ABSTRACT
The in-vitro antibacterial activity of sitafloxacin (DU-6859a) against Mycobacterium leprae was evaluated and compared with those of ofloxacin, levofloxacin, and ciprofloxacin. Two biochemical indicators (intracellular ATP and uptake of [(3)H]-thymidine) were used to measure the in-vitro growth of M. leprae in Dhople-Hanks (DH) medium. Sitafloxacin was found to be more potent than the other three commonly used fluoroquinolones, with the minimum inhibitory concentration (MIC) against M. leprae being 0.1875 microg/ml and the action being bactericidal. The MICs of ofloxacin, levofloxacin, and ciprofloxacin were 1.5, 0.75, and 3.0 microg/ml, respectively. Similar to ofloxacin and levofloxacin, sitafloxacin also exhibited synergistic activity when combined with either rifabutin or KRM-1648, but not with rifampin. Thus, further studies on the incorporation of sitafloxacin in multidrug therapy regimens in treating leprosy patients are suggested.
Subject(s)
Anti-Infective Agents/pharmacology , Fluoroquinolones , Mycobacterium leprae/drug effects , Animals , Armadillos , Drug Synergism , Drug Therapy, Combination , Humans , Leprostatic Agents/pharmacology , Microbial Sensitivity Tests , Rifabutin/pharmacology , Rifampin/analogs & derivatives , Rifampin/pharmacology , Rifamycins/pharmacologyABSTRACT
The antimicrobial effects of sitafloxacin (DU-6859a) against Mycobacterium leprae, either singly or in combination with either rifampicin, rifabutin or KRM-1648, were studied using a mouse footpad assay technique and the results were compared with those obtained with ofloxacin. When used singly, the minimum concentrations of sitafloxacin and ofloxacin needed to inhibit completely the growth of M. leprae were 25 and 100 mg per kg body weight per day, respectively, and the effects were bactericidal. Both sitafloxacin and ofloxacin exhibited excellent synergistic effects when combined with either rifabutin or KRM-1648, but not with rifampicin. Thus, incorporation of sitafloxacin and rifabutin (or KRM-1648) in the multidrug regimen for treating leprosy patients is suggested.
Subject(s)
Fluoroquinolones/pharmacology , Leprostatic Agents/pharmacology , Leprosy/drug therapy , Leprosy/microbiology , Mycobacterium leprae/drug effects , Rifampin/analogs & derivatives , Animals , Drug Resistance, Bacterial , Drug Therapy, Combination , Female , Fluoroquinolones/administration & dosage , Leprostatic Agents/administration & dosage , Mice , Mice, Inbred BALB C , Mycobacterium leprae/growth & development , Ofloxacin/administration & dosage , Ofloxacin/pharmacology , Rifampin/administration & dosage , Rifampin/pharmacologyABSTRACT
The antimicrobial effects of a new dihydrofolate reductase inhibitor, epiroprim, either singly or in combination with dapsone against Mycobacterium leprae, were evaluated in vivo using a mouse footpad model. When fed to mice at concentration of 0.05% in diet, epiroprim completely inhibited the growth of both dapsone-sensitive and dapsone-resistant strains of M. leprae in the footpads of mice and the effects were bactericidal. To achieve similar effects, the concentration of dapsone in the diet had to be 0.0005 and 0.01%, respectively. When used in combination, the concentrations of the drugs in the diet could be lowered by 50-80% and still achieve bactericidal effects. The data support the earlier results on in vitro studies and suggest the use of epiroprim in the multidrug regimen in the treatment of leprosy.