Change in the sensitivity of clinical isolates to cefditoren (CDTR) and oral cephalosporin was investigated by collecting samples in surveys over three successive time periods. In the first survey, 23 species including 805 strains were isolated from clinical materials during the 3-month period from April to June 1995. Twenty-three species 769 strains were collected during the one-year period from July 1996 to June 1997 in the second survey, and 22 species 821 strains from July 1998 to June 1999 in the third survey. The MIC distributions of CDTR and other tested drugs in each test strain that was isolated at the time of the second and third surveys demonstrated tendencies similar to those observed in the test strains isolated for the first survey. The MIC₉₀ values of tested drugs in Streptococcus pneumoniae was higher in the second survey than in the first and third surveys. The antibacterial activity of each drug to Haemophilus influenzae in the third survey was equivalent to those in the first and second surveys. The MIC₉₀ values of CDTR against H. influenzae were superior, 0.025-0.05μg/mL, in the tested drugs in all three surveys, but the MIC₁₀₀ value rose from 0.10μg/mL in the first survey to 0.20μg/mL in the third survey. The susceptibility of various strains against tested antibiotics showed no change across all three surveys. CDTR had tsuperior activity against gram-positive and gram-negative bacteria. In particular, the activity of CDTR against bacteria isolated from respiratory infections was strong and balanced.

View full abstract

The objective of this study was to investigate infections due to carbapenem-resistant Pseudomonas aeruginosa (CRPA) in gastroenterological surgery. We serologically classified 552 strains of P. aeruginosa isolated from clinical specimens between 1983 and 1998. Overall, the rate of CRPA among all P. aeruginosa was 21.6%. The annual isolation rate of CRPA was high (33-47%) in 1990, 1991 and 1994. In the serological study, group F strains (CRPA isolation rate, 90.9%) were prevalent in 1990, and group B strains (CRPA isolation rate, 77.8%) in 1994. By following recommendations for the proper use of carbapenem antibiotics, the CRPA isolation rate maintained at 15.0% between 1995 and 1998.

View full abstract

To evaluate the efficacy, safety, and utility of pazufloxacin mesilate (PZFX, injectable), an injectable new quinolone antibiotic, a phase III clinical study was conducted in patients with burn infections at the Department of Plastic Surgery, Faculty of Medicine, Hokkaido University, and affiliated hospitals (a total of six institutions). Of the total of 10 patients treated with PZFX, one patient was excluded because of violation of the inclusion criteria. Thus, 9 patients were included in the analysis of clinical results and the findings are described below. PZFX was administered in a dose of 300 mg twice a day in 1 case and 500mg twice a day in 8 cases.
1) The clinical results were rated excellent in 5 cases, good in 3 cases, and fair in 1 case, with an efficacy rate including good or better results of 8 9. When classified by daily dose, the efficacy rate was 1 1 for the dosage of 300 mg twice a day and 7 8 for 500mg twice daily.
2) Evaluation of bacteriological efficacy showed an elimination rate of 0 1 for gram-positive organisms and 1 4 for gram-negative organisms in single infections, and 1 1 in polybacterial infections. The overall elimination rate was 2 6. One strain each of Enterococcus faecalis, Enterobacter cloacae, and Acinetobacter calcoaceticus disappeared, and one strain of Staphylococcus aureus (MSSA) and 3 strains of Pseudomonas aeruginosa persisted.
3) No adverse effects occurred in any of the 9 cases included in the analysis. Abnormal laboratory values were observed in 2 of the 9 cases included in the analysis. ALT and Al-P elevations were seen in 1 case and abnormal in urinary protein in 1 case.
PZFX levels in dermal tissue in burns were determined in the Department of Plastic Surgery, Faculty of Medicine, Hokkaido University and affiliated hospitals (a total of 4 institutions), and the results below were obtained. These levels were determined in 5 of the 9 cases included in the analysis of clinical results.
1) PZFX levels in eschar tissues were determined in the 4 cases in which eschar specimens were collected, and the levels were determined to be 1.33 to 7.54μg g (one hour after completion of injection) following administration of a single dose of 500mg.
2) In subeschar tissues, a level of 1.68μEg g was achieved in 1 case given PZFX at 300mg and levels of 2.12 to 8.44μg g in 4 cases given 500mg (one hour after completion of injection).
3) Following administration of a single dose of 500 mg, the mean levels reached were 4.56±2.35μEg g (mean±SD) in the eschar tissues and 4.78±2.60 μg g (mean±SD) in the subeschar tissues, one hour after completion of injection.
4) No adverse effects developed in any of the 5 cases analyzed for safety, and no abnormal laboratory values were observed in any of the 4 cases included in this analysis.
These findings regarding the clinical results and tissue levels achieved in burns indicated that PZFX is a useful drug for the treatment of infections of burns.

