BASIC AND CLINICAL STUDIES WITH PIVMECILLINAM IN URINARY-TRACT INFECTIONS

Abstract

1) Antibacterial activities
For 22 standard strains preserved in our department and 513 strains of clinical isolates (Escherichia coli, 81 strains; Klebsiella aerogenes, 81 strains; Serratia marcescens, 212 strains; Proteus vulgaris, 22 strains; Proteus mirabilis, 50 strains; Proteus rettgerii, 14 strains; Proteus inconstans, 11 strains and Proteus morganii, 42 strains), MICs of pivmecillinam, mecillinam and ampicillin were determined by the standard method of Japan Society of Chemotherapy. Mecillinam showed more potent antibacterial activities than ampicillin against E. coli, Klebsiella aerogenes, Proteus vulgaris and Proteus mirabilis, but was less potent than ampicillin against gram-positive cocci. MIC of mecillinam varied with inoculum sizes and MIC with 108 cells/ml inoculum size was considerably lower than with 10⁸ cells/ml.
2) Absorption and excretion
Three healthy adults were orally given 100 mg (as mecillinam) ofpivmecillinam. Peak plasma mecillinam level reached 0.54-0.95 μg/ml one to two hours after administration. No mecillinam was detected in the plasma 6 hours after administration. The mean 6-hour urinary recovery was 38.7%.
3) Clinical results
Six cases with acute cystitis, 2 cases with chronic cystitis and 2 cases with chronic pyelonephritis were given pivmecillinam in doses of 300-400 mg per day for 7-21 days. The response was excellent in 7 cases, good in 1, poor in 2. No abnomal findings were demonstrated with hematological examination, blood chemistry test and urine analysis except slight increase of total serum bilirubine (1.0 mg/dl→1.3 mg/dl) in one case, which was rapidly normalized.