Pipemidic acid, 8-ethyl-5, 8-dihydro-5-oxo-2- (1-piperazinyl) -pyrido [2, 3-d] pyrimidine-6-carboxylic acid, is a new derivative of piromidic acid. It was active against gram-negative bacteria including Pseudomonas aeruginosa as well as some gram-positive bacteria. Its potency against gram-negative bacteria was generally greater than that of piromidic acid, nalidixic acid and cephalexin. Crossresistance was not observed between pipemidic acid and various antibiotics, and most of bacteria resistant to piromidic acid and nalidixic acid were moderately susceptible to pipemidic acid.
The activity of pipemidic acid was scarcely affected by the addition of serum, sodium cholate or change of medium pH, but was subject to the influence of inoculum size. Its action was bactericidal above minimal inhibitory concentrations. Additive effect was observed when pipemidic acid was used in combination with carbenicillin or gentamicin. Pipemidic acid was effective by the oral route on various experimental infections in mice. Its in vivo efficacy against gram-negative bacteria was generally better than that of piromidic acid, nalidixic acid, cephalexin, ampicillin and carbenicillin. The infection with bacteria resistant to piromidic acid and nalidixic acid was successfully treated with pipemidic acid.
In Pseudomonas aeruginosa infections, orally administered pipemidic acid was more effective than subcutaneously injected carbenicillin.