Sterilizing Activity of Fully Oral Intermittent Regimens against Mycobacterium Ulcerans Infection in Mice

Background: the treatment of buruli ulcer (bu) that is caused by mycobacterium ulcerans,is currently based on a daily administration of rifampin and streptomycin (rif-str). a fully oral intermittent regimen would greatly simplify its treatment on the field. methodology/principal findings: the objective of this study was to assess the bactericidal and sterilizing activities of intermittent oral regimens in a murine model of established m. ulcerans infection. regimens combining rifapentine (rfp 20 mg/kg) with either moxifloxacin (mxf 200 mg/kg),clarithromycin (clr 100 mg/kg) or bedaquiline (bdq 25 mg/kg) were administrated twice (2/7) or three (only for rfp-clr 3/7) times weekly during 8 weeks. the bactericidal but also the sterilizing activities of these four intermittent oral regimens were at least as good as those obtained with control weekdays regimens,i.e. rfp-clr 5/7 or rif-str 5/7. a single mouse from the rfp-mfx 2/7 group had culture-positive relapse at the end of the 28 weeks following treatment completion among the 157 mice treated with one of the four intermittent regimens (40 rfp-clr 2/7,39 rfp-clr 3/7,39 rfp-mxf 2/7,39 rfp-bdq 2/7). conclusions/significance: these results open the door for a fully intermittent oral drug regimen for bu treatment avoiding intramuscular injections and facilitating supervision by health care workers. © 2016 chauffour et al.