title: Sterilizing Activity of Fully Oral Intermittent Regimens against Mycobacterium Ulcerans Infection in Mice.
abstract: 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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, CR7, INSERM, U1135, Centre d'Immunologie et des Maladies Infectieuses, CIMI, Team E13 (Bactériologie), F-75013, Paris, France.
authors.forename: Aurélie
authors.identifier: http://orcid.org/0000-0002-8846-5069
authors.initials: A
authors.lastname: Chauffour
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, CR7, INSERM, U1135, Centre d'Immunologie et des Maladies Infectieuses, CIMI, Team E13 (Bactériologie), F-75013, Paris, France.|APHP, Centre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux (CNR-MyRMA), Bactériologie-Hygiène, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix, F-75013, Paris, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Robert
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, CR7, INSERM, U1135, Centre d'Immunologie et des Maladies Infectieuses, CIMI, Team E13 (Bactériologie), F-75013, Paris, France.|APHP, Centre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux (CNR-MyRMA), Bactériologie-Hygiène, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix, F-75013, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Veziris
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, CR7, INSERM, U1135, Centre d'Immunologie et des Maladies Infectieuses, CIMI, Team E13 (Bactériologie), F-75013, Paris, France.|APHP, Centre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux (CNR-MyRMA), Bactériologie-Hygiène, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix, F-75013, Paris, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Aubry
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, CR7, INSERM, U1135, Centre d'Immunologie et des Maladies Infectieuses, CIMI, Team E13 (Bactériologie), F-75013, Paris, France.|APHP, Centre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux (CNR-MyRMA), Bactériologie-Hygiène, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix, F-75013, Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Jarlier
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D054312:Buruli Ulcer / Q000188:drug therapy* / Q000382:microbiology; D017291:Clarithromycin / Q000008:administration & dosage; D064687:Diarylquinolines / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D005260:Female; D024841:Fluoroquinolones / Q000008:administration & dosage; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D000077266:Moxifloxacin; D019911:Mycobacterium ulcerans / Q000187:drug effects / Q000502:physiology; D012293:Rifampin / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D000900:Anti-Bacterial Agents; D064687:Diarylquinolines; D024841:Fluoroquinolones; C493870:bedaquiline; D017291:Clarithromycin; D000077266:Moxifloxacin; D012293:Rifampin; C018421:rifapentine