Activities of several antimicrobials against Mycobacterium ulcerans infection in mice

Mycobacterium ulcerans inoculated into the footpads of mice at 6 x 10(3) CF U was shown to have a generation time of 6.5 days when estimated from weekl y changes in microscopic counts of acid-fast bacilli (AFB) and 7.5 days whe n calculated from actual CFU enumerated on Lowenstein-Jensen egg medium inc ubated at 32 degrees C. Footpads became swollen at week 10 (W10) after infe ction, and all infected control mice were dead at W15 after infection. Dail y (5 days/week) treatment with 100 mg of clarithromycin (CLR)/kg of body we ight beginning the day after infection prevented swelling of footpads at W1 0, When initiation of treatment was delayed until obvious footpad swelling was observed, there was a reduction in both the increase in AFB counts and deterioration of swollen footpads and also a prolonged survival of the mice to W18. Mice infected in the hind footpads with 5 x 10(5) CFU of M. ulcera ns were divided into an untreated control group and six treatment groups th at received one of the following therapies for 8 weeks: 100 mg of CLR/kg, 2 5 mg of minocycline (MIN)/kg, 50 mg of sparfloxacin (SPX)/kg, 10 mg of rifa mpin (RIF)/kg, 10 mg of rifabutin (RBT)/kg, or 100 mg of amikacin (AMK)/kg, After completion of therapy, treated animals were observed for an addition al 17 weeks. All control mice and mice treated with CLR, MIN, or SPX exhibi ted swollen footpads during the observation period. In contrast, of those a nimals treated with RIF, RBT, or AMK, none had footpad swelling and all ino culated cultures done after the W17 observation remained negative. These re sults suggest that RIF, RBT, and AMK may be effective in the treatment of h uman infection with M, ulcerans.