View full abstract

Dose-finding studies of a novel new quinolone for injection, pazufloxacin mesilate (PZFX mesilate) were undertaken for bacterial pneumonia. The three-arm comparative trials were conducted in a random manner with ceftazidime (CAZ) as a control agent. The dose regimen of PZFX mesilate (PZFX-600 or PZFX-1000arm) was 600 mg or 1, 000 mg twice a day for 14 days and that of CAZ (CAZ arm) was 2, 000 mg twice a day for 14 days.
1) Subjects for analysis: A total of 120 cases were studied, consisting of 40 patients given PZFX-600, 39 given PZFX-1000, and 41 given CAZ. Among them, 91 cases were selected for analysis of clinical effect (PZFX-600: 33, PZFX-1000: 28, CAZ: 30 cases), 110 cases for analysis of adverse effects (PZFX-600: 37, PZFX-1000: 35, CAZ: 38 cases), 101 cases for abnormal laboratory values (PZFX-600: 35, PZFX-1000: 31, CAZ: 35 cases), and 87 cases for usefulness (PZFX-600: 31, PZFX-1000: 26, CAZ: 30 cases).
2) Clinical effect: Clinical efficacy rates were 100%(33 33) for PZFX-600, 92.9% for PZFX-1000 (26 28), and 93.3%(28 30) for CAZ.
3) Bacteriological effect: Bacteriological eradication rates were 93.3%(14 15) for PZFX-600, 100%(7 7) for PZFX-1000, and 100%(11 11) for CAZ. Streptococcus pneumoniae persisted in one PZFX-600 case.
4) Safety: The occurrence of adverse effects was 0%(0 37) for PZFX-600, 2.9%(1 35) for PZFX-1000, and 2.61%(1 38) for CAZ. None of the events were serious. The rate of laboratory abnormal valuse was 14.3%(5 35) for PZFX-600, 22.6%(7 31) for PZFX-1000, and 31.4%(11 35) for CAZ. Transaminase elevation and eosinophilia were the major incidents, although they were all mild.
5) Usefulness: The usefulness rate was 100%(31 31) for PZFX-600, 92.3%(24 26) for PZFX-1000, and 93.3%(28 30) for CAZ.
There were no statistically significant differences among the three groups in the above studies, including in regrad to clinical efficacy, bacteriological analysis, or safety. Based on the above results, we concluded that the optimal clinical dose for PZFX mesilate is 600 mg or 1, 000mg twice a day for the indication of bacterial pneumonia.

