Methenamine and its salts as urinary tract antiseptics: variables affecting the antibacterial activity of formaldehyde, mandelic acid, and hippuric acid in vitro.

The activities of formaldehyde and of mandelic and hippuric acids, alone and in combination, have been tested against some 300 strains of bacteria typical of those causing urinary tract infections. In a chemically defined medium, which resembles urine in many respects, formaldehyde had a mean minimal inhibitory concentration of 13 mug per ml. Activity was several fold lower in media (nutrient agar and tryptic soy agar) that contained significant amounts of protein. The activity of formaldehyde is virtually unaffected by pH in the range of 5 to 8. Mandelic and hippuric acids (2 mg per ml) have limited antimicrobial activity at acid pH values only. The combination of formaldehyde with mandelic acid (2 mg per ml) was additive, most markedly at pH 5; the formaldehyde-hippuric acid combination, however, did not appear to be additive. Our findings suggest that, at pH values between 5 and 6, an antibacterial concentration of formaldehyde will be generated from methenamine within approximately 1 hr after being excreted into the urine.