Laboratory and clinical studies of T-1982 (cefbuperazone in pediatric field

The authors have carried out the laboratory and clinical studies of T-1982 (cefbuperazone). The results were as follows: The sensitivity was estimated by the plate dilution method on 28 strains of S. aureus 26 strains of E. coli, 27 strains of K. pneumoniae, 25 strains of S. marcescens and 14 strains of Proteus sp. isolated from patients. The distribution of susceptibility of S. aureus was 1.25-25 micrograms/ml and the peak of distribution was 12.5 micrograms/ml. The strains of 84.6% of E. coli were inhibited at concentration of less than 0.39 micrograms/ml. The strains of 77.8% of K. pneumoniae were inhibited at concentration of less than 0.2 microgram/ml. The strains of 96% of S. marcescens was inhibited at concentration of less than 3.13 micrograms/ml. The distribution of susceptibility of Proteus sp. was 0.39-25 micrograms/ml. T-1982 was given to intravenous administration for 5 minutes and drip infusion for 30 minutes a single dose of 20 mg/kg of T-1982 to 2 and 2 children respectively. After intravenous administration of T-1982, the mean serum level was peak 88.4 +/- 8.7 micrograms/ml at 15 minutes, 52.5 +/- 2.7 micrograms/ml at 1 hour, 4.6 +/- 0.15 micrograms/ml at 6 hours respectively. Half-life was 89 minutes. And after drip infusion of T-1982, the mean serum level was 75.5 +/- 3.5 micrograms/ml at 30 minutes and 3.1 +/- 0.6 micrograms/ml at 6.5 hours respectively. Half-life was 82 minutes. The mean urinary excretion rate was 94.7%, 57.4 +/- 11.0% up to 6 hours after intravenous administration and drip infusion respectively. T-1982 was effective in 13 cases out of 13 cases with bacterial infections. No side effects were observed except for 1 case with elevation of serum GOT, 1 case with elevation of serum GPT and 2 cases with eosinophilia.     

Fundamental and clinical studies on T-1982 (cefbuperzone), a new cephamycin antibiotic, in the field of pediatrics

Studies on T-1982 (cefbuperazone), a new cephamycin antibiotic, were carried out in the field of pediatrics, and the following results were obtained. 1. Peak MIC of T-1982 against S. pyogenes (group A) lately isolated was 0.39 micrograms/ml, and the drug was active even against highly resistant strains of macrolides, lincomycin, tetracycline and chloramphenicol. 2. Peak MICs of T-1982 were 0.78 microgram/ml against B. pertussis, 0.2 microgram/ml against E. coli and less than or equal to 0.05 microgram/ml against K. oxytoca, and the drug was also active against ampicillin-resistant bacteria. 3. Serum levels and urinary excretions of T-1982 were investigated in 6 cases. When given at a dose of 20-28 mg/kg by 1 hour intravenous drip infusion, serum concentrations of T-1982 attained the peak level of 63.5-75.9 micrograms/ml at the end of administration and sustained the level of 0.9-2.6 micrograms/ml at 6 hours, the serum half-life (T 1/2) ranging 70-82 minutes. Approximately 20-72% of the dose were excreted in the active form into urine within 6 hours. 4. Twenty-seven cases of acute pediatric infections were treated with T-1982 mainly by intravenous drip infusion, and satisfactory clinical results were obtained in all the cases of angina lacunaris, bronchitis, bronchopneumonia, pertussis, sepsis caused by Serratia and acute urinary tract infections caused by ampicillin-resistant E. coli. The efficacy rate was 96.3%. In this study the drug was administered chiefly at a daily dose of 50-70 mg/kg 2-3 times a day for 2-12 days. 5. Gram-positive cocci (S. aureus, S. pneumoniae, S. pyogenes) and Gram-negative rods (H. influenzae, H. parainfluenzae P. vulgaris, B. pertussis, S. marcescens, E. coli) were eradicated by the treatment with T-1982. 6. No noticeable side effects were observed, except for temporary increase of eosinophil in 2 cases and slight elevation of GOT in 1 case.     

