Cefozopran (SCE-2787, CZOP) was administered to patients with pediatric infections three to four times daily by intravenous injection or 30-minute intravenous drip infusion, and investigations were made in individual cases, on relationships among doses, pharmacokinetics, effects on pathogenic bacteria and MIC against them, and clinical effects. The following results on optimal doses of CZOP were obtained.
1. Clinical cases in which CZOP was administered at a dose of 10mg (potency)/kg
The subjects were 7 patients including 4 patients with pneumonia. Severities of the diseases were severe in one of the patients with pneumonia, and moderate in the other patients.
The MIC against pathogenic bacteria (4 strains) isolated from these cases ranged from 0.2 to 1.56μg/ml. The serum concentrations were in a range between 1.4 and 7.6μg/ml at 4 hours after administration. In some cases, the serum concentrations were lower than the MICs, though slightly.
In the clinical evaluation, CZOP was excellent in 3 cases, good in 2 cases and fair in 1 case. The evaluation was impossible in 1 case. The efficacy rate was 83.3% (5/6).
In the bacteriological evaluation, 3 out of the 4 strains disappeared. Adverse reactions and abnormal laboratory test values were not observed.
2. Cases in which CZOP was administered at a dose of 20 mg (potency)/kg
The subjects were 5 patients including 2 with pneumonia, and severities were severe in one of the patients with pneumonia, and moderate in the other patients. The MICs against the pathogenic bacteria (3 strains) isolated from these cases ranged from 0.1 to 1.56μg/ml. While, serum concentrations at 4 hours after administration were in a range between 3.0 and 7.7μg/ml sufficiently exceeding the MICs.
In the clinical evaluation, CZOP was excellent in 1 case and good in four cases, with an efficacy rate of 100% (5/5). In the bacteriological evaluation, all the 3 strains disappeared. No adverse reactions were observed, but an abnormal laboratory test value showing eosinophilia was noted in one case.
3. Cases in which CZOP was administered at a dose of 40mg (potency)/kg
The subjects were 5 patients including 3 with pneumonia. The severity was moderate in 2 of the pneumonia patients, and severe in the other three cases. The MICs against the pathogenic bacteria (4 strains) isolated from these cases were in a range between 0.1 and 0.78 μg/ml. The serum concentrations at 4 hours after administration ranged from 6.5 to 21.9μg/ml, sufficiently exceeding the MICs.
In the clinical evaluation, CZOP was excellent in 4 cases and good in 1 case, with an efficacy rate of 100% (5/5). The efficacy rate in the bacteriological evaluation was also 100%. As adverse reaction, red urine was observed in one case. Eosinophilia was noted in one case in the laboratory tests.
When CZOP was administered to patients with pediatric infections at a dose of 10mg (potency)/kg, the clinical effect of the drug was insufficient in a case in which serum concentration of CZOP at 4 hours after administration was lower than the MICs against the pathogenic bacteria. When CZOP was administered at a dose of 20mg (potency)/kg, sufficient concentrations were obtained, and the drug efficacies were found to be excellent or good in all cases. Therefore, the effective dose normally used is considered to be 20mg (potency)/kg. When CZOP was administered at a dose of 40mg (potency)/kg, the drug was found to be excellent or good in all of the cases although the severities were high in more than half of the cases tested. In addition, the rate of excellent efficacies was 80% (4/5). Furthermore, no severe adverse reactions were observed. It was, therefore, confirmed that CZOP should be administered at a dose of 40mg (potency)/kg in severe or intractable cases.

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The following results were obtained in pharmacokinetic, bacteriological and clinical investigations of a cephem antibiotic for injection, cefozopran (SCE-2787, CZOP), administered to neonates and premature infants.
1. Pharmacokinetics
(1) Half-lives (T 1/2's) of CZOP in 0-day-old (less than 24 hours after birth) neonates and premature infants were longer than those in 1-day-old or older infants. When half-lives were compared between 0-day-old neonates and 0-day-old premature infants, longer half-lives were observed in premature infants.
(2) When CZOP was intravenously administered to 1-day-old or older neonates and premature infants at a dose of 20mg/kg, no differences were noted in blood concentrations between neonates and premature infants from 30 minutes to 6 hours after administration as well as T 1/2's.
(3) Blood concentrations of CZOP administered at doses of 10, 20 and 40mg/kg were dose-dependent.
(4) Urine excretion rates of CZOP administered to 1-day-old or older neonates and premature infants were approximately 30 to 60% in the first 6 hours after administration. Urine excretion rates in 0-day-old neonates and premature infants were low.
2. Clinical results
(1) Of a total of 136 cases to which CZOP was administered, clinical efficacy evaluation was possible in 96 cases, and safety evaluation in 132 cases.
(2) The clinical efficacy rates were 78.6% (22/28) in 28 cases in which causative organisms were detected (Group A), and 97.1% (66/68) in 68 cases in which no such organisms were detected (Group B), with the total efficacy rate (Groups A and B) of as high as 91.7% (88/96).
(3) Bacteriological evaluations were made with 33 strains isolated from the 28 cases of Group A. Elimination rates for Gram-positive and Gram-negative bacteria were 88.2% (15/17) and 92.3% (12/13), respectively, with the total elimination rate of 90.0% (27/30). No microbial substitution was noted.
(4) As an adverse reaction, diarrhea was noted in one case (0.8%). Abnormal laboratory test values were noted in 15 cases (12.3%) including eosinophilia, elevated GPT, and elevated γ-GTP. All of these abnormalities were transitory, and none of them critical.
As a result of above pharmacokinetic and clinical investigations, CZOP is considered to be highly useful in the treatment of indicated infections in neonates and premature infants. It appears that 20mg/kg of CZOP can be administered by intravenous injection or intravenous drip infusion to neonates and premature infants aged 0-day (less than 24 hours after birth) once or twice daily, to those aged 1 (24 or more hours after birth) to 7 days twice or three times daily, and to those aged 8 or more days three or four times daily, and that the dose can be increased up to 40mg/kg in cases of critical or intractable infections.

