In-vitro activity of avermectins against Mycobacterium ulcerans.

PLoS neglected tropical diseases (2015-03-06)
Till F Omansen, Jessica L Porter, Paul D R Johnson, Tjip S van der Werf, Ymkje Stienstra, Timothy P Stinear
ABSTRACT

Mycobacterium ulcerans causes Buruli ulcer (BU), a debilitating infection of subcutaneous tissue. There is a WHO-recommended antibiotic treatment requiring an 8-week course of streptomycin and rifampicin. This regime has revolutionized the treatment of BU but there are problems that include reliance on daily streptomycin injections and side effects such as ototoxicity. Trials of all-oral treatments for BU show promise but additional drug combinations that make BU treatment safer and shorter would be welcome. Following on from reports that avermectins have activity against Mycobacterium tuberculosis, we tested the in-vitro efficacy of ivermectin and moxidectin on M. ulcerans. We observed minimum inhibitory concentrations of 4-8 μg/ml and time-kill assays using wild type and bioluminescent M. ulcerans showed a significant dose-dependent reduction in M. ulcerans viability over 8-weeks. A synergistic killing-effect with rifampicin was also observed. Avermectins are well tolerated, widely available and inexpensive. Based on our in vitro findings we suggest that avermectins should be further evaluated for the treatment of BU.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Rifampicin, ≥97% (HPLC), powder
Sigma-Aldrich
Rifampicin, suitable for plant cell culture, BioReagent, ≥97% (HPLC), crystalline
Supelco
Moxidectin, VETRANAL®, analytical standard
Rifampicin, European Pharmacopoeia (EP) Reference Standard
Moxidectin, European Pharmacopoeia (EP) Reference Standard
Moxidectin for system suitability, European Pharmacopoeia (EP) Reference Standard

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