The bacterial strains isolated from patients diagnosed as having urinary tract infections (UTIs) in 10 institutions in Japan were supplied between the period of August 2000 and July 2001. Then, the susceptibilities of them to many kinds of antimicrobial agents were investigated. The number of them were 511 strains. The breakdown of these strains was Gram-positive bacteria as 29.0% and Gram-negative bacteria as 71.0%.
Susceptibilities of these bacteria to antimicrobial agents were as follows; vancomycin (VCM), ampicillin (ABPC) and imipenem (IPM) showed strong activities against Enterococcus faecalis. No increase in lowsusceptible strains of E. faecalis observed against these antimicrobial agents. VCM showed a strong activity against MRSA preventing growth of all strains with 1μg/ml. In addition, the activity of arbekacin (ABK) was strong with the MIC₉₀ of 2μg/ml against MRSA and prevented growth of all strains with 4μg/ml. ABK showed a strong activity against Staphylococcus epidermidis preventing growth of all strains with 0.5μg/ml. ABPC, cefotiam (CTM) and cefozopran (CZOP) also showed a relatively strong activity against S. epidermidis (MIC₉₀: 4 to 8μg/ml). Against Escherichia coli, carbapenems showed high activities: meropenem (MEPM) prevented growth of all strains within 0.125μg/ml; IPM prevented growth of all strains with 0.25μg/ml. CZOP and CTM also showed strong activities against E. coli: MIC₉₀ of CZOP was within 0.125μg/ml; MIC, c, and MIC₉₀ of CTM were 0.25 and 0.5μg/ml, respectively. Quinolone resistant E. coli was detected at frequency of 14.0%, which was significantly higher than that in the last year. Almost all drugs showed strong activities against Klebsiella pneumoniae and Proteus mirabilis, and MEPM prevented growth of all strains within 0.125μg/ml. Against Pseudomonas aeruginosa, almost drugs were not so active. The MIC₉₀ of carbapenems and gentamicin (GM) were 16μg/ml and those of all other drugs were more than 32μg/ml. Against Serratia marcescens, the MIC₉₀ of IPM and GM were the lowest value being 2μg/ml, and that of MEPM was 4μg/ml.

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Five-hundred eighty eight bacterial strains isolated from 435 patients diagnosed as having urinary tract infections (UTIs) in 10 institutions in Japan were supplied between August 2000 and July 2001. Then, the clinical background of patients were investigated such as sex, age, and type of infections, infections and kind of bacteria, frequency of bacteria isolation by age and infections, bacteria and infections by timing of antibiotics administration, and bacteria and infections by surgical procedures.
About the relationship between age and sex of patients and type of infections, the number of male patients aged less than 50 years was few, and complicated UTIs without indwelling catheter was the most frequent. In females, the number of patients aged less than 20 years was few. The majority of female patients aged 40 years and over had complicated UTIs while uncomplicated UTIs was most frequent in the patients being twenties. As for type of infections and kind of bacteria, Escherichia coli decreased when the infections became complicated, and Pseudomonas aeruginosa increased when the infection became complicated. Enterococcus faecalis was isolated more frequently in complicated UTIs than in uncomplicated UTIs. Considering this result by age of patients, isolated frequency of E. coil was gradually decreased with aging in patients aged 20 years and over with uncomplicated UTIs or complicated UTIs without indwelling catheter. The isolated frequencies of Klebsiella spp., P. aeruginosa, and E. faecalis were high in the patients with complicated UTIs without indwelling catheter. In the patients aged 70 years and over with complicated UTIs with indwelling catheter, P. aeruginosa and E. faecalis were frequently isolated. As for type of causative organisms in UTIs before and after the administration of antibiotics, the isolation of bacteria was remarkably decreased after administration in the patients with uncomplicated UTIs and complicated UTIs without indwelling catheter. E. coil decreased after administration of antibiotics, and P. aeruginosa increased after administration in the patients with all types of infections. As for type of causative organisms in UTIs and surgical procedures, E. coli was frequently isolated in the patients without surgery in all types of infections, while P. aeruginosa was frequently isolated in the patients who underwent surgery. In uncomplicated UTIs, Proteus spp. and E. faecalis were frequently isolated in the patients with surgery. In complicated UTIs without indwelling catheter, Klebsiella spp. was frequently isolated in the patients without surgery and E. faecalis was frequently isolated in the patients with surgery. In complicated UTIs with indwelling catheter, most of organisms except P. aeruginosa and S. aureus were frequently isolated in the patients without surgery.

