Antagonism of Anti-sulfonamide Effect of Methionine,and Enhancement of Bacteriostatic Action of Sulfonamide by Urea. ∗

Discussion and Conclusions

Whether the urea effect is an enhancement of the sodium sulfadiazine effect alone, or a neutralization of the methionine effect, or both, cannot be established from this preliminary data, although we are investigating this point further. However, under the conditions of our experiment, the following conclusions seem to be justified:

1. With the concentration of sodium sulfadiazine used, approximately 80% inhibition of growth of E. coli in synthetic medium occurred. 2. In the concentrations used, methionine and urea alone, or in combination, displayed no effect on the growth of the test organism. 3. Methionine almost completely inhibited the bacterio-static effect of sodium sulfadiazine, thus confirming previous reports. 4. Urea and sodium sulfadiazine together showed a greater growth inhibitory effect than the latter alone. 5. Urea neutralized this inhibitory effect of methionine on sodium sulfadiazine and in conjunction with the sulfonamide, even though in the presence of methionine, displayed a greater growth inhibitory effect than the sulfadiazine alone.

Work is in progress to elucidate the action of urea on the effect of other inhibitors and on other sulfonamides. We are also investigating the action of urea on sulfonamide-fast pathogens in synthetic medium, and on the bacteriostatic action of sulfonamides in experimental and clinical treatment of infected wounds.

Clinical experience 9 has confirmed the work of Holder and Mac-Kay, and we feel that the beneficial action of urea in combination with the sulfonamides in the treatment of infections may be due partly to the effects described in this paper.