In vitro interactions between sitamaquine and amphotericin B, sodium stibogluconate, miltefosine, paromomycin and pentamidine against Leishmania donovani.


Seifert, K; Munday, J; Syeda, T; Croft, SL; (2011) In vitro interactions between sitamaquine and amphotericin B, sodium stibogluconate, miltefosine, paromomycin and pentamidine against Leishmania donovani. The Journal of antimicrobial chemotherapy, 66 (4). pp. 850-4. ISSN 0305-7453 DOI: 10.1093/jac/dkq542

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Abstract

OBJECTIVES: To evaluate in vitro interactions between sitamaquine and the current antileishmanial drugs amphotericin B, sodium stibogluconate, miltefosine, paromomycin and pentamidine against intracellular Leishmania donovani amastigotes in peritoneal mouse macrophages. A second objective was to evaluate the susceptibility of antimony-resistant L. donovani isolates to sitamaquine.<br/> METHODS: Mouse peritoneal macrophages were infected with L. donovani amastigotes. Drug susceptibility was assessed in a standard 5 day assay and drug interactions with a modified fixed ratio isobologram method. Fractional inhibitory concentrations (FICs), sum FICs (∑FICs) and an overall mean ∑FIC were calculated for each combination. The nature of interaction was classified on the basis of the mean ∑FIC as follows: synergy as mean ∑FIC≤0.5, indifference as mean ∑FIC between >0.5 and ≤4 and antagonism as mean ∑FIC>4.<br/> RESULTS: Interactions between sitamaquine and amphotericin B, sodium stibogluconate, paromomycin and miltefosine were classified as indifferent at the 50% and 90% effective concentration (EC50 and EC90, respectively) levels. The sitamaquine/pentamidine combination was synergistic, with overall mean ∑FICs from 0.5 to 0.6 at the EC50 level and from 0.3 to 0.7 at the EC90 level. Sitamaquine displayed in vitro activity against L. donovani isolates resistant to sodium stibogluconate.<br/> CONCLUSIONS: This study expands the preclinical data on drug combinations and provides the basis for further studies as antileishmanial chemotherapy is moving towards multidrug treatment regimens.<br/>

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Research Centre: Antimicrobial Resistance Centre (AMR)
Leishmaniasis Group
PubMed ID: 21393188
Web of Science ID: 288551300025
URI: http://researchonline.lshtm.ac.uk/id/eprint/1205

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