[Pharmacokinetic and clinical studies with imipenem/cilastatin sodium in neonates].

Pharmacokinetic and clinical evaluations of imipenem/cilastatin sodium (IPM/CS) were carried out in neonates. The following results were obtained: 1. The plasma concentrations of IPM/CS were determined upon doses of 10 mg/10 mg/kg and 20 mg/20 mg/kg administered using 30- and 60-minute drip infusion, respectively. Peak concentrations of IPM/CS were 19.0-34.7 micrograms/ml/32.6-73.4 micrograms/ml, respectively, at the end of the drip infusion. Plasma half-lives of IPM and CS were 1.4-1.6 hours and 1.7-2.1 hours, respectively. 2. Over a period of 6-8.5 hours, urinary excretions of IPM and CS totaled 19.8-42.7% and 46.9-89.3% of the dose administered, respectively. 3. Clinical responses to IPM/CS were excellent in 4 patients, good in 8 patients and unknown in 1 patient. 4. No side effect was observed except for a platelet increase in 2 patients. From the above results, it has been concluded that IPM/CS is an effective and safe drug in the treatment of neonatal infections.

[Bacteriological, pharmacokinetic and clinical studies of a rokitamycin syrup in pediatrics].

Rokitamycin (RKM) dry syrup was administered to a group of pediatric patients. The results obtained are summarized as follows. 1. Of the recent isolates of Streptococcus pyogenes, fewer strains were highly resistant to RKM than to josamycin (JM), midecamycin (MDM), erythromycin and lincomycin. Also, macrolides (MLs)-resistant strains proved to be susceptible to RKM. 2. Recent isolates of Staphylococcus aureus, Streptococcus agalactiae, group G Streptococci, S. pyogenes, Streptococcus pneumoniae and Haemophilus influenzae were more susceptible to RKM than to midecamycin acetate and JM. Oral administrations of 10-15 mg/kg of the drug were followed by its peak concentrations of 0.07-0.77 micrograms/ml in the blood at 30 minutes in many patients, and by an undetectable level at 6 hours also in many of them. T1/2 values were 1.2-2.6 hours, and first 6-hour urinary excretion rates were 1.26-1.74%. 3. Fifty-two patients with acute upper and lower respiratory tract infections, Campylobacter enteritis, etc. were treated with RKM at about 20-40 mg/kg daily for 4-14 days, with an overall efficacy rate of 88.5%. 4. An eradication rate of 81.4% was achieved for 43 strains of 7 species isolated from the patients. 5. No abnormal laboratory test values were observed after treatment with drug 4 approximately 14 days. A side effect, stomach discomfort, was observed in 1 patient.

[Evaluation of cefuzonam in the pediatric field].

Cefuzonam (L-105, CZON) was studied in pediatric infections. A summary of the results it as follows: For recently isolated Staphylococcus aureus strains, Peak MICs of CZON were distributed between 0.39 and 0.78 micrograms/ml showing a greater susceptibility of S. aureus to CZON than to cefoperazone (CPZ), latamoxef (LMOX), and cefmenoxime (CMX). Peak MICs of CZON for Escherichia coli were 0.10-0.20 micrograms/ml, similar to those of CPZ, LMOX, and CMX. Ampicillin (ABPC)-resistant strains were also susceptible to CZON. MICs for Salmonella were similar to those for E. coli. Peak MICs of CZON for Vibrio parahaemolyticus were 0.20-0.39 micrograms/ml. The susceptibility of the bacteria to CZON was far greater than to ABPC, and was similar to CPZ, LMOX, and CMX. With 20 mg/kg drip infusion, serum concentrations reached their peaks at the end of administration with values of 20.6-68.7 micrograms/ml, which decreased to 0.43-1.70 micrograms/ml after 2 hours. Half-lives of CZON in serum were 0.68-1.2 hours. With 50 mg/kg drip infusion, serum concentrations reached their peaks at the end of administration with levels of 69.0-82.0 micrograms/ml, and at after 2 hours 1.85-3.45 micrograms/ml. Thus, an apparent dose response was observed. Half-lives of CZON in serum were 0.63-0.99 hours. Urinary recovery rates in 6 hours were 39.9-80.5%. A total of 44 cases of 10 different types of acute pediatric infections was treated by CZON intravenous drip infusion as the main therapeutic procedure. The efficacy rate was 93.2%, and the compound was effective on purulent infections, acute urinary tract infection, etc. with pathogens such as ABPC-resistant S. aureus, E. coli, and Enterococcus faecalis. Dosage levels per day were 50 to 80 mg/kg in most cases. In infections with S. aureus (8 strains), Streptococcus pneumoniae (3 strains), E. faecalis (1 strain), Haemophilus parahaemolyticus (1 strain), Haemophilus parainfluenzae (2 strains), Haemophilus influenzae (11 strains), Bordetella pertussis (1 strain), E. coli (3 strains), a total of 30 strains, bacterial elimination was noted with an exception of 1 strain of S. aureus. The compound was used for 4 to 15 days, but side effects observed clinically were only 1 case of diarrhea and 1 case of thrombocytosis.

