The effect of urea and the carbamates on bacterial growth
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This project was undertaken to determine the effect of urea and the carbamates on bacterial growth. Urea has been known for a long time. It was the first organic compound to be synthesized in the laboratory. It is cheap, stable and easy to prepare. Ethyl carbamate, like all other carbamates, is an ester of carbamic acid. It was formerly used as an anesthetic agent in humans. It has of late been used in the treatment of leukemia. It is still widely used as an anesthetic agent for laboratory animals. Little is known of the chemistry of higher carbamates. Simple methods of laboratory synthesis have recently been discovered. The bacteriostatic properties of urea were noticed as long ago as 1906. Little attention was paid to the bacteriostatic properties of urea until Symmers and Kirk recommended the use of urea as an antiseptic in 1915. one-half saturated urea solutions are bacteriostatic to a large number of bacteria. Staph. aureus is one of the most resistant organisms to urea. Rabies, poliomyelitis, an yellow fever viruses inactivated immediately by concentrated urea solutions. This is probably due to the fact that urea denatures protein while dissolving it. Concentrations of urea less than 15 percent are not uniformly bacteriostatic in vivo. Those less than 30 percent are not usually bactericidal. Six percent urea is bacteriostatic for E. Coli, D. pneumonia, Strep. hemolyticus, P. vulgaris, E. typhosa, Ps. aeruginosa, S. schottmulleri, and Sh. paradysenteriae (Flexner). Twelve percent urea is necessary to produce a similar effect on Staph. aureus. Exposure to 20 percent urea is bactericidal for these organisms with the exception of Staph. aureus which survives 20 percent urea for 24 hours. The size of the inoculum plays an important part in the degree of bacteriostasis produced by urea. The larger inoculum, the smaller is the bacteriostatic effect. Ureas enhances the effect of the sulfonamides. Whether the enhancement is synergistic or additive is a debatable point. Divergent opinions concerning conjoint action of urea and sulfonamides are probably the result of the use of different experimental conditiobs, e.g., size of inoculum and type of medium. The degree of p-aminobenzoic acid inactivation by urea is directly proportional to the concentration of carbamide. The greater the quantity of urea used, the more intense is the anti-PABA effect. The effect does not usually persist more than 24 hours. Penicillin-urea mixtures, tested on mixed cultures of organisms, brought about complete sterilization of the cultures. Ethyl carbamate is about twice as effective as urea as a bacteriostatic agent. Ethyl carbamate, like urea, has the ability to neutralize the anti-sulfonamide effects of p-aminobenzoic acid. The combination of non-bacteriostatic amounts of ethyl carbamate with non-bacteriostatic amounts of sulfonamide results in results in pronounced inhibition of bacterial growth. There was much controversy caused by attempts to determine whether the effect was synergistic or merely additive. The treatment of mixed infections with ethyl carbamate-sulfonamide mixtures met with great success. The sulfonamides eliminated the Gram-positive organisms while ethyl carbamate eliminated the Gram-negative organisms. Bacteriostatic amounts of ethyl carbamate combined with bacteriostatic amounts of penicillin proved to be very effective in bringing about sterilization of mixed cultures of organisms. No synergism was observed in this case, however. Ethyl carbamate-penicillin mixtures are considered superior to ethyl carbamate-sulfonamide mixtures in the treatment of wound infection. An increase in the number of C atoms in the alkyl chain results in the augmentation of the antibacterial properties of the lower members of the carbamate family. The configuration of the alkyl chain is not important in increasing the antibacterial potency of the chemicals. The higher members of carbamate series of chemicals seem to be just as effective against Gram-positive as Gram-negative organisms. This is in contrast to the action of urea and ethyl carbamate which had little or no effect on Gram-positive organisms. The higher members of the carbamate family are only slightly soluble in water. The higher members of the carbamate series, like urea and ethyl carbamate, exert a neutralizing effect on p-aminobenzoic acid. The anti-PABA persists for only a short time, however. An increase in the length of the alkyl chain in a carbamate results in an augmentation of the ability of the substance to neutralize the action of PABA. The addition of non-bacteriostatic amounts of these carbamates to non-bacteriostatic quantities of sulfonamide suppresses multiplication of bacteria. Urea is non-toxic in the quantities needed in the treatment of wounds. Urea solutions permeate the membranes of all kind of cells. When cells are placed in urea solutions, the concentration within at once becomes the same as without. Thus, urea can never cause hemolysis. Ethyl carbamate in large doses produces pronounced damage of portal vein and sinusoidal capillaries of white rats. Repeated injections of ethyl carbamate can result in a significant augmentation of pulmonary adenomas of mice of the abc strain which normally has a high spontaneous rate for tumors of this type. Pnuemonia with agranulocytosis is a reaction likely to result from treatment with urethane. The bacteriostatic effect of some of the higher members of the carbamate series was tested in our laboratories. These chemicals were found to be highly bacteriostatic for organisms. The common intestinal pathogens are similar to each other in their susceptibility to the higher members of the carbamate family of chemicals. These chemicals were found to be very toxic to mice. Microscopic post-mortem examinations revealed that the liver of the dead mice had turned completely grey or contained large grey patches. Some lung congestion was also noted
Thesis (M.A.)--Boston University, 1950.