In vitro and in vivo activities of rifampin, streptomycin, amikacin, moxifloxacin, R207910, linezolid, and PA-824 against Mycobacterium ulcerans.
Seven antimicrobials were tested in vitro against 29 clinical isolates of Mycobacterium ulcerans. R207910 demonstrated the lowest MIC(50) and MIC(90), followed by moxifloxacin (MXF), streptomycin (STR), rifampin (RIF), amikacin (AMK), linezolid (LZD), and PA-824. All but PA-824 demonstrated an MIC(90) significantly less than the clinically achievable peak serum level. Administered as monotherapy to mice, RIF, STR, AMK, MXF, R207910, and LZD demonstrated some degree of bactericidal activity, whereas PA-824 failed to prevent mortality and to reduce the mean number of CFU in the footpads. Because 4 or 8 weeks of treatment by the combinations RIF-MXF, RIF-R207910, and RIF-LZD displayed bactericidal effects similar to those of RIF-STR and RIF-AMK, these three combinations might be considered as orally administered combined regimens for treatment of Buruli ulcer. Taking into account the cost, potential toxicity, and availability, the combination RIF-MXF appears more feasible for application in the field; additional experiments with mice are warranted to define further its activity against M. ulcerans. In addition, a pilot clinical trial is proposed to test the efficacy of RIF-MXF for treatment of Buruli ulcer.
Ji
Baohong
B
Bactériologie-Hygiène, Faculté de Médecine Pierre et Marie Curie, Université Paris 6, France. baohong_ji@yahoo.com
Lefrançois
Sébastien
S
Robert
Jerome
J
Chauffour
Aurélie
A
Truffot
Chantal
C
Jarlier
Vincent
V
D000081:Acetamides / Q000008:administration & dosage / Q000627:therapeutic use; D000583:Amikacin / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D001372:Aza Compounds / Q000008:administration & dosage / Q000627:therapeutic use; D015169:Colony Count, Microbial; D064687:Diarylquinolines; D004305:Dose-Response Relationship, Drug; D005260:Female; D024841:Fluoroquinolones; D005528:Foot / Q000382:microbiology; D066298:In Vitro Techniques; D000069349:Linezolid; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D000077266:Moxifloxacin; D009165:Mycobacterium Infections, Nontuberculous / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D019911:Mycobacterium ulcerans / Q000187:drug effects* / Q000254:growth & development; D009593:Nitroimidazoles / Q000008:administration & dosage / Q000627:therapeutic use; D023303:Oxazolidinones / Q000008:administration & dosage / Q000627:therapeutic use; D011804:Quinolines / Q000008:administration & dosage / Q000627:therapeutic use; D012293:Rifampin / Q000008:administration & dosage / Q000627:therapeutic use; D013307:Streptomycin / Q000008:administration & dosage / Q000627:therapeutic use; D016019:Survival Analysis; D013997:Time Factors
D000081:Acetamides; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D001372:Aza Compounds; D064687:Diarylquinolines; D024841:Fluoroquinolones; D009593:Nitroimidazoles; D023303:Oxazolidinones; D011804:Quinolines; C410767:pretomanid; C493870:bedaquiline; D000583:Amikacin; D000069349:Linezolid; D000077266:Moxifloxacin; D012293:Rifampin; D013307:Streptomycin