Inhibition by streptovaricins of Rauscher leukemia virus splenomegaly.

Streptovaricins (Sv), ansa macrolide antibiotics, inhibited Rauscher leukemia virus (RLV) splenomegaly by 25-50%. All streptovaricins tested were effective when administered orally either by diet ad lib or by intubation from infection to time of killing. When delivered by intubation, Sv was measurable in plasma for up to 6 h. SvC, at 300 mg/kg/day, reduced mean spleen weight of infected mice from 478 plus or minus 51 (SE) mg to 300 plus or minus 55 (SE) mg. Rifampicin, at 250 mg/kg/day, had no similar activity. Decrease in caloric intake and in body-weight gain also resulted in an inhibition of RLV splenomegaly; although Sv-treated mice gained weight, the increase was usually slightly less than controls. However, mice treated with a Sv diet for a week prior to infection, after an initial period of weight loss, gained at a rate equivalent to control group, and when killed had a marked reduction in splenomegaly. The selectivity of streptovaricins and specificity for viral events was suggested by several observations: (1) Splenomegaly and mortality, induced by L1210 or a non-infective transplantable tumor of RLV origin, was not inhibited. (2) No inhibition of normal hematopoietic spleen colonies was observed. (3) Host immune responses, including cellular and humoral immunity and interferon production and action, were not inhibited. Thus, although the effect of slightly decreased weight and intake could not be unequivocally established, the findings were most compatible with a selective inhibition of RLV splenomegaly by Sv.

Kinetic testing of drugs against Mycobacterium leprae in mice. Activity of cephaloridine, rifampin, streptovaricin, vadrine, and viomycin

A series of drugs that had been found active against Mycobacterium leprae in mice by the continous method of drug administration was tested by the kinetic method. Vadrine and vyomivin were found inactive. Cephaloridine, streptovaricin, and rifampin gave bactericidal-type results. In a second experiment, rifampin was found to have distinct bactericidal effect when given for only 2 days. The plasma levels of rifampin that were associated with bactericidal effect in mice were in the range reported for man receiving acceptable dosages of rifampin. Cephaloridine and, especially, rifampin merit further investigation in clinical trials in leprosy patients, either as single drugs or in combination with other active drugs. The combination of rifampin and dapsone (DDS) or acedapsone (DADDS) appear to provide the advantages of tboth drugs.