Selamectin Is the Avermectin with the Best Potential for Buruli Ulcer Treatment.
A comprehensive analysis was done to evaluate the potential use of anti-parasitic macrocyclic lactones (including avermectins and milbemycins) for Buruli ulcer (BU) therapy. A panel containing nearly all macrocyclic lactones used in human or in veterinary medicine was analyzed for activity in vitro against clinical isolates of Mycobacterium ulcerans. Milbemycin oxime and selamectin were the most active drugs against M. ulcerans with MIC values from 2 to 8 μg/mL and 2 to 4 μg/mL, respectively. In contrast, ivermectin and moxidectin, which are both in clinical use, showed no significant activity (MIC> 32 μg/mL). Time-kill kinetic assays showed bactericidal activity of selamectin and in vitro pharmacodynamic studies demonstrated exposure-dependent activity. These data together with analyses of published pharmacokinetic information strongly suggest that selamectin is the most promising macrocyclic lactone for BU treatment.
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland.
Nicole
N
Scherr
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland.
Gerd
G
Pluschke
Department of Microbiology and Immunology, Centre for Tuberculosis Research, Life Sciences Centre, University of British Columbia, Vancouver, British Columbia, Canada.
Charles J
CJ
Thompson
Department of Microbiology and Immunology, Centre for Tuberculosis Research, Life Sciences Centre, University of British Columbia, Vancouver, British Columbia, Canada.
Santiago
S
Ramón-García
D000977:Antiparasitic Agents / Q000627:therapeutic use*; D054312:Buruli Ulcer / Q000188:drug therapy* / Q000382:microbiology*; D006801:Humans; D007559:Ivermectin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008826:Microbial Sensitivity Tests; D019911:Mycobacterium ulcerans / Q000187:drug effects*
D000977:Antiparasitic Agents; D007559:Ivermectin; C414354:selamectin