Abstract
We investigated the influence of urine components, such as pH, magnesium concentration and calcium concentration, on the antimicrobial activity of pazufloxacin (PZFX), and the influence of PZFX on the bactericidal activity of leukocytes. We also studied the clinical efficacy of PZFX for urinary tract and genital infections in order to clarify its usefulness in such infections.
1. Influence of urine pH and cations on antimicrobial activity of PZFX We investigated the antimicrobial activity of PZFX in human urine and the influence of urine components (pH, magnesium concentration and calcium concentration) on the antimicrobial activity of PZFX. Two bacterial strains, Escherichia coli NIHJ JC-2 and Pseudomonas aeruginosa 18S, were tested. The MBC of PZFX in urine was higher than in Miieller-Hinton broth against these two strains. However, no influence of urine components on the MBC of PZFX was seen in E. coli. On the other hand, the MBC of PZFX against P. aeruginosa was low when urine pH was high.
2. Influence of PZFX on bactericidal activity of leukocytes Polymorphonuclear leukocytes (PMNs) and monocytes isolated from a healthy volunteer were stimulated by phorbol myristate acetate (PMA) or opsonised zymosan in the presence or absence of PZFX, and the superoxide anion generation of PMNs and monocytes was measured by the chemiluminescence method.
The bactericidal activity of PMNs was enhanced by PZFX.
3. Clinical study of PZFX in urinary tract and genital infections PZFX was administered to eighteen patients with urinary tract and genital infections. The clinical efficacy of PZFX was evaluated by determining symptoms, pyuria, bacteriuria and blood test results before and after the administration of PZFX. One patient with acute uncomplicated cystitis and two patients with acute prostatitis showed excellent response, and one patient with acute uncomplicated pyelonephritis showed moderate response. Thirteen patients with chronic complicated urinary tract infections were evaluated according to the criteria of the UTI Committee, and the overall efficacy rate was 84.6%(excellent: 30.8%, moderate: 53.8%, poor: 15.4%). 23 strains of 9 species were isolated from the patients with chronic complicated urinary tract infections, and 19 strains were eliminated. As to side effects, one case of slight dizziness was observed. No abnormal laboratory findings were caused by PZFX.
These results indicated that PZFX enhances the in vivo bactericidal effect of leukocytes and is a useful antimicrobial agent for urinary tract and genital infections. We should examine the clinical effect of PZFX on urinary tract infections, paying attention to the urine pH of the patients.
