The in vitro antibacterial activity of cefozopran (CZOP) against recent clinical isolates was evaluated and compared with those of ceftazidime (CAZ), cefpirome (CPR), cefepime (CFPM), cefotaxime (CTX), sulbactam/cefoperazone (S/C), imipenem (IPM), oxacillin (MPIPC), and flomoxef (FMOX). MIC₈₀ values of CZOP for methicillin-susceptible Staphylococcus aureus (MSSA, n=41), methicillin-resistant Staphylococcus aureus (MRSA, n=57), Streptococcus pneumoniae (n=45), Enterococus faecalis (n=49), Enterobacter cloacae (n=50), Citrobacter freundii (n=45), Serratia marcescens (n=45), and Pseudomonas aeruginosa (n=100) were 1, 32, 2, 16, 4, 1, 0.25, 8μg/ml, respectively.
CZOP was more active than CPR against P. aeruginosa and exhibited similar activity to CPR against other species. CZOP was especially active against S. marcescens with MIC values lower than 1μg/ml against all strains tested. CZOP was similarly active to or more active than CFPM against all species except for C. freundii.
CZOP was not active against MRSA. Thus, we investigated the in vitro combination effects of CZOP/vancomycin (VCM) and CZOP/arbekacin (ABK) using the checkerboard method. The interaction between CZOP and VCM ranged from additive activity (0.5 < FIC index ≤ 1.00, n=37) to synergistic activity (FIC index < 0.50, n=1), except for one strain showing indifference (1.00 < FIC index ≤ 2.00). The interaction between CZOP and ABK ranged from additive activity (n=22) to synergistic activity (n=1). These date suggest the potential effect of combination therapy of (CZOP) and VCM or ABK against MRSA. The combined therapy is suggessted to be useful to reduce side effects in patients with impared renal function, to reduce the administration dose of VCM or to treat infections of sites where achievable drug concentrations are lower than those commonly achieved in the bloodstream.
We also investigated the combination effects of CZOP/AMK and CZOP/GM against CZOP-resistant P. aeruginosa (MIC > 16μg/ml). The combination of CZOP/AMK showed additive activity (n=9) to synergistic activity (n=2). The combination of CZOP/GM showed additive activity (n=5). These results suggest that combinations of CZOP with AMK or GM are effective in treating P. aeruginosa.

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We conducted fundamental and clinical evaluations of a cephem antibiotic, cefozopran (SCE-2787, CZOP), in infants with low birth weights and mature infants.
(1) Blood concentrations CZOP was intravenously given in bolus dose of 20mg/kg to the newborn. The blood antibiotic concentrations were 69.7 μg/ml at 30 minutes after administration and the elimination half life was 2.99 hours in mature infants aged 1-3 days. They were 38.7 μg/ml and 2.85 hours in those aged 4-7 days, and 40.8 μg/ml and 3.81 hours in those aged 8 days or elder, respectively. In infants with lower birth weights aged 4-7 days the blood antibiotic concentrations were 48.6 μg/ml at 30 minutes after i. v. administration and the elimination half life was 3.77 hours. The blood antibiotic concentrations at 30 minutes after intravenous doses of 10, 20 and 50 mg/kg in mature infants aged 8 days or elder were 21.1, 40.8 and 153.6 μg/ml (value at 60 minutes) and the elimination half lives were 2.24, 3.81 and 3.07 hours, respectively.
Administration of CZOP at doses of 20 and 40 mg/kg by intravenous drip infusion over 30 minutes gave the blood drug concentrations of 48.0 and 103.2 μg/ml at the end of infusion and the half lives were 2.60 and 3.33 hours, respectively.
(2) Urinary excretion The urinary excretion rates after i. v. bolus doses of 10, 20 and 40 mg/kg were 28.4-58.6% of dose. The urinary excretion rate after i.v. drip infusion of 40 mg/kg over 30 minutes was 49.0% of dose.
(3) Transfer into cereblospinal fluid
The transfer of the antibiotic into cereblospinal fluid in patients with serous meningitis was 4.1-15.5 μg/ml at 1 hour after administration.
(4) Clinical results The clinical efficacy was judged “good” or “excellent” in 2 of the 3 patients with septicemia and in all of the 10 patients with suspected septicemia. It was judged “excellent” in all of the 9 patients with pneumonia, 3 with urinary tract infections and 3 with intrauterine infections. Prophylactic use of the antibiotic was effective in all of the 12 patients. Of the patients in whom bacteriological evaluation was successful, 7 of the 10 causative organisms were confirmed to be eradicated.
No adverse drug reactions of signs and symptoms were recognized. Fourteen abnormal alterations of the laboratory test values such as elevation of γ-GTP and that of GPT were recognized in 8 patients (16.7%). None of them were particularly serious.
These results indicate that CZOP is a drug useful for treatment and prevention of infections in infants with lower birth weights as well as in mature infants.