[Fundamental and clinical evaluations of ceftazidime in neonates].

Ceftazidime (CAZ) intravenous injection was evaluated from fundamental and clinical aspects in neonates, and the results obtained are summarized below. Following a 60-minute intravenous drip infusion of CAZ at 10 mg/kg, the peak serum level was 19.8 micrograms/ml at 30 minutes after the completion of the infusion(half-life: 2.75 hours). Following 30 to 60-minute intravenous drip infusions of CAZ at 20 mg/kg, the mean peak serum levels of CAZ were 33.1-33.0 micrograms/ml. Mean levels at 6 hours were 5.2-6.7 micrograms/ml (half-life: 1.6-4.1 hours). Following 30 to 60-minute intravenous drip infusions of CAZ at 25-30 mg/kg, peak serum levels were 51.7-64.6 micrograms/ml (half-life: 1.6-2.05 hours). Dose response relationship was clearly observed in peak serum levels after intravenous drip infusion, and half-lives of serum CAZ levels in neonates aged 0-10 days tended to be longer than those in infants. Following intravenous administration of CAZ at 20-30 mg/kg, urinary excretion rates during the first 6 hours were 18.7-66.5%, and the rates were low in neonates compared to those in infants and children. Following a 60-minute intravenous drip infusion of CAZ at 28.7 mg/kg, the cerebrospinal fluid level was 5.0 micrograms/ml at 3 hours, the ratio of cerebrospinal fluid level to serum level was 22.5%. Eleven neonates were subjected to the present study. Clinical efficacy of CAZ was excellent in sepsis caused by A. anitratus, which showed higher sensitivity to CAZ compared with other cephem antibiotics of the third generation. In all of the other cases, including those of pertussis and acute urinary tract infections and in the prophylaxis of amniotic infection, clinical efficacy of CAZ was excellent or good. S. epidermidis, E. coli and A. anitratus, identified from cultures of pharynx, urine or blood, were rapidly eliminated during the CAZ treatment. Doses of CAZ used in the present study were 29-133 mg/kg/day, mostly in the range of 40-60 mg/kg/day. Durations of treatment ranged from 3 to 10 days. Neither systemic nor local adverse effect was observed, nor was any abnormality observed in laboratory findings.

[Fundamental and clinical studies with imipenem/cilastatin sodium, a new carbapenem antibiotic, in the field of pediatrics].

Fundamental and clinical evaluations of imipenem/cilastatin sodium (MK-0787/MK-0791) were carried out in pediatric patients. The following results were obtained: After intravenous drip infusion of single doses of 10 mg/10 mg/kg to 20 mg/20 mg/kg of MK-0787/MK-0791 in children, peak plasma levels of MK-0787 ranged from 32.0 to 82.0 micrograms/ml at the end of the infusion. The half-life was 49.9 to 64.0 minutes. The cumulative urinary recovery at 6 to 7 hours after the 1 hour drip infusion ranged from 65.5 to 88.9%. Fecal levels of MK-0787 were 4.2 and 23.1 micrograms/g at 6 hours after a 30-minute intravenous drip infusion of 200 mg/200 mg of MK-0787/MK-0791. MK-0787/MK-0791 was administered by intravenous drip infusion to patients with purulent meningitis. Penetration into the cerebrospinal fluid was satisfactory, as were the clinical responses. MK-0787/MK-0791 was administered clinically in doses of 30 mg/30 mg/kg/day to 200 mg/200 mg/kg/day by intravenous drip infusion 3 or 4 times a day for 3 to 22 days to 26 patients with acute pediatric infections. The clinical response was excellent in 18 patients and good in 8 patients. Eradication occurred with 16 isolates; only two strains of Salmonella-B were not eradicated. Anorexia in 1 patient was the only clinical adverse effect reported, and the only adverse effects found in laboratory tests were eosinophilia and thrombocytosis in 1 patient, respectively, and elevation of the S-GOT and S-GPT in 1 patient.

[Clinical studies of cefixime granules in pediatrics].

