BENTOUCHA A, ROBERT J, DEGA H, LOUNIS N, JARLIER V, GROSSET J; Interscience Conference on Antimicrobial Agents and Chemotherapy (41st : 2001 : Chicago, Ill.).

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2001 Dec 16-19; 41: abstract no. B-1376.

Bacteriologie, Pitie-Salpetriere, Paris, France

Background. Mycobacterium ulcerans is responsible for Buruli ulcer (BU), the third most prevalent mycobacterial disease throughout the world. To date, no antimicrobial regimen has proven its efficacy, and BU treatment relies on surgical excision followed by skin grafting. Methods. Mice infected in the left hind footpad with 5 log[10] AFB of M. ulcerans were divided into an untreated control group and 17 treatment groups that received one of the following regimens for four weeks: 100 mg/kg of azithromycin (AZM), 100 mg/kg of clarythromycin (CLR) or 50 mg/kg of AZM for a duration of five days a week (daily), or three times a week or once weekly; 100 mg/kg of telithromycin (TLM), sparfloxacin (SPX), or moxifloxacin (MOX); 200mg/kg of levofloxacin (LVX); 100 mg/kg of streptomycin (STR) or amikacin (AMK); 10 mg/kg of rifampin (RIF); and the combination 10 mg/kg of RIF and 100 mg/kg of AMK. All the latter regimens were administered daily. The treatment activity was assessed in term of delay in median time to footpad swelling in treated mice by comparison with untreated mice. Results. Clear-cut bactericidal activity, i.e. a delay longer than the treatment duration, was observed in the STR-, AMK-, and RIF+AMK-treated mice. However, all mice treated with AMK alone or STR had swollen footpads before the end of the observation period, suggesting regrowth of M. ulcerans. On the opposite, 50% of the mice treated with the RIF+AMK combination had no lesion after 30 weeks, suggesting cure. The other regimens displayed either no activity (50 mg/kg AZM, 100 mg/kg AZM thrice weekly, TLM, LVX), bacteriostatic activity, i.e. a delay shorter than the treatment duration (100 mg/kg AZM daily or once weekly, CLR thrice or once weekly, MOX ) or a weak bactericidal activity (CLR daily, SPX). Conclusion. The RIF+AMK and potentially RIF+SM combinations warrant further study in human for the treatment of BU.

Publication Types:

• Meeting Abstracts

Keywords:

• Amikacin
• Animals
• Anti-Bacterial Agents
• Anti-Infective Agents
• Dermatitis
• Fluoroquinolones
• Humans
• Ketolides
• Macrolides
• Mice
• Muridae
• Mycobacterium Infections
• Mycobacterium Infections, Atypical
• Mycobacterium ulcerans
• Ofloxacin
• Rifampin
• Skin Diseases, Bacterial
• Streptomycin
• sparfloxacin
• telithromycin

Other ID:

• GWAIDS0029894

UI: 102269526

From Meeting Abstracts