In-vitro activity of avermectins against Mycobacterium ulcerans
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In-vitro activity of avermectins against Mycobacterium ulcerans. / Omansen, Till F.; Porter, Jessica L; Johnson, Paul D R; van der Werf, Tjip S; Stienstra, Ymkje; Stinear, Timothy P.
in: PLOS NEGLECT TROP D, Jahrgang 9, Nr. 3, 03.2015, S. e0003549.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - In-vitro activity of avermectins against Mycobacterium ulcerans
AU - Omansen, Till F.
AU - Porter, Jessica L
AU - Johnson, Paul D R
AU - van der Werf, Tjip S
AU - Stienstra, Ymkje
AU - Stinear, Timothy P
PY - 2015/3
Y1 - 2015/3
N2 - 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.
AB - 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.
KW - Administration, Oral
KW - Buruli Ulcer/drug therapy
KW - Ivermectin/analogs & derivatives
KW - Microbial Sensitivity Tests
KW - Mycobacterium ulcerans/drug effects
KW - Rifampin/administration & dosage
KW - Streptomycin/administration & dosage
U2 - 10.1371/journal.pntd.0003549
DO - 10.1371/journal.pntd.0003549
M3 - SCORING: Journal article
C2 - 25742173
VL - 9
SP - e0003549
JO - PLOS NEGLECT TROP D
JF - PLOS NEGLECT TROP D
SN - 1935-2735
IS - 3
ER -