View full abstract

The clinical efficacy, safety, and usefulness of pazufloxacin mesilate, a new quinolone for injection, were evaluated in bacterial pneumonia or lung abscess in a comparative study versus ceftazidime (CAZ). As a rule patients received either 500mg (as pazufloxacin) of pazufloxacin mesilate b. i. d. or 1, 000mg (potency) of CAZ b. i. d., intravenously, for 14 days (28 vials). The following results were obtained in this trial.
1. A total of 232 patients were evaluated in this study, and 185 of them (bacterial pneumonia: 173 cases; lung abscess: 12 cases) were evaluated for clinical efficacy. The cases evaluated for adverse effects, abnormal laboratory findings, overall safety, and usefulness amounted to 225, 208, 210, and 182, respectively.
2. The clinical efficacy rate was 90.7%(78/86) in the pazufloxacin mesilate group and 89.9%(89/99) in the CAZ group. Both groups showed high efficacy. Since the 90% confidence interval of the efficacy rate difference between the two groups was -7.5-9.1%, the clinical equivalency (non-inferiority) of the pazufloxacin mesilate group to the CAZ group was demonstrated at Δ=10%. Although significant bias was found between the two groups in the patient background factors concerning “sex”, “concomitant drugs”, “body temperature”, “ESR”, “CRP”, and “chest X-ray findings”, clinical equivalency of the pazufloxacin mesilate group to the CAZ group was conclued after correction for these biases too.
3. Among the cases evaluated for clinical efficacy, 85 cases in which the causative organisms were isolated were evaluated for bacteriological effects. The bacteriological eradication rate was 81.1%(30/37) in the pazufloxacin mesilate group and 100%(48/48) in the CAZ group, and the difference between the two groups was statistically significant (p=0.002, Fisher's exact probability method).
4. The incidence of adverse effects was 5.5%(6/110) in the pazufloxacin mesilate group and 7.8%(9/115) in the CAZ group, and the difference between the groups was not significant. The incidence of abnormal laboratory findings was 31.0%(31/100) in the pazufloxacin mesilate group and 29.6%(32/108) in the CAZ group, and the difference between the groups was not significant. None of the adverse effects were serious.
5. The safety rate was 65.3%(66/101) in the pazufloxacin mesilate group and 62.4%(68/109) in the CAZ group, and the difference between the groups was not significant.
6. The usefulness rate was 86.6%(71/82) in the pazufloxacin mesilate group and 82.0%(82/100) in the CAZ group, and the difference between the groups was not significant.
These findings indicate that pazufloxacin mesilate is one of the most effective drugs for bacterial pneumonia.

View full abstract

The clinical efficacy, safety and usefulness of pazufloxacin mesilate, a new quinolone for injection, were evaluated in chronic respiratory tract infections in a comparative study versus ceftazidime (CAZ). As a rule, patients received either 500mg (as pazufloxacin) of pazufloxacin mesilate b. i. d. or 1, 000mg (potency) of CAZ b. i. d., intravenously, for 14 days (28 vials). The following results were obtained in this trial.
1. A total of 203 patients were evaluated in this study, and 155 of them, were evaluated for clinical efficacy. Cases evaluated for adverse effects, abnormal laboratory findings, overall safety and usefulness numbered 185, 172, 177 and 153, respectively.
2. The clinical efficacy rate were 93.2%(68/73) in the pazufloxacin mesilate group and 91.5%(75/82) in the CAZ group. Both groups showed high efficacy. Since the 90% confidence interval of the efficacy rate difference between the two groups was-6.6-10.0%, clinical equivalency (non-inferiority) of the pazufloxacin mesilate group to the CAZ group was demonstrated at Δ=10%.
3. Among the cases evaluated for clinical efficacy, the 84 cases in which causative organisms were isolated, were evaluated for bacteriological effects. The bacteriological eradication rate was 65.0%(26/40) in the pazufloxacin mesilate group and 90.2%(37/41) in the CAZ group, and the difference between the groups was statistically significant (p=0.014, x² test).
4. The incidence of side effects was 6.8%(6/88) in the pazufloxacin mesilate and 11.3%(11/97) in the CAZ group, and the difference between the groups was not siginificant. The incidence of abnormal laboratory findings was 14.3%(12/84) in the pazufloxacin mesilate group and 27.3%(24/88) in the CAZ group, and the difference was statistical significant (p=0.041, Fisher's exact probability method). None of the adverse effects were serious.
5. The safety rate was 79.3%(69/87) in the pazufloxacin mesilate group and 64.4%(58/90) in the CAZ group, and the difference was statistically significant (p=0.042, x² test).
6. The usefulness rates were 86.7%(65/75) in the pazufloxacin mesilate group and 80.8%(63/78) in the CAZ group, and the difference between the groups was not significant.
These results indicate that pazufloxacin mesilate is one of the most effective drugs for chronic respiratory tract infections.

View full abstract