CHEMOTHERAPY DEC (NFLX), ofloxacin (OFLX), ciprofloxacin (CPFX) Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterococcus faecali

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CHEMOTHERAPY DEC. 1988 (NFLX), ofloxacin (OFLX), ciprofloxacin (CPFX) Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterococcus faecalis Pseudomonas aeruginosa, Serratia ma-

Fig. 1. Chemical structure of T-3262. Staphylococcus epidermidis Enterococcus faecalis Escherichia coli Klebsiella pneumoniae 20 Enterobacter aerogenes Enterobacter cloa- Citorobacter freundii Proteus nni- Proteus vulgaris Morganella NFLX: norfloxacin OFLX: ofloxacin CPFX: ciprofloxacin Fig. 2. Sensitivity distribution of clinical isolates of Staphylococcus epiderniidis(106 cfu/ml)10 strains. Serratia niarcesens Pseudomonas aeruga nosa E. coil Kp., E. coli ATCC 27166, E. coli NIHJ JC-2, P. mirabilis NFLX: norfloxacin OF LX: ofloxacin CPFX: ci profloxacin Fig. 3. Sensitivity distribution of clinical isolates of Enterococcus faecalis (106 cfu/ml) 12 strains. E. coli, K. pneumoniae, E. aerogenes (Fig. 7)0 C. freundii, P. mirabilis, P. vulgaris

CHEMOTHERAPY

NFLX: norfloxacin OF LX: ofloxacin CI'FX: ci prof loxacin Fig. 4. Sensitivity distribution of clinical isolates of Escherichia coli (106 cfu/ml) 30 strains. NFLX: norf loxacin OFLX: ofloxacin CPFX: ciprofloxacin Fig. 6. Sensitivity distribution of clinical isolates of Enterobacter aerogenes (108 cfu/ml) 6 strains. NFLX:norfloxacin OF LX : ofloxacin CPFX:ci profloxacin Fig. 5. Sensitivity distribution of clinical isolates of Klebsiella pneumoniae (106 cfu/ml) 20 strains. NFLX: norfloxacin OFLX: ofloxacin CPFX: ciprofloxacin Fig. 7. Sensitivity distribution of clinical,isolates of Enterobacter cloacae (108 cfu/ml) 13 strains.

CHEMOTHERAPY DEC. 1988 NFLX: norfloxacin OFLX: ofloxacin CPFX: ciprofloxacin Fig. 8. Sensitivity distribution of clinical isolates of Citrobacter freundii (106 cfu/ml) 19 strains. NFLX: norfloxacin OF LX : ofloxacin CPFX: ciprofloxacin Fig. 10. Sensitivity distribution of clinical isolates of Proteus vulgaris (106 cfu/m1) 10 strains. NFLX: norfloxacin CPFX: ciprofoxacin OF LX : ofloxacin Fig. 9. Sensitivity distribution of clinical isolates of Proteus mirabilis (106 cfu/ml) 20 strains. NFLX: norfl oxacin OF LX: ofloxacin CPFX: ci profl oxacin Fig. 11. Sensitivity distribution of clinical isolates of Morganella morganii(106cfu/m1)10 strains.

Table 2. Case summary of prostatic tissue and serum levels of T-3262 after oral administration at 150mg (fasting) All patients are cases of benign prostatic hypertrophy P/S : Prostatic tissue level/serum level Ccr : Creatinine clearance NFLX: norfloxacin OFLX: ofloxacin CPFX: ciprofloxacin Fig.12. Sensitivity distribution of clinical isolates of Serratia marcescens (106cfu/mI)19 strains. NFLX: norfloxacin OF LX: ofloxacin CPFX: ci profloxacin Fig. 13. Sensitivity distribution of clinical isolates of Pseudomonas aeruginosa (106 cfu/mi) 16 strains.

CHEMOTHERAPY DEC. 1988 Table 3. Case summary and prostatic fluid and serum level of T-3262 after oral administration at 150mg (Non-fasting)

CHEMOTHERAPY

CHEMOTHERAPY DEC. 1988

VOL.36 S-9

CHEMOTHERAPY DEC. 1988 Table 6. Overall clinical efficacy of T-3262 in acute uncomplicated cystitis Table 7. Overall clinical efficacy of T-3262 in complicated UTI

VOL.36 S-9 Table 8. Overall clinical efficacy of T-3262 classified by the type of infection Table 9. Bacteriological response to T-3262 in acute uncomplicated cystitis *Persisted: Regardless of bacterial count

CHEMOTHERAPY DEC. 1988 Table 10. Bacteriological response to T-3262 in complicated UTI * Persisted : Regardless of bacterial count Table 11. Strains* appearing after T-3262 treatment in complicated UTI * Persisted: Regardless of bacterial count

VOL. 36 S-9 All cases are normal volunteers Pf/S: Prostatic fluid level/ Serum level Fig. 14. Prostatic fluid and serum level of T-3262 and Pf/S ratio after oral administration at 150 mg (Non-fasting). All cases are normal Pf/S:Prostatic volunteers fluid level/serum level Fig. 15. Relationship between MIC and prostatic uid level of T-3262 after oral administration at 150 mg fl (Non-fasting). motherapy 34: 408 `441, 1986 4) MEARES E M STAMEY T A: The diagnosis and management of bacterial prostatitis. Brit J Urol 44: 175 `179, 1972

CHEMOTHERAPY DEC. 1988 BASIC AND CLINICAL STUDIES ON T-3262 IN UROLOGY MASAYA TSUGAWA, DAISUKE YAMADA, YOSHITSUGU NASU, MIKI0 KISHI HIROMI KUMON and HIROYUKI OHMORI Department of Urology, Medical School, Okayama University (Director : Prof. H. OHMORI) 2-5-1 Shikada, Okayama-shi, Okayama 700, Japan KATSUICHI NANBA Department of Urology, Okayama City Hospital KATSUYOSHI KONDO Department of Urology, Okayama Red Cross Hospital YASUHIRO KATAYAMA Department of Urology, Tamano City Hospital TERUAKI AKAEDA Department of Urology, Tsuyama Central Hospital NOBUYUKI AKAZAWA Department of Urology, Onomichi City Hospital T-3262, a new pyridone-carboxylic acid, was evaluated basically and clinically in the urological field. 1) Minimal inhibitory concentrations (MICs) of T-3262 were compared with those of norfloxacin, ofloxacin and ciprofloxacin using 189 clinical isolates from urinary tract infections (UTI). The antibacterial activity of T-3262 was as high as or even higher than those of the:three other drugs against all species studied. 2) The concentration of T-3262 in the prostate after oral administration of 150 mg was studied. The concentration in the prostatic tissue, 2 and 4 hours after administration, was 0. 120 }0. 075,aglg (mean LF:SE) and 0. 245±0. 079 peg, respectively. Similarly, the concentration in the prostatic fluid, 1, 2 and 4 hours after administration, was O. 047+0. 014,ug/m1, 0. 111 }0. 080 pg/mi and 0. 033 }0. 014 respectivery. 3) Forty-one patients with UTI were treated by oral administration of T-3262 at a dosage of 75 or 150 mg:two or three times daily for 3-14 days. According to the criteria of the Japanese UTI Committee, the overall clinical efficacy rate was 100 % (5/5) in acute uncomplicated cystitis and 60. 0% (15/25) in complicated UTI. 4) No drug-related side effects, including abnormal laboratory findings, were observed in any of the 40 cases.

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