In 1942 Tsuchiya1 and his co-workers reported in vitro experiments with urea and the sulfonamide compounds which indicated that the inhibitory effect of sulfadiazine on the growth of Escherichia coli is significantly increased by the presence of urea, even when methionine, a sulfonamide inhibitor, is present.
They extended their observations to other sulfonamide compounds, using para-aminobenzoic acid as the sulfonamide inhibitor, and also showed that three strains of sulfathiazole-resistant staphylococci in a synthetic medium were susceptible to urea-sodium sulfathiazole combinations. They attributed this beneficial effect of urea to its inhibition of the sulfonamide inhibitors and to an enhancement of the bacteriostatic action of the sulfonamide compounds.
The development of sulfonamide resistance by bacteria has become significant, and any agent which may overcome this resistance may play an increasingly important role. McLeod2 showed that the development of sulfapyridine fastness in a strain of Pneumococcus type I is accompanied by
LA LONDE AA, GARDNER WJ. EFFECT OF UREA ON BACTERICIDAL ACTION OF SULFONAMIDE DRUGS: Report of Five Cases of Bacterial Meningitis. JAMA. 1948;138(6):406–408. doi:10.1001/jama.1948.02900060010005
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