Sulfamethazine: In Vitro Action on Enteric Pathogens as Compared with Sulfadiazine and Sulfamerazine.

New sulfonamides are usually tested against bacteria or diseases wherein the older drugs work satisfactorily. There seems to be little advantage in testing new drugs only against those bacteria in which older sulfonamides have already proved their worth. Since the older sulfonamides exert little action on diseases caused by some gram-negative organisms, it seemed advisable to attempt to find one which might prove efficacious in treatment of typhoid and paratyphoid infections. Four sulfonamides which were tested previously (Schweinburg and Yetwin, 1944) were not satisfactory so we decided to investigate the potentialities of sulfamethazine.' We do not overestimate conclusions as to clinical application that may be drawn from test tube experiments. Although some believe there is no quantitative relationship between in vitro and in vivo action (Marshall, Litchfield, White, Bratton, and Shepherd, 1942), other recent papers reveal a surprising parallelism between resistance in vitro and unsuccessful treatment (Cohn, Steer, and Seijo, 1942; Spink and Vivino, 1944; Winchester and Whittle, 1944). If a drug is an effective bactericidal and bacteriostatic agent in the test tube, it may or may not be effective in vivo. But it cannot be expected that a drug ineffective against a certain bacterium in vitro will prove successful in combating a disease caused by that organism. Two new sulfa drugs, sulfapyrazine and sulfamethazine, are now in use, both apparently effective against gram-positive and gram-negative cocci. At the present time the output of sulfapyrazine is apparently limited and we therefore regret our inability to obtain it for examination upon the enteric organisms. The other sulfonamide, sulfamethazine (called sulphamezathine by the English), is dimethylsulfadiazine and consequently not only related to sulfadiazine but also to sulfamerazine, which is monomethylsulfadiazine. The in vitro action of sulfamethazine closely resembles that of sulfapyridine when tested against streptococci and pneumococci (Rose, Martin, and Bevan, 1943). Clinical trials with both drugs have shown good results in dysentery but no effect against the Salmonella infections (Hardy and Watt, 1944). Sulfamethazine is probably the best of all sulfonamides in the treatment of pneumonia (Page, 1944); it apparently has some advantages over the other sulfonamides now in use (Rose, Martin,