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Antimicrobial Agents and Chemotherapy, June 2006, p. 1921-1926, Vol. 50, No. 6
0066-4804/06/$08.00+0     doi:10.1128/AAC.00052-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

In Vitro and In Vivo Activities of Rifampin, Streptomycin, Amikacin, Moxifloxacin, R207910, Linezolid, and PA-824 against Mycobacterium ulcerans

Baohong Ji,* Sébastien Lefrançois, Jerome Robert, Aurélie Chauffour, Chantal Truffot, and Vincent Jarlier

Bactériologie-Hygiène, Faculté de Médecine Pierre et Marie Curie, Université Paris 6, Paris, France

Received 12 January 2006/ Returned for modification 9 February 2006/ Accepted 22 March 2006

Seven antimicrobials were tested in vitro against 29 clinical isolates of Mycobacterium ulcerans. R207910 demonstrated the lowest MIC50 and MIC90, followed by moxifloxacin (MXF), streptomycin (STR), rifampin (RIF), amikacin (AMK), linezolid (LZD), and PA-824. All but PA-824 demonstrated an MIC90 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.

* Corresponding author. Mailing address: Bactériologie-Hygiène, Faculté de Médecine Pierre et Marie Curie, Université Paris 6, 91 boulevard de l'Hôpital, 75634 Paris Cedex 13, France. Phone: (331) 40 77 98 67. Fax: (331) 45 82 75 77. E-mail: baohong_ji{at}yahoo.com.

Antimicrobial Agents and Chemotherapy, June 2006, p. 1921-1926, Vol. 50, No. 6
0066-4804/06/$08.00+0     doi:10.1128/AAC.00052-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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