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Cefozopran (CZOP) was administered to nine newborn patients with infections at a dose of 20 mg/kg twice or three times daily for 5 to 6 days to evaluate the efficacy, safety and pharmacokinetics of cefozopran.
1. Blood concentrations
CZOP was intravenously given to 6 newborn patients by drip infusion at a dose of 20 mg/kg over 30 minutes. The maximum blood concentrations (C_max) were 38.4 μg/ml in a patient aged 0 day, 37.7 and 54.3 μg/ml in two patients aged 1 day, 51.3 and 64.1 μg/ml in two patients aged 3 days and 51.0μg/ml in a patient aged 5 days. C_max. was lower in the patient aged 0 day. The elimination half life (T 1/2) was 9.2 hours in the patient aged 0 day, 4.9 and 3.7 hours in the patients aged 1 day, 3.1 and 2.4 hours in the patients aged 3 days and 2.9 in the patient aged 5 days, showing a prolongation of T 1/2 in patients of lower age.
2. Urinary excretion
Of the 6 patients given CZOP at a dose of 20 mg/kg by intravenous drip infusion over 30 minutes, urine was collected in 5 patients. The cumulative excretion rate within 6 hours after infusion was as low as 19.8% of dose in the patient aged 0 day. The rates were elevated as high as 46.3 and 57.0% of dose in the patients aged 1 day. In the patient aged 3 days, the recovery within 4 hours after infusion was 47.3%. It was 70.6% of dose within 6 hours after dosing in the patient aged 5 days. The urinary recovery within 6 hours after dosing increased with the advance of age.
3. Clinical results
Efficacy was evaluable in 7 patients. Of them, 3 had suspected septicemia, 2 pneumonia, 1 intrauterine infection and 1 urinary tract infection. The clinical efficacy was judged “excellent” in all the evaluable patients. Neither adverse drug reactions of signs and symptoms nor abnormal alterations of the laboratory test values were recognized in the 9 patients evaluable for safety.
These results suggest that CZOP is an effective and safe drug for treatment of infections in the newborns. As for the dosage and method of administration from the view of the pharmacokinetic data obtained, intravenous drip infusion of 20 mg/kg once or twice daily was considered to be sufficient for patients aged 0 day. For patients aged 1 to 7 days and those aged 8 days or elder, the administration of twice to 3 times daily and 3 to 4 times daily were considered to be sufficient, respectively.

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The efficacy, safety and pharmacokinetics of cefozopran (CZOP) were evaluated in neonates and the following results were obtained:
1. Of the 12 patients treated with CZOP, judgment of clinical efficacy was evaluable in 10 patients (including 5 with pneumonia and 3 with urinary tract infections). The treatment was effective and the causative organism was eradicated in 100% of the patients.
2. No adverse signs and symptoms were recognized during the treatment with CZOP. A slight elevation of direct bilirubin was recognized as an abnormal alteration of laboratory test values in one patient. The value, however, returned to the normal range after the completion of treatment.
3. The pharmacokinetic evaluation was made in 3 of the 12 patients. The blood CZOP levels were recognized in proportion with the dosages. The elimination half lives (T 1/2) in those patients were 8.92, 2.90 and 2.76 hours. Prolongation of T 1/2 was recognized in the patient aged 0 day. It was possible to examine the urinary excretion only in one patient aged 18 days. The excretion rate of the drug was 68.6% of dose by 8 hours after administration.
These results suggest that CZOP is a drug useful for treatment of infections in neonates as well, with high efficacy and safety.

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Cefozopran (SCE-2787, CZOP), which is already on the market with a variety of approved indications in infectious diseases for adult patients, was administered to premature and newborn patients to evaluate the pharmacokinetics and the clinical efficacy.
1. Pharmacokinetics
CZOP was intravenously administered at doses of 10.0 mg/kg, 21.4 mg/kg and 40.0 mg/kg to premature and newborn patients, and the blood concentrations and urinary excretion rate were examined.
The blood CZOP concentrations were 31.7 and 65.5 μg/ml at 30 minutes after administration of 10.0 mg/kg and 40.0 mg/kg, respectively. The elimination half life was 1.78 hours and 2.31 hours, and the urinary recovery was 110.7% and 53.7% within 6 hours after administration, respectively. In the patient given 21.4 mg/kg, the blood CZOP concentration was 36.4 mg/kg at 1 an hour after administration and the elimination half life was 3.97 hours. The urinary recovery was 29.6% within 5 hours after administration.
2. Clinical results
The clinical efficacy was evaluated in 19 patients and judged “good” or better in 13 of them with the efficacy rate of 68.4%. The bacteriological response was evaluated in 10 patients from whom Gram-positive cocci of S. aureus (6 strains), S. pneumoniae (1 strain) and E. faecalis (1 strain) and Gram-negative bacilli of H. influenzae (2 strains) and E. coli (2 strains) were isolated as possible causative organisms. With exception of 1 strain each of S. aureus and H. influenzae, which were not tested after the treatment with CZOP, all of these strains were found to be eradicated.
3. Adverse drug reactions (ADRs) of signs and symptoms and abnormal alterations of laboratory test values.
Safety evaluation was made in 24 patients. ADRs of signs and symptoms were recognized in none of them. As abnormal alterations of laboratory test values, increased eosinophils in 3 patients, elevated GOT in one and elevated GPT in one were recognized.
These results indicate that CZOP is a drug useful for treatment of infections in premature and newborn patients.

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Pharmacokinetic and clinical evaluation of an injectable cephem antibiotics, cefozopran (SCE-2787, CZOP), was conducted in newborn patients and the following results were obtained:
1. Clinical results
The clinical efficacy of CZOP was evaluated in one each patient with intrauterine infection and suspected septicemia. The efficacy was“excellent”in both patients. No clinically serious adverse drug reactions of signs and symptoms and abnormal alterations of the laboratory test values were recognized.
2. Pharmacokinetics
CZOP was intravenously given to newborn patients at doses of 25.0, 20.0 and 18.75 mg/kg. The blood CZOP concentrations were 44.7±7.0μg/ml (n=3), 48.3μg/ml and 48.2μg/ml at one hour after administration, respectively. The elimination half life (T 1/2) was 4.22±1.17 hours (n=3) in the patients given 25.0 mg/kg and 2.74 hours in the patient given 20.0 mg/kg.
The urinary drug excretion rate was 44.58.7% and 31.3±9.7% of dose within 8 hours after administration of 25.0 mg/kg and 20.0 mg/kg, respectively.

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