Chloromycetin: Biological Studies

Abstract

The antibiotic, chloromycetin, is produced by a Streptomyces sp. in aerated, submerged culture in various organic media and assayed turbidimetrically against Shigella paradysen-teriae Sonne. The crystalline compound is inactive in vitro against protozoa and fungi, moderately active against Gram-positive and acid-fast organisms and active against Gram-negative organisms and Borrelia recurrentis. In exptly. infected animals chloromycetin was ineffective against avian malaria, rabbit syphilis and type A influenza, St. Louis encephalitis, and fixed rabies viruses, moderately effective against Klebsiella pneumonia and S. paradysenteriae (Sonne and Flexner) septicemias, and remarkably effective against epidemic typhus in embryonated eggs. As little as 17 7 adm. 3 days post-infection to chick embryos infected with Rickettsia prowazeki caused a prolongation of life. Larger doses caused increasingly greater prolongation of life and 667 [gamma]/egg in divided doses allowed 33.5% survival. The LD50 for mice intraven. is 245 mg./kg.; orally it is >[gamma] g./kg. Oral adm. of chloromycetin appears more practicable than intramusc. adm., as the former route circumvents the anemia and local tissue damage associated with the latter route. In dogs, 2 hr. serum concs. of chloromycetin were similar after parenteral or oral adm. (1 to 29 7/ml. and 6-19 [gamma]/ml., respectively); 18-hr. serum levels were usually <2 [gamma]/ml. After single doses of chloromycetin in dogs, <10% of the administered dose was accounted for in the urine by microbiological assay, indicating extensive in-activation or excretion by other routes.