In-vitro activity of avermectins against Mycobacterium ulcerans.
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.
Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia; University of Groningen, University Medical Center Groningen, Department of Internal Medicine/Infectious Diseases, Groningen, The Netherlands.
Till F
TF
Omansen
Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia.
Jessica L
JL
Porter
Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia; Austin Centre for Infection Research (ACIR), Infectious Diseases Department, Austin Health, Heidelberg, Victoria, Australia; Department of Medicine, University of Melbourne, Heidelberg, Victoria, Australia.
Paul D R
PD
Johnson
University of Groningen, University Medical Center Groningen, Department of Internal Medicine/Infectious Diseases, Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, Department of Pulmonary Diseases and Tuberculosis, Groningen, The Netherlands.
Tjip S
TS
van der Werf
University of Groningen, University Medical Center Groningen, Department of Internal Medicine/Infectious Diseases, Groningen, The Netherlands.
Ymkje
Y
Stienstra
Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia.
Timothy P
TP
Stinear
D000284:Administration, Oral; D054312:Buruli Ulcer / Q000188:drug therapy; D007559:Ivermectin / Q000031:analogs & derivatives* / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D019911:Mycobacterium ulcerans / Q000187:drug effects* / Q000254:growth & development; D012293:Rifampin / Q000008:administration & dosage; D013307:Streptomycin / Q000008:administration & dosage
D007559:Ivermectin; C019264:avermectin; D012293:Rifampin; D013307:Streptomycin