Carumonamの泌尿器科学領域における基礎的, 臨床的検討

Carumonam is a new monocyclic β-lactam antibiotic, characterized by its potent antimicrobial activity against almost all Gram-negative rods but only weak activity against Gram-positive cocci.<BR>In a recent, preclinical study of carumonam, we administered 1 g of the drug and the same dose of cefoperazone to four healthy adult male volunteers by i. v. drip over 1 h, on a cross-over design, and compared changes in the concentrations of the drugs in the blood and their recovery rates in the urine by bioassay and HPLC during the following 8 h.<BR>In a clinical study of the drug, we administered 1 g of carumonam twice daily by i. v. drip chiefly to patients with chronic complicated urinary tract infection, to evaluate its efficacy, utility and safety.<BR>The study of the absorption and excretion of the drugs revealed that there was no great difference between the data of the bioassay and those of HPLC; that the maximum concentration in the blood was 70.3 μ/ml for carumonam and 141μ/ml for cefoperazone, and the blood half-life was 1.23 h and 1.90 h, respectively, and that the urinary recovery rate during the first 8 h was 83.0% for carumonam and 20.7% for cefoperazone.<BR>Of the fourteen patients enrolled in the clinical study, 12 met the Japanese UTI comittee's criteria for drug efficacy evaluation, and the response to carumonam was excellent in 7, good in 3 and poor in 2 out of the 12, with a response rate of 83%.<BR>This high response rate probably resulted from the subjects including no patients with polymicrobial infections. On the other hand, bacteriological studies revealed that 2 of 5 strains of Pseudomonas aeruginosa persisted, while 10 (83%) of 12 pathogens were eradicated.<BR>The response to carumonam among other patients was: excellent in 2 patients with acute simple cystitis, good in 2 with acute prostatitis and in 1 with acute epididymitis. No side-effects of carumonam were observed. Laboratory studies revealed the onset of leukopenia in one patient, though medication with carumonam could be continued.<BR>Our results suggested that carumonam would be useful in treating selected patients with urinary tract infections.