Since the advent of chemotherapy in the management of infections of the urinary passages, several milestones in its progress can be marked. As recently as 1895, when Nicolaier first instituted the use of methenamine for patients with such infections, the treatment consisted of alkalization when the urine was acid and acidification when it was alkaline. In 1931, the ketogenic diet was introduced, and betaoxybutyric acid produced physiologically by the body gave urine definite bactericidal properties when its acidity ranged between pH 5 and 5.5. The difficulty of management and the lack of economy of the ketogenic diet have been obvious, and Rosenheim's introduction of mandelic acid in place of beta-oxybutyric acid was a great step forward. However, mandelic acid in large amounts is likely to cause digestive upset and occasional hematuria. Furthermore, when the kidneys are damaged or when the infection is one of those producing a persistent strongly alkaline
HELMHOLZ HF, SUNG C. BACTERICIDAL ACTION OF PENICILLIN ON BACTERIA COMMONLY PRESENT IN INFECTIONS OF URINARY TRACT: WITH ESPECIAL REFERENCE TO STREPTOCOCCUS FAECALIS. Am J Dis Child. 1944;68(4):236–242. doi:10.1001/archpedi.1944.02020100008002
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