Activity of ofloxacin and pefloxacin against Mycobacterium leprae in mice.

The fluorinated quinolones are potent antibacterial compounds active against both gram-negative and gram-positive bacteria (1, 3-5, 11-13). Some are also active against mycobacteria in general (3, 9, 10, 13) and Mycobacterium tuberculosis in particular (1; unpublished observations). In view of the limited number of drugs active against Mycobacterium leprae, it was of interest to test some of these drugs against M. leprae in the mouse footpad model (7). M. leprae L6382 and L90, isolated in our laboratory in 1963 (6) and 1980, respectively, from previously untreated patients infected in Rwanda and Mali and continuously passaged in the mouse footpad were used. Ofloxacin was a gift from Hoechst, Brussels, Belgium, and pefloxacin was a gift from Rhone-Poulenc, Brussels, Belgium. The anti-M. leprae activity of the drugs was determined by the proportional bactericidal test (2). Groups of five mice were inoculated in the left hind footpad with 104, 103, 102, and 10 acid-fast bacilli. One group of mice served as untreated controls; the others were given the drugs by stomach gavage in 0.5-ml quantities at the dosages and intervals indicated in Tables 1 and 2. Treatment lasted from day 35 until day 154. At 1 year after infection, the mice were killed, and the acid-fast bacilli were counted in individual footpads. Statistical calculations were performed as described by Shepard (7). The results are shown in Tables 1 and 2. Ofloxacin was bactericidal against M. leprae when administered five times a week at dosages of 150, 100, and even 50 mg/kg (body weight). Pefloxacin showed no activity when administered at 100 mg/kg 5 days a week or at 150 mg/kg at lower frequencies. However, the drug showed activity at 300