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In order to evaluate antimicrobial activity of cefozopran (CZOP), minimum inhibitory concentrations (MICs) of CZOP and control drugs were determined against Streptococcus pneumoniae from children that were isolated from October of 1995 to January of 1996. Determinations were made for the detection frequency of penicillin-insensitive or resistant strains in biovar utilizing hydrolysis products, and for the correlation of antibacterial susceptibility and macrolides (MLs)-resistant patterns.
The results are summarized as follows;
1. MIC₉₀ of CZOP was ≤0.025μg/ml against benzylpenicillin (PCG)-susceptible S. pneumoniae (PSSP, 50 strains). MIC distribution of CZOP against these strains was approximately equal to that of PCG, and showed stronger activities of CZOP than those of ceftazidime (CAZ), flomoxef (FMOX) and erythromycin (EM).
2. MIC₉₀ of CZOP was 0.39μg/ml against 50 strains of PCG-insensitive S. pneumoniae (PISP) and PCG-resistant S. pneumoniae (PRSP). Antimicrobial activities of CZOP against these strains were stronger than those of CAZ, FMOX, PCG and EM.
3. These isolated strains of PISP and PRSP did not show type III biovar, but showed types I and II. The detection frequency of MLs-constitutive resistant strains were high among type III PSSP and those of MLs-inductive resistant strains were high among types I and II PISP and PRSP.
4. These data suggested that CZOP had strong antimicrobial activities against multiple drug resistant S. pneumoniae including penicillin-resistant strains. CZOP will be effective against S. pneumoniae which often are causative organisms in infections of children.

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We examined the clinical effect of sulbactam/cefoperazone (SBT/CPZ) on respiratory tract infections in elderly patients (from 65 to 91, average 70.8) with underlying respiratory diseases. Thirty (30) patients (25 men and 5 women) were registered and SBT/CPZ (2g/day) divided into two doses, was administered intravenously through drip infusion.
The efficacy rate was 63% (excellent in 1 patient and good in 18 patients). No significant difference in efficacy was found among patient's age groups (group 1: 65-69, group 2: 70-74, group 3: 75-79, group 4:>80). Bacteriological eradication rate was 50% (6 out of 12 strains). An adverse reaction occurred in one patient, who experienced urticaria. Laboratory abnormalities, which were increasing with their ages, were observed in 12 patients during the study.
These results suggest that SBT/CPZ was effective, but we found it is important to use caution in the treatment of elderly patients on respiratory tract infections with underlying respiratory diseases.

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To evaluate antimicrobial activities of tosufloxacin (TFLX), minimum inhibitory concentrations (MICs) of TFLX and other drugs were determined against clinical isolates that were obtained in our laboratory from February of 1993 to January of 1994 (Period I), and from February of 1995 to January of 1996 (Period II).
The results are summarized as follows:
1. Compared to MIC90's reported by others for TFLX in the 1980's, those obtained by us against i3-streptococci, Streptococcus pneumoniae, Peptostreptococcus spp., Haemophilus influenzae and Salmonella spp. were similar to, but those obtained against other bacteria were higher than those reported values.
2. D etection frequencies of resistant strains to TFLX were compared between Period I and Period II. MIC90's of TFLX against Staphylococcus spp., Morganella morganii, Providencia spp., Pseudomonas aeruginosa, ? A-streptococci, S. pneumoniae and Peptostreptococcus spp. were lower in Period II than in Period I, but MIC90's of TFLX against Propionibacterium acnes, Escherichia coli, Klebsiella spp., Proteus spp., Neisseria gonorrhoeae and Bacteroides fragilis group were higher in Period II than in Period I. TFLX-insensitive or -resistant H. influenzae were found among strains isolated in either of the Periods.
3. Most of the TFLX -resistant Gram-negative organisms tested were also resistant to other NQ's.
4. TFLX showed strong antimicrobial activities against penicillin-resistant S. pneumoniae.

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