A radiometric method for predicting effectiveness of chemotherapeutic agents in murine leprosy.
A simple radiometric method has been developed for evaluating the effect of drugs on the metabolism of M. lepraemurium. The method is based on the measurement of the 14CO2 produced through bacterial metabolism of acetate-U-14C. Seventeen drugs were tested: bacitracin, cephaloridine, chloramphenicol, cycloserine, dactinomycin, DDS, ethionamide, INH, kanamycin, methenamine mandelate, nitrofurantoin, oxacillin, polymyxin B, rifampicin, streptomycin, sulfadimethoxine and vancomycin. The drugs which caused most marked inhibition were chloramphenicol, INH, ethionamide and nitrofurantoin in order of increasing effectiveness. The radiometric study which is completed in 15 days permits direct study of the drug effect on the metabolism of M. lepraemurium and a more rapid screening of antileprosy drugs than has previously been possible. Currently, these observations are being extended to studies of the structure-activity relationships of antileprosy drugs and the metabolism and drug susceptibility of M. leprae in vitro.
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001414:Bacitracin / Q000494:pharmacology; D002509:Cephaloridine / Q000494:pharmacology; D002701:Chloramphenicol / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003622:Dapsone / Q000494:pharmacology; D005000:Ethionamide / Q000494:pharmacology; D007538:Isoniazid / Q000494:pharmacology; D007612:Kanamycin / Q000494:pharmacology; D008709:Methenamine / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009164:Mycobacterium Infections / Q000188:drug therapy*; D009167:Mycobacterium lepraemurium / Q000187:drug effects*; D009582:Nitrofurantoin / Q000494:pharmacology; D010068:Oxacillin / Q000494:pharmacology; D011113:Polymyxins / Q000494:pharmacology; D011874:Radiometry; D012293:Rifampin / Q000494:pharmacology; D013307:Streptomycin / Q000494:pharmacology; D013412:Sulfadimethoxine / Q000494:pharmacology; D014640:Vancomycin / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D011113:Polymyxins; D001414:Bacitracin; D003609:Dactinomycin; D013412:Sulfadimethoxine; D007612:Kanamycin; D002701:Chloramphenicol; D014640:Vancomycin; D003622:Dapsone; D009582:Nitrofurantoin; D008709:Methenamine; D002509:Cephaloridine; D005000:Ethionamide; D010068:Oxacillin; D007538:Isoniazid; D012293:Rifampin; D013307:Streptomycin