The bacteria (Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Klebsiella spp. and Pseudomonas aeruginosa) isolated from patients diagnosed as urinary tract infections (UTIs) in 13 institutions in Japan were supplied between August 2002 and July 2003. The susceptibilities of these bacteria to various antimicrobial agents were examined. The bacteria were divided into 2 groups consisting of uncomplicated UTIs and complicated UTIs (with and without indwelling catheter) based on their isolation origins. The results were compared with those obtained between 1993 and 2001.
The drug sensitivity of S. aureus in this year was similar to those in up to the previous year and S. aureus showed the best susceptibility to vancomycin. The drug sensitivity of E. faecalis in this year also was similar to those in up to the previous year. The drug sensitivity of E. coli in this year was generally good except penicillins and was similar to those in up to the previous year. Among cephems, cefozopran (CZOP) and cefpirome (CPR) showed the highest potency (MIC₉₀:≤0.125μg/mL). An antibacterial activity of cefotiam (CTM) was similar to it in 10 years ago and was fine (MIC90:≤1μg/mL). The sensitivity of E. coli to carbapenems and carumonam (CRMN) also was good like to CZOP. However, the sensitivity of the complicated UTIs group to quinolones decreased after 2000 and was suggested to develop the resistance to the drug. The drug sensitivity of Klebsiella spp. in this year also was similar to those in up to the previous year. The bacteria showed good susceptibility (MIC:≤0.125μg/mL) to cefmenoxime (CMX), CPR, cefixime (CFIX), flomoxef (FMOX), and CZOP among cephems. The drug sensitivity of P aeruginosa was generally low. Most of the bacteria were little sensitive to cephems except CZOP and ceftazidime (CAZ). The sensitive bacteria to CZOP and ceftazidime (CAZ) were observed to be 26.8% (15/56 strains) and 39.3% (22/56 strains) in complicated UTIs group, respectively. The sensitivity profile of P aeruginosa to the other tested drugs was not much different from that in up to the previous year. However, the sensitivity of the bacteria to carbapenems tended to decrease after 2000, and the low sensitive strains (MIC:≤256μg/mL) were detected at 22.2% (2/9 strains) in the uncomplicated UTIs group and 3.6% (2/56 strains) in the complicated UTIs group.

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The potential for QT interval prolongation of pazufloxacin mesilate (PZFX mesilate), a new quinolone antibacterial agent for intravenous use, was investigated by in vitro and in vivo electrophysiology studies. Following results were obtained.
In vitro electrophysiology study using guinea pig papillary muscles: PZFX mesilate (30-300μm) had no effects on resting membrane potential (RMP), action potential amplitude (APA) and action potential duration (APD). Reference quinolones, sparfloxacin (3-30μM) and moxifloxacin (10-100μm), had no effects on RMP and APA, but significantly prolonged APD at more than 3 and 10 μM, respectively, while ciprofloxacin 10-100μm) had no effect on each parameter.
In vivo electrophysiology study using anesthetized dogs: PZFX mesilate had no effects on electrocardiograph parameter (PR interval, QRS interval, QT interval and QTc) after intravenous administration of 3-30 mg/kg.
These results suggest that PZFX mesilate has low potential for QT interval prolongation.

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We developed a new software named TEICTDM based on the Bayesian estimation utilized in the therapeutic drug monitoring (TDM) of teicoplanin, a glycopeptide antibiotic, for the estimation of individual pharmacokinetic parameters. Therefore, it is necessary to input more than one plasma concentration (s) determined in individual patient. Individual pharmacokinetic parameters were calculated by a leas squares methods, MULTI2 (BAYES). Two-compartment model was applied to determine individual pharmacokinetic parameters in male healthy volunteers in Japan, and the relationship between clearance of teicoplanin and creatinine clearance in adult patients with various degrees of renal impairment in Europe was used. A series of work from data input to graph drawing or printing of results could efficiently carried out with the best of use of this software, suggesting that this software is now available in clinical practice.

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[in Japanese]

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