Keiichi Munakata

A Newly Designed Model for Infection-Induced Bladder Stone Formation in the Rat

A newly designed urolithiasis model for rats, inducing a mild urinary tract infection, exhibiting reduced renal damage without pyelonephritis and causing reliable stone formation, was established. This was accomplished by implanting a zinc disc in the bladder and then performing transvesical inoculation of Proteus mirabilis into the bladder. Five days after challenge with 10(7) colony forming units (CFU) of P. mirabilis in each rat, the number of organisms in the bladder urine reached a level of over 10(5) colony forming units per ml. The infection was mostly restricted to the urinary tract organs. Infectious bladder stones were formed 5 days after infection and developed day by day, weighing 88.3 +/- 18.8 mg. on the 21st day. Blood urea nitrogen values stayed in the normal range in all test animals during this experiment. The main composition of the stones formed was shown to be struvite (MgNH4PO4 X 6H2O).

Therapeutic effects of cefluprenam (CFLP) on polymicrobial infections associated with Enterococcus faecalis in rat pyometra model

Enterococcus faecalis plays an important role as one of the pathogens in polymicrobial infections. We evaluated the efficacy of cefluprenam (CFLP) using a polymicrobial pyometra of a model rat. Rats were infected with a mixed intrauterine inoculation of E. faecalis plus either Bacteroides fragilis or Prevotella bivia (minimal inhibitory concentration of CFLP: E. faecalis, 3.13 mug/ml; B. fragilis, 3.13 mug/ml; P. bivia, 3.13 mug/ml). Immediately after inoculating 10(5) cfu/rat of each organism, CFLP (either 40 mg/kg, i.v., q.i.d. for 5 days or 80 mg/kg, i.v., b.i.d. for 5 days) was administered. The intrauterine inflammatory change and bacterial count in the treated group were compared with those in the non-treated control group. CFLP significantly (P < 0.01) decreased the bacterial counts except for B. fragilis in the regimen of 80 mg/kg, b.i.d. However, the regimen of 40 mg/kg, q.i.d. significantly (P < 0.05) reduced the bacterial counts more than did that of 80 mg/kg, b.i.d. CFLP proved to demonstrate a good tissue concentration above 3 mug/g for 1 h. These results suggest that CFLP in a more divided dose is efficacious for the treatment of polymicrobial infections associated with E. faecalis in pyometra.

Evaluation of the Usefulness of a Novel Injectable Cephalosporin, E1040, and Ceftazidime for Management of Complicated Urinary Tract Infections Caused by Pseudomonas aeruginosa and Proteus mirabilis by Using the Rat Urolithiasis Model

A novel injectable cephalosporin, E1040, significantly eradicated Pseudomonas aeruginosa from the urine, in contrast to ceftazidime, in rats with complicated P. aeruginosa urinary tract infections associated with urinary stones, suggesting that E1040 is a prospective therapeutic agent in the management of refractory Pseudomonas urinary tract infections.