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Comparisons of Sulfisoxazole with Sulfadiazine, and Thiocymetin with Chloramphenicol, in Chemotherapy of Experimental Plague in Mice

In broth cultures of 10 strains of Pasteurella pestis, 3,4-dimethyl-5-sulfanilamido-isoxazole (Gantrisin, sulfisoxazole) in concentrations of 8 to 16 times less than that of 2-sulfanilamidopyrimidine (sulfadiazine) produced a similar degree of bacteriostasis. Against the same strains of plague, chloramphenicol was 16 to 32 times more inhibitory than thiocymetin. Chloramphenicol exerted a marked antibacterial action at a concentration of 2.5 microgram/ml. as compared with about the same action for 1.3 mg./ml. of sulfisoxazole. Thus in vitro chloramphenicol was about 20 times more potent than thiocymetin, 500 times more than sulfisoxazole, and 5,000 times more than sulfadiazine. Since the mechanism of action of the synthetic antibiotics differs from that of the sulfonamides, the two types of drugs are not comparable. This difference is illustrated by the fact that sulfadiazine proved to be the most effective among these chemicals for experimental plague prophylaxis in laboratory mice, whereas chloramphenicol was the best therapeutic agent. The in vivo order of efficacy was chloramphenicol, sulfadiazine, thiocymetin, and sulfisoxazole. The lower therapeutic value of sulfisoxazole compared with sulfadiazine, and of thiocymetin compared with chloramphenicol is probably due to more rapid excretion by the kidneys.