DHOPLE AM; 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. E-722.

Florida Institute of Technology, Melbourne, FL

BACKGROUND: M. ulcerans infection causes skin ulcers called Buruli ulcer for which there is no effective drug and mainstay of treatment is surgical excision. In order to develop effective chemotherapy, studies were undertaken to evaluate various fluoroquinolones, and rifampin analogs, either singly or in combination with each other, for their activities against this organism. Both type strains and clinical isolates of M. ulcerans were used. METHODS: For in vitro studies BACTEC method was followed to determine MIC and MBC, while mouse footpad model was chosen for in vivo studies. RESULTS: In the in vitro studies, sitafloxacin (DU-6859a) was found to be the most potent fluoroquinolone (MIC, 0.125-0.25 mg/ml), followed by levofloxacin and sparfloxacin (MIC, 0.25 - 1.0 mg/ml) and ciprofloxacin and ofloxacin (MIC, 0.5 - 2.0 mg/ml). Among the rifampin analogs, KRM-1648 exhibited the highest activity (MIC, 0.012 - 0.025 mg/ml), followed by KRM-2312, rifampin and rifabutin. Only sitafloxacin exhibited synergism when combined individually with all three rifampin analogs, while synergism was observed when ofloxacin was combined with KRM -1648, but not with rifampin or rifabutin. In the mouse footpad studies, sitafloxacin, at 25 mg/kg body weight/day, or KRM-1648 or rifabutin, when each fed at 0.001% concentration, totally inhibited the growth of M. ulcerans in the mouse footpads and the action was bactericidal. To achieve bactericidal effects, the concentrations of ofloxacin and rifampin were 100 mg/kg bodyweight/day or 0.008% resp. Again, synergism was observed when sitafloxacin, and not other fluoroquinolones, were combined with KRM-1648, rifampin or rifabutin. Against actively growing organisms in the footpads, the results were the same. CONCLUSIONS: Thus, sitafloxacin and KRM-1648 seem to be the most potent drugs against M. ulcerans, both in vitro as well as in mouse footpad system, and their efficacies should be explored further in treatment of Buruli ulcers.

Publication Types:

• Meeting Abstracts

Keywords:

• Animals
• Ciprofloxacin
• Fluoroquinolones
• In Vitro
• KRM 1648
• Mice
• Microbial Sensitivity Tests
• Mycobacterium Infections, Atypical
• Mycobacterium ulcerans
• Ofloxacin
• Rifabutin
• Rifampin
• Rifamycins
• sitafloxacin
• sparfloxacin

Other ID:

• GWAIDS0029257

UI: 102268889

From Meeting Abstracts