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We investigated the in vitro and in vivo antibacterial activities of pazufloxacin mesilate (PZFX mesilate), a new injectable quinolone, and obtained the following results.
1) The MIC₅₀ and MIC₉₀ values of PZFX against clinically isolated Gram-positive and-negative bacteria, ranged from 0.0125 to 12.5 μg/ml and 0.025 to 100μg/ml, respectively. PZFX showed broad spectrum activity. The antibacterial activities of PZFX against quinolone-susceptible, methicillin-resistant Staphylococcus aureus, β-lactamase-negative, ampicillin-resistant Haemophilus influenzae, extended spectrum β-lactamase possessing Klebsiella pneumoniae and imipenem/cilastatine (IPM/CS)-resistant Pseudomonas aeruginosa were superior to those of ceftazidime (CAZ), ceftriaxone, IPM/CS, meropenem and panipenem/betamipron.
2) PZFX showed superior bactericidal activity against S. aureus, Escherichia coli, Proteus mirabilis, Serratia marcescens and P. aeruginosa to hose of CAZ and IPM/CS after treatment for 15 minutes at the drug concentration equivalent to that in human serum at clinical dose to be continued for 15 minutes.
3) CAZ and IPM/CS had no bactericidal activity at the 16 times of MIC against P aeruginosa in human polymorphonuclear leucocytes, while PZFX exhibited potent bactericidal activity ina dose-dependent manner against such bacteria.
4) PZFX inhibited both DNA gyrase and topoisomerase IV from S. aureus at nearly the same level. PZFX showed poor inhibitory activity against topoisomerase II from human placenta and showed high selectivity to bacterial topoisomerase.
5) PZFX mesilate showed superior therapeutic activity to that of CAZ with following infection model caused by S. aureus and P. aeruginosa or each; systemic infection with cyclophosphamide-treated mice, systemic infection in mice with high challenge doses, CMC pouch infection in rat, and calculus infection in rat bladder.
6) Intravenous administration of PZFX with hih plasma concentration just after administration, showed more exellent therapeutic effect against the rat intraperitoneal infection, than p.o. and s. c. administration.

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The in vitro combination effects of pazufloxacin (PZFX) with various antibiotics were investigated by the checkerboard dilution method using piperacillin (PIPC), tazobactam/piperacillin (TAZ/PIPC), ceftazidime (CAZ), cefozoprane (CZOP), imipenem/cilastatin (IPM/CS), meropenem (MEPM), panipenem/betamipron (PAPM/BP), amikacin (AMK) and isepamicin (ISP) for clinical isolates of 27 Pseudomonas aeruginosa strains, vancomycin (VCM), teicoplanin (TEIC) and arbekacin (ABK) for clinical isolates of methicillin-resistant 26 Staphylococcus aureus (MRSA) strains, respectively. The following results were obtained.
1. For 27 P. aeruginosa strains, the synergistic effects were observed with the combination of PZFX and CAZ or MEPM (11.1%: 3 strains), and PZFX and CZOP or PAPM/BP (3.7%: 1 strain), respectively. The additive and synergistic effects of PZFX were observed with the combination in all β-lactams tested in the strains more than 50%. No antagonistic effect was observed. The additive effects were also observed with the combination of PZFX and AMK or ISP in the strains more than 50% of the test strains and no antagonistic effect was observed.
2. For 26 MRSA strains, no antagonistic effect was observed with the combination of all antibiotics tested. The indifference was observed with the combination of PZFX and VCM or ABK in the strains more than 60%, and the additive effects were observed with the combination of TEIC in the strains more than 80%.
In conclusion, no antagonistic effect was observed in PZFX with the combination of β-lactams and anti-MRSA agents, suggesting that the combination therapy of PZFX with these antibiotics would be possible to use for the infections caused by P. aeruginosa and MRSA.

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[in Japanese]

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[in Japanese]

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