A newly developed cephalosporin, cefixime (CFIX), was evaluated clinically in 35 pediatric patients. A pharmacokinetic study was also performed with 11 patients. CFIX was administered as granules. The pharmacokinetic study was conducted in 11 patients, each of 6 patients was given CFIX at a dose of 3 mg/kg and each of the remaining patients was given CFIX at 6 mg/kg. Serum concentrations of CFIX were measured at 2, 4, 6, 8 and 12 hours after dosing. Urinary concentrations of CFIX were measured for periods of 0-6 and 6-12 hours after dosing. CFIX was assayed by the disk method using E. coli ATCC 39188 as the test organism. The clinical evaluation was conducted in 35 children including 5 patients of acute tonsillitis, 10 of acute lacunar tonsillitis, 1 of purulent lymphadenitis, 1 of scarlet fever, 8 of acute bronchitis, 5 of pneumonia, 3 of urinary tract infections and 1 of paratyphoid B. One additional patient was included only in the evaluation of safety since he was suffering from Mycoplasma pneumonia. the patients were from 4 months to 8 years 2 months old and 11 of them were inpatients. Daily doses were from 6.0 to 13.5 mg/kg. After CFIX administration in doses of 3 mg/kg and 6 mg/kg, peak serum concentrations were 1.75 and 3.36 micrograms/ml, half-lives were 2.65 and 2.86 hours and urinary excretions rates up to 12 hours after dosing were 16.1 and 12.4%, respectively. Serum concentrations were dose dependent and the half-life was fairly long compared with other known oral cephalosporins. Clinical efficacies of CFIX in 34 patients were "excellent" in 25 children, "good" in 8 and "poor" in 1 with effectiveness rate of 97.1%. Twenty-two strains of causative organisms, including 6 strains of S. aureus, 3 of S. pyogenes, 2 of S. pneumoniae, 3 of E. coli, 5 of H. influenzae, 2 of H. parainfluenzae and 1 of S. paratyphi B, were isolated. After treatment all strains except 2 strains of S. aureus (one was unknown and the other was decreased), 1 strain of S. pneumoniae (unknown) and 1 strain of H. influenzae (unknown) were successfully eradicated but S. paratyphi B was proved again in feces 9 days after treatment. No adverse reaction was observed. Among 18 children who went through laboratory test, however, an elevation of eosinophile and elevations of GOT and GPT were observed in 2 children and 1 child, respectively.

[Fundamental and clinical studies of aztreonam in the field of pediatric].

The fundamental and clinical studies of aztreonam (AZT) were performed. The results were as follows: The MICs of AZT for E. coli and Salmonella sp. which were recently isolated in the pediatric field were less than 0.78 micrograms/ml. AZT also was effective against ABPC/PIPC-resistant bacteria. The MIC of AZT for V. parahaemolyticus was less than 1.56 micrograms/ml. The peak serum levels of AZT which were occurred just after the 1 hour drip infusion of 10-30 mg/kg were 60.5-136.8 micrograms/ml, and at 6 hours after infusion the serum levels were 1.3-6.1 micrograms/ml; therefore, the dose response was proved. The mean half-lives (T 1/2) were between 1.21 and 1.36 hours. The excretion rates in urine up to 6 hours after intravenous drip infusion were between 32.7 and 77.5%. The ratio of the cerebrospinal fluid concentration to serum in the child with purulent meningitis was 3.5% at 1 hour after the intravenous injection at the dose of 69 mg/kg, and the ratios of the subdural fluid levels to serum were 31.3-37.5%. The levels of AZT into the feces by the multiple dosage were 0-840 micrograms/g. Twenty-five pediatric patients with acute infections had been treated by intravenous injection or drip infusion at the doses of 49-120 mg/kg/day (almost 50-100 mg/kg/day) for 4 to 13 days. The efficacy rate of excellent + good was 84% and that of excellent + good + fair was 96%. The efficacy rate of excellent + good was 100% in all cases with upper/lower respiratory tract infection, bronchopneumonia, and acute urinary tract infection caused by Gram-negative rods. The clinical efficacy was observed in all cases with acute bacterial enteritis. Although AZT was clinically effective against Salmonella enteritis, bacteriological efficacy on the causative organisms was not observed in some cases. Although AZT was bacteriologically effective in 1 patient with typhoid, it did not alleviated fever. AZT showed activity to 9 strains isolated from the culture of throat swab, urine and feces. No side effects were clinically observed in all cases, while slight elevations of laboratory findings were observed in 4 cases.

[Clinical studies on SM-4300, a new human gammaglobulin preparation for intravenous use in pediatrics].

Six cases of severe infections in pediatrics, which showed no or insufficient responses to treatment with antibiotics, were treated with additional intravenous infusion of SM-4300. Results were as follows. Three cases of bacterial infections with high fever, showing no response to chemotherapy, were treated with SM-4300, (68-135 mg/kg). Administration of SM-4300 resulted in defervescence, decreasing pain and swelling and showing a trend for improvement in CRP values. Administrations of SM-4300 (61-100 mg/kg) against pleurisy caused by Mycoplasma were effective in defervescence and improvement in chest findings. Clinical effects of SM-4300 were excellent in 2 cases, good in 3 and fair in 1. In this study, no clinical side reactions nor abnormal laboratory values in blood, liver or renal functions were observed.