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The efficacy and the safety of biapenem (L-627), a new carbapenem antibiotic, against infections in pediatrics were studied. The obtained results are summarized as follows. 1. L-627 at dose levels of 5.4 mg/kg to 12.4 mg/kg (daily doses of 16.2 mg/kg to 37.2 mg/kg) was administered by intravenous drip infusion 3 times daily for 5 to 7 days to 2 cases of pneumonia, 3 cases of skin and soft-tissue infections and 1 case of urinary tract infection for a total of 6 cases. As results, all the cases showed good or better responses including 4 excellent and 2 good results. Bacteriological efficacies in all of the 3 eligible cases were assessed as "eradicated". 2. As for the safety, a decrease in the WBC count and slight elevation of GOT and GPT were observed in 1 case as abnormal changes in the laboratory tests results, only incidence of side effect observed was the eruption in 1 case. 3. The results above indicate that L-627 is useful for the treatment of general infections in pediatrics.

Ceftazidime ( CAZ ), a new injectable cephem antibiotic, was used for treatment of infections in children, and the following results were obtained. After an intravenous injection of CAZ at a dose of 20 mg/kg, the mean blood levels in 2 patients were 41.5 micrograms/ml at 30 minutes, 18.1 micrograms/ml at 2 hours and 2.55 micrograms/ml at 6 hours, with the half-life (T 1/2) of 1.37 hours. In a 22-day-old baby with meningitis given CAZ intravenously at a dose of 43.5 mg/kg, the blood levels were 100 micrograms/ml at 30 minutes, 68 micrograms/ml at 2 hours and 25 micrograms/ml at 6 hours, with the half-life (T 1/2) of 2.96 hours. After intravenous administration of CAZ in doses ranging from 35.7 to 50 mg/kg, CSF concentrations ranged from N.D. to 6.3 micrograms/ml in 3 patients with purulent meningitis, although 19 micrograms/ml at 1 hour and 13 micrograms/ml at 2 hours in 1 patient after intravenous administration of 46.7 mg/kg. In patient with mumps meningitis, CSF concentrations were undetectable after intravenous administration of 35.7 mg/kg. Seventeen patients (each 1 patient with lymphadenitis, tonsillitis and septicemia, each 2 patients with pneumonia, bronchiectatic bronchitis, pyothorax and purulent meningitis, each 3 patients with pyelonephritis and enteritis) were treated with CAZ intravenously, at the daily doses of 178.2 mg/kg and 200 mg/kg in 4 divided doses in patients with meningitis and 44.1 to 103.4 mg/kg in 3 divided doses in patients with other infections (two of them were given by intravenous drip infusion for 30 minutes). The clinical responses were excellent or good in all the patients except for 1 case of Salmonella enteritis (poor) and 1 case of Campylobacter enteritis (poor). The efficacy rate was 88.2%. It was noteworthy that the clinical response was excellent in 1 case of septicemia with P. aeruginosa with leukemic stage of malignant lymphoma and in 2 cases of purulent meningitis. As side effects, fever, eruption, leukocytopenia, elevation in GOT and positive CRP considered to be allergic, were observed on day 16 of administration in 1 case of pyothorax. These symptoms disappeared by discontinuance of administration. In addition, there were elevation in GOT and GPT in 2 cases and elevation in GOT in 2 cases and elevation in GPT in 1 case; they were all mild or transient, and there was nothing to be worried about.(ABSTRACT TRUNCATED AT 400 WORDS)

Ceftriaxone (Ro 13-9904, CTRX), a new parenteral cephalosporin, was used for pediatric infections and the following results were obtained. CTRX was administered twice daily by intravenous injection with about 20 mg/kg in 6 cases consisting of 2 cases with purulent lymphadenitis of the neck, 2 with urinary tract infection, 1 with sepsis and pyelonephritis and 1 with sepsis and purulent lymphadenitis of the neck. The result was excellent in 4 and good in 2. One case with H. influenzae meningitis, receiving 50 mg/kg CTRX by intravenous injection twice daily, showed an excellent response without having any sequela. Among those mentioned above, diarrhea in 2 cases and elevated GOT and GPT in 2 were observed, all of which were transitory and not serious. The blood level of CTRX at 1/2, 1, 2, 4, 6 and 8 hours after intravenous injection with 20 mg/kg to a girl of 8 years and 8 months of age with urinary tract infection was 114, 86, 70, 42, 29 and 21.8 micrograms/ml, respectively. The half-life time was 3.5 hours while the urinary recovery rate up to 6 hours was 58.0%. The concentration in the cerebrospinal fluid of 1 case with H. influenzae meningitis ranged from 2.1 to 8.2 micrograms/ml at 3 hours after administration and from 1.15 to 2.65 micrograms/ml after about 12 hours (prior to the next administration). The above-mentioned results suggest that CTRX is a new antibiotic useful for pediatric infections caused with susceptible bacteria and is effective by intravenous injection with 10 mg/kg twice daily for moderate infections and with 20 mg/kg twice daily for severe ones, except for meningitis. As for purulent meningitis, the administration dosage and frequency will have to be further examined based on the intravenous injection with 50 mg/kg twice daily.

