paromomycin plus miltefosine [at 50% and 90% inhibitory concentrations (IC50 and IC90, respectively)] and paromomycin plus amphotericin B (at the IC90 level) against L. (L.) amazonensis, paromomycin plus meglumine antimoniate (at the IC50 and IC90 levels) and paromomycin plus amphotericin B (at the IC50 level) against L. (V.) braziliensis, and paromomycin plus miltefosine, paromomycin plus amphotericin B (both at the IC90 level) and paromomycin plus azithromycin (at the IC50 level) against L. (L) infantum chagasi.
  
  
  CONCLUSIONS
  This work provides a preclinical dataset that supports future studies on multidrug treatment schedules against New World leishmaniasis.
authors: Laboratório de Pesquisas Clínicas - Centro de Pesquisas René Rachou-Fundação Oswaldo Cruz - FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil.
authors: Eliane
authors: E
authors: de Morais-Teixeira
authors: Mariana Kolos
authors: MK
authors: Gallupo
authors: Lucas Fonseca
authors: LF
authors: Rodrigues
authors: Alvaro José
authors: AJ
authors: Romanha
authors: Ana
authors: A
authors: Rabello
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D004357:Drug Synergism; D020128:Inhibitory Concentration 50; D007892:Leishmania braziliensis / Q000187:drug effects*; D018314:Leishmania infantum / Q000187:drug effects*; D007894:Leishmania mexicana / Q000187:drug effects*; D008264:Macrophages / Q000469:parasitology; D051379:Mice; D021261:Parasitic Sensitivity Tests; D010303:Paromomycin / Q000494:pharmacology*
chemical_list: D000981:Antiprotozoal Agents; D010303:Paromomycin
keywords: drug combinations; drug susceptibility tests; leishmaniasis; treatments