Proteus vulgaris urinary tract infections in rats; treatment with nitrofuran derivatives.

Ascending urinary tract infections with stone formation have been produced experimentally in rats, using a modification of the method of Vermuelen & Goetz (1954a, b). A zinc disc infected with a culture of Proteus vulgaris was inserted into the bladder by suprapubic cystotomy under ether anaesthesia. The pH of the urine rises from 6.9 to 8 or 9 and calculi develop in the bladder within a few days of infection. The bladder and ureters become swollen, distended and inflamed, and renal abscesses develop. Death from renal failure generally occurs within 10 days of infection. Oral treatment with nitrofurantoin was commenced three days after infection and continued for one month. This arrested the initial rise in urine alkalinity and stone formation, and few, if any, macroscopic lesions were found at post-mortem examination. Of nine nitrofuran derivatives examined for activity against this infection several showed slight activity, but only one, N-(5-Nitrofurfurylidene)-gamma-butyric acid, was as active as nitrofurantoin when given at four times the dose, but it was also one-third as toxic. It is concluded that this technique is suitable for the examination of potential urinary antiseptics.