We conducted several studies using a combination of sulbactam (SBT) and cefoperazone (CPZ) in a ratio of 1:1 with the following results. Serum and cerebrospinal fluid (CSF) concentrations of the drugs were determined in 2 rabbits with meningitis caused by S. aureus. Following intravenous injection, serum concentrations of CPZ were higher than those of SBT in both rabbits whereas CSF concentrations were much higher with sulbactam than with CPZ indicating good penetrability of SBT into CSF. The serum concentration of SBT at 1/2, 1, 2 and 4 hours after an intravenous administration of 9.8 mg/kg of the combination to a child were 3.5, 1.4, 0.3 and 0.1 microgram/ml and those of CPZ 19.0, 13.0, 6.7 and 2.9 micrograms/ml, respectively. The half-lives were 0.705 hours for SBT and 1.31 hours for CPZ. An intravenous dose of this combination (19.6 mg/kg) was given 3 times a day to 13-year-old girl with decreased neutrophil chemotaxis due to periblepharal abscess caused by S. aureus. The therapeutic effect was excellent. Though very slight transient eosinophilia was noted, no adverse reaction was found. The susceptibility of the isolated organism to this drug was not determined, but it was found to be resistant to the CTX using the disc method.

Clinical trial of cefotiam was made in children and the following results were obtained. 1. Pharmacodynamic studies of the drug in CSF of experimental staphylococcal meningitis in rabbits showed a CSF/serum ratio of T 1/2 of 3.52, which was relatively high, but a percentage of CSF/serum ratio of AUC of only 3.42% up to 3 hours, suggesting a low efficiency of passage of the drug into CSF. 2. Blood concentrations of the drug were determined in children after an intravenous bolus injection of 20 mg/kg and were 46 mcg/ml (15 min.) and 26 mcg/ml (30 min.), T 1/2 being 40.8 min., Urinary recovery rate was 91.3% up to 4 hours in one patient and 61.9% up to 6 hours in another, respectively. 3. Thirteen patients with the following 14 episodes of infections were treated with cefotiam; urinary tract infection (5 cases), pneumonia (5), empyema (1), tonsillitis (1) and suspected sepsis (2). An overall efficacy rate was 100%, i. e., excellent in 12, good in 2 and no failure. No adverse reactions were clinically discernible and only laboratory abnormalities were transient or slight elevations of transaminase levels in 2 patients. 4. Based on the above results, it was concluded that cefotiam is a potent new antibiotic in the treatment of bacterial infections. Spectrum and antibacterial activity of the drug suggest that the drug particularly indicated for pneumonia.

Ceftazidime (CAZ) was evaluated in the treatment of infections in neonates and premature infants. In 1 mature neonate (age: 14 days) administered with 30.3 mg/kg of CAZ by a single bolus intravenous injection, the serum concentration of CAZ was 50 micrograms/ml at 30 minutes after the dosing, and the elimination half-life was 1.38 hours. The urinary recovery rate of administered CAZ during the first 6 hours was 52.9%. In 6 neonates (mean gestational period: 37.8 weeks, mean birth weight: 2,508 g, mean age: 3.7 days) administered with ca. 20 mg/kg of CAZ by single bolus intravenous injections, the mean serum concentration of CAZ was 63.6 micrograms/ml at 30 minutes after the dosing, and the half-life was 3.78 hours. In 3 out of the above 6 neonates, the mean urinary recovery rate of CAZ during the first 6 hours was 59.8%. Five neonates and 2 infants with infections were given 18.4-65.9 mg/kg of CAZ b.i.d.-q.i.d. by intravenous injections. One of these cases was excluded from an evaluation for clinical efficacy, because CAZ was given only for 2 days. In the remaining 6 cases, clinical efficacy was excellent in 1 case of urinary tract infection (E. coli + E. faecalis), good in 3 cases of pneumonia (P. aeruginosa + K. pneumoniae: 1, P. aeruginosa: 1, and causative organism unknown: 1), and poor in 1 case of sepsis (S. aureus). In 1 case of asphyxia neonatorum contaminated with meconium, CAZ was used prophylactically, resulting with no infection. No clinically adverse effect was observed. Also no abnormality was observed in laboratory analyses in the 6 cases.(ABSTRACT TRUNCATED AT 250 WORDS)