Clinical evaluation of ceftriaxone in the pediatric field

Ceftriaxone (Ro 13-9904, CTRX), developed by F. Hoffmann-La Roche Ltd. in Switzerland, was used for the pediatric infections and the following results were obtained. The mean blood level of CTRX in 2 children after a 60-minute intravenous drip infusion with 20 mg/kg was 58.6 micrograms/ml at 30 minutes, 75.0 micrograms/ml at 1 hour, 39.85 micrograms/ml at 2 hours, 27.74 micrograms/ml at 4 hours, 20.71 micrograms/ml at 6 hours, 11.72 micrograms/ml at 12 hours and 3.91 micrograms/ml at 24 hours while the half-life time was 5.9 hours in one child and 7.6 hours in the other. CTRX was used in 22 children with acute infections consisting of 3 with acute pharyngeal tonsillitis, 4 with acute bronchitis, 8 with bronchopneumonia, 6 with infections of skin soft tissue and 1 with salmonellosis. The results were excellent in 5 cases and good in 17, indicating an efficacy rate of 100%. Out of 10 cases where the causative strains were detected, 4 cases were followed about the activities of the respective bacteria, i.e., H. influenzae, Streptococcus group A, S. aureus and Salmonella group B, all of which were eradicated after the end of administration. The daily dose of CTRX ranged from 30 to 50 mg/kg and generally a larger dose was used for serious infections. CTRX was administered twice daily in 20 out of 22 cases, by an intravenous injection in 4 and an intravenous drip infusion in 18, for 2 to 4 days in 16 and 5 to 8 1/2 days in 6. No clinical adverse reactions were observed while the laboratory test found a slight elevation of GOT in one and that of GOT and GPT in another. From the above results, CTRX was judged to be a highly useful drug for treatment of pediatric infections.     

Laboratory and clinical studies on cefamandole in pediatric field (author's transl)

Laboratory and clinical studies were performed on a new semisynthetic cephalosporin, cefamandole (CMD), and following results were obtained. (1) Serum concentrations and urinary recovery rates of CMD were determined after an intravenous administration of CMD 30 mg/kg in 13 children with normal renal function. In 5 of 13 children, mean serum levels after a one shot intravenous injection were 112.5 micrograms/ml at 15 minutes, 52.2 micrograms/ml at 30 minutes, 23.3 micrograms/ml at 1 hour, 4.9 micrograms/ml at 2 hours and trace at 4 hours. In other 5 children, mean serum levels after drip infusion for 1 hour were 78 micrograms/ml at 30 minutes, 59 micrograms/ml at 1 hour, 9.8 micrograms/ml at 2 hours and trace at 4 hours, after the onset of drip infusion. In the remaining 3 children who received CMD by drip infusion for 2 hours, mean serum levels were 24.3 micrograms/ml at 30 minutes, 35.3 micrograms/ml at 1 hour, 30.2 micrograms/ml at 2 hours, 5.3 micrograms/ml at 3 hours and 1.5 micrograms/ml at 4 hours after the onset of drip infusion. Urinary recovery rates in 5 children were 154.7%, 98.3%, 93.2%, 111.8% and 66.9%, respectively, during 8 hours. (2) CMD was administered to 40 patients with various infections (acute U.T.I. 8, acute angina lacunaris; 2, acute bronchitis; 5, cervical purulent lymphadenitis; 2, post-measles bronchopneumonia; 3, acute bronchopneumonia; 18, pyothorax; 2, S.S.S. syndrome; 1) by one-shot intravenous injection at a dose of 40-120 mg/kg per day. The clinical efficacy rate was 92.5% and bacteriological efficacy rate was 79.2%. (3) As the side effect of CMD, eosinophilia was observed in 1 case, rash and elevation of GOT and GPT in 1 case, and proteinuria in 1 case.     

