USE OF RIFABUTIN IN TREATMENT OF SYSTEMIC MYCOBACTERIUM-PARATUBERCULOSIS INFECTION IN MICE

BALB/c mice were infected intraperitoneally with Mycobacterium paratub erculosis and, after allowing the infection to progress for 30 days, w ere treated with rifabutin at 0, 12.5, 25, and 50 mg/kg of body weight . Rifabutin was administered in drinking water under conditions of wat er deprivation, whereby the entire daily dose was delivered within a 1 -h period. Animals were killed at biweekly intervals from time zero of treatment to 180 days. Spleens and livers from each animal were exami ned by quantitative bacteriologic culture and histopathology. Restrict ed water availability was found to be a viable alternative to daily ga vage for single-dose bolus administration. Infection, as assessed by b acterial counts, was reduced only in animals that received 50 mg of ri fabutin per kg. In these animals, bacterial counts in the liver and sp leen were reduced from 7.2 x 10(5) +/- 4.1 X 10(4) and 6.5 x 10(5) +/- 4.1 X 10(4) to 3.0 x 10(3) +/- 1.8 x 10(2) and 3.1 x 10(3) +/- 2.2 x 10(2), respectively, over the 6-month treatment period. Rifabutin may be an appropriate chemotherapeutic drug for long-term treatment of M. paratuberculosis infection and should be considered in any multidrug r egimen.