Activities of new macrolides and fluoroquinolones against Mycobacterium ulcerans infection in mice

Mice infected in the left hind footpad with 5 log(10) acid-fast bacilli of Mycobacterium ulcerans were divided into an untreated control group and 17 treatment groups that received one of the following regimens for 4 weeks (a ll doses in milligrams per kilogram): 100 mg of azithromycin (AZM), 100 mg of clarithromycin (CLR), or 50 mg of AZM for a duration of 5 days a week (d aily), three times a week, or once weekly. In addition, the following regim ens were administered daily: 100 mg of telithromycin (TLM), sparfloxacin (S PX), or moxifloxacin (MOX); 200 mg of levofloxacin (LVX); 100 mg of strepto mycin (STR) or amikacin (AMK); 10 mg of rifampin (RIF); and the combination of 10 mg of RIF and 100 mg of AMK (RIF+AMK). After completion of treatment , mice were observed for 30 weeks. The effectiveness of treatment regimens was assessed in terms of the delay in median time to footpad swelling in tr eated mice compared with that in the untreated controls. Clear-cut bacteric idal activity, i.e., an observed delay in footpad swelling that exceeded th e period of treatment, was observed in the STR-, AMK-, and RIF+AMK-treated mice. However, all mice treated with either AMK or STR alone had swollen fo otpads before the end of the 30-week observation period, suggesting regrowt h of M. ulcerans. In contrast, 50% of the mice treated with the RIF+AMK com bination exhibited no lesion even after 30 weeks, suggesting cure. The rema ining regimens could be assigned to one of three groups: (i) no activity (5 0 mg of AZM, 100 mg of AZM thrice weekly, TLM, and LVX); (ii) bacteriostati c activity, i.e., a delay in footpad swelling shorter than the 4-week treat ment duration (100 mg of AZM daily or once weekly, CLR thrice or once weekl y, and MOX); or (iii) weak bactericidal activity (CLR daily and SPX). The R IF+AMK combination and possibly RIF+STR warrant further study for the treat ment of M. ulcerans infection in humans.