Laboratory and clinical studies of T-1982 (cefbuperazone) in pediatric infectious diseases

Laboratory and clinical studies were carried out with T-1982 (cefbuperazone) in pediatric infectious diseases. Results were as follows. 1. The average serum concentrations of T-1982 following intravenous injection of 10 mg/kg and 20 mg/kg were 35.3, 64.7 micrograms/ml at 30 minutes, 25.5, 41.5 micrograms/ml at 1 hour, 12.4, 21.8 micrograms/ml at 2 hours, respectively. Dose-response was observed. Urinary recovery rates of T-1982 during 6 hours after injection of 10 mg/kg and 20 mg/kg were 57.3% and 73.6%, respectively. 2. The antibacterial activity of T-1982 against clinically isolated organisms was determined. T-1982 was more active than cefazolin and cefmetazole against K. pneumoniae, H. influenzae and E. coli. It was also effective against ampicillin-resistant E. coli. 3. Thirty-seven patients received daily 30-69 mg/kg of T-1982 t.i.d. for 5-9 days. The rate of satisfactory clinical response was 91.9%. 4. Side effects were diarrhea in 4 cases, diarrhea and rash in 1 case and slight elevation of GOT and GPT in 1 case. But these were transient and mild.     

Pharmacokinetic and clinical studies of cefuzonam in pediatrics

Pharmacokinetic and clinical studies were conducted to evaluate cefuzonam (L-105, CZON), a new cephem type antibiotic, in the pediatric field. A total of 9 pediatric patients (2-14 years) was treated with intravenous injection of CZON: 4 cases with one shot of 20 mg/kg, 2 cases with one shot of 40 mg/kg and 3 cases with drip infusion over 1 hour of 40 mg/kg. CZON concentrations in serum and the excretion in urine were determined. Mean serum concentrations of CZON after one shot intravenous injection of 20 mg/kg were 49.0, 22.7, 9.03, 2.13, 0.37, and 0.09 micrograms/ml at 15, 30 minutes, 1, 2, 4 and 6 hours, respectively. With 40 mg/kg one shot intravenous injections, mean serum concentrations were 117.5, 68.0, 26.2, 8.80, 0.63 and 0.19 micrograms/ml at 15, 30 minutes, 1, 2, 4 and 6 hours, respectively. With 40 mg/kg intravenous drip infusions over 1 hour, mean concentrations were 57.1, 78.8, 12.9, 1.12 and 0.23 micrograms/ml at 30 minutes, 1, 2, 4 and 6 hours, respectively. Mean half-lives were 0.69 hour for 20 mg/kg one shot injections, 0.44 hour for 40 mg/kg one shot injections, and 0.58 hour for 40 mg/kg 1 hour drip infusions. Urinary recovery rates in 6 hour after administration were 70.8% (mean) for the 20 mg/kg one shot injection, 44.1% (1 case) for the 40 mg/kg one shot injection, and 60.0% (mean) for the 40 mg/kg 1 hour drip infusion. CZON was administered in 26 cases of pediatric infections, and the clinical efficacy, antibacterial activity, and side effects were evaluated. Of the 26 cases 2 were excluded for the reason of not having bacterial infection, and the remaining 24 cases were assessed. Included in the 24 cases were 16 cases of acute pneumonia, 2 cases of acute purulent lymphadenitis, and 1 case each of acute bronchitis, acute purulent otitis media, acute apical periodontitis, staphylococcal scalded skin syndrome (SSSS), acute pyelonephritis, and acute enteritis. Clinical efficacy evaluation showed 19 excellent cases and 5 good cases, with an efficacy rate of 100%. Bacteriologically, Staphylococcus aureus 1 strain, Streptococcus pneumoniae 1 strain, beta-Streptococcus 1 strain, Haemophilus influenzae 10 strains, Haemophilus parainfluenzae 1 strain, Proteus mirabilis 1 strain, and Campylobacter jejuni 1 strain were determined or assumed as pathogens, but all of them were eradicated.(ABSTRACT TRUNCATED AT 400 WORDS)     

Clinical study in cefuroxime in pediatric field (author's transl)

Cefuroxime (CXM), a new cephalosporin antibiotic, was used in pediatric field, and the following results were obtained. 1. Absorption and excretion CXM was administered by intravenous drip infusion to 3 patients aged 14 years, 1 year and 1 month, and 5 years and 3 months, respectively, at doses of 15.4 mg/kg, 14.1 mg/kg, and 13.2 mg/kg. The following blood levels were obtained; 71 micrograms/ml at the completion of infusion, 26.8 micrograms/ml at 30 minutes, 13.2 micrograms/ml at 1 hours, 5.05 micrograms/ml at 2 hours, 2.07 micrograms/ml at 4 hours, and less than 0.45 micrograms/ml at 6 hours after the infusion. Urinary excretion of the drug administered was measured in one of these cases. The urinary excretion rate at 1 approximately 6 hours after intravenous drip infusion was 50.4%. 2. Clinical result CXM 17 approximately 55 mg/kg were administered for 2 approximately 4 days to 6 patients with acute respiratory tract infection, 1 with acute cervical lymphadenitis, and 1 with acute enteritis. The clinical results was poor in the case with acute enteritis and good in the other 7 cases. No side effect was observed in 9 cases (the above 8 cases plus 1 unassessable case), and the laboratory examination results showed no abnormality, either.     

Fundamental and clinical evaluation on ceftriaxone in the pediatric field

Fundamental and clinical evaluation on ceftriaxone (Ro 13-9904, CTRX) was performed. CTRX was compared with CEZ, CMZ, CTX and LMOX in the antibacterial activity against the clinical isolates such as S. aureus, E. coli, P. mirabilis, K. pneumoniae and S. marcescens. Against S. aureus, the MIC of CTRX ranged from 0.2 to greater than 100 micrograms/ml with a peak of 3.13 micrograms/ml, showing that CTRX was almost equal to CTX in activity, slightly superior to LMOX and much inferior to CMZ and CEZ, although some strains were not susceptible to CEZ. Against the intestinal strains of E. coli, K. pneumoniae and P. mirabilis, the MIC distribution of CTRX was similar to that of CTX and LMOX while CTRX showed the MIC as high as 3.13 micrograms/ml or above against 44% of all strains including the beta-lactamase producing strains of E. coli and K. pneumoniae, indicating a slight tendency of their becoming resistant. The MIC peaks against E. coli, K. pneumoniae and P. mirabilis were less than or equal to 0.1, 0.39 and less than or equal to 0.1 microgram/ml, respectively. As to S. marcescens which is drawing attention as a causative agent for infections inside of hospitals or those among young infants, CTRX inhibited 84% of the strains at 3.13 micrograms/ml, showing a definite superiority to CEZ and CMZ and a slight superiority to CTX and LMOX. The serum concentration after a single intravenous injection with 40 mg/kg reached a mean peak of 168.8 micrograms/ml at the first blood sampling (at 30 minutes) and gradually decreased to 137.5 micrograms/ml at 1 hour, 30.9 micrograms/ml at 6 hours, 12.6 micrograms/ml at 12 hours and 3.8 micrograms/ml at 24 hours, while the half-life time was 6.0 hours. The comparison of the serum level by 1 hour intravenous drip infusion between the dosage groups of 20 mg/kg and 40 mg/kg revealed that the former group reached a peak of 85.4 micrograms/ml at the termination of drip while the latter's peak was 176.6 micrograms/ml observed during the drip (30 minutes after the initiation of drip). The respective levels of the 2 groups were 15.4 and 32.1 micrograms/ml at 6 hours, 5.1 and 15.0 micrograms/ml at 12 hours, and 1.6 and 4.1 micrograms/ml at 24 hours, indicating a distinct dose-response 2 hours after the initiation of drip administration. The half-life times were 4.9 and 6.2 hours, respectively, which are the longest among the cephalosporins presently being developed.(ABSTRACT TRUNCATED AT 400 WORDS)     

Evaluation of cefpiramide, a new cephem parenteral preparation developed in Japan, in pediatrics

Fundamental and clinical studies of cefpiramide (CPM), a newly developed cephem antibiotic with a broad spectrum, were performed and the following results were obtained. The serum levels of CPM after the intravenous injection or the drip infusion of CPM at dose of 10.0 approximately 46.7 mg/kg reached the peak of 75.8 approximately 274.0 micrograms/ml at 30 approximately 60 minutes after infusion and were 3.9 approximately 55.1 micrograms/ml at 8 hours after the infusion. Half-life of CPM in the blood was between 2.4 and 7.0 hours. The excretion rates of CPM into urine up to 24 hours after the infusion were 5.7 approximately 20.4%. Twenty-five patients with acute respiratory tract infection (RTI, 15 cases), urinary tract infection (UTI, 8 cases), cellulitis (1 case) and salmonellosis (1 case) were treated with CPM. The treatment by intravenous injection or drip infusion of 22 approximately 55 mg/kg/day (40 approximately 50 mg/kg/day) for mean 6 days resulted in 100% of good response in 15 cases of RTI and in 88% of good response in 8 cases of UTI. S. aureus, H. influenzae, E. coli, Proteus, Klebsiella and Salmonella group B were isolated from the culture of sputum or urine in the patients, and they were all eradicated by the treatment with CPM. No side effects were observed except eosinophilia in 1 case and the elevation of GOT and GPT in 1 case.     

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.     

Clinical evaluation for T-1982 (cefbuperazone) in the field of pediatric infection

T-1982 (cefbuperazone), a new injectable cephamycin antibiotic, was employed for bacterial infections in children, and the following results were obtained. 1. When administered intravenously at a dose of 20 mg/kg to a 6-year-old female child, serum levels were 62 micrograms/ml at 30 minutes, 39 micrograms/ml at 1 hour, 17.6 micrograms/ml at 2 hours, 6.8 micrograms/ml at 4 hours and 2.9 micrograms/ml at 6 hours with serum half-life (T 1/2) of 76 minutes. Urinary excretion rates were 41.0, 5.3% and 2.4% respectively at 0-2, 2-4 hours and 4-6 hours, and urinary levels were 820 micrograms/ml, 182 micrograms/ml and 310 micrograms/ml, respectively. The total urinary recovery within 6 hours was 48.7%. 2. A total of 11 cases of pediatric infections was treated with T-1982. The clinical efficacy evaluated for 9 cases, excluding 2 cases of non-bacterial infections, was as follows; excellent in 4, good in 1 out of 5 cases of pneumonia, good in 1 case of cervical purulent lymphadenitis, and excellent in 1, good in 1, poor in 1 out of 3 cases of urinary tract infection. 3. As side effect, mild diarrhea in 1 case and slight elevation of GOT, GPT in 2 cases were observed. 4. These results suggest that T-1982 is of good use for bacterial infections in children and the expected efficacy is obtained at a dose of 20 mg/kg 3 times a day.     

Laboratory and clinical studies on cefodizime in the pediatric field

Laboratory and clinical studies on cefodizime (CDZM, THR-221), a newly developed cephem antibiotic, were done. The results obtained are summarized as follows: 1. Absorption and elimination were examined in a total of 5 cases including a case of 10 mg/kg intravenous drip infusion for 30 minutes, 2 cases of 20 mg/kg rapid intravenous injection and 2 cases of 40 mg/kg drip infusion for 30 minutes. Maximum serum levels were attained immediately after drip infusion or rapid injection. Cmax's were 119.2 micrograms/ml for 10 mg/kg, 374.9 micrograms/ml or 255.7 micrograms/ml for 20 mg/kg, and 321.3 micrograms/ml or 431.8 micrograms/ml for 40 mg/kg. These values were determined using an high performance liquid chromatography (HPLC) method. In general, values using the bioassay were higher than those with the HPLC method. T 1/2 (beta)'s were between 1.74 and 1.93 hours using HPLC, and between 1.77 and 2.24 hours using bioassay. Urinary recovery rates were examined in 3 out of 5 cases. Cumulative urinary recovery rates were 57.9-90.6% with HPLC method and 50.4-88.0% with bioassay in a period of 0-8 hours after administration. 2. Clinical efficacy was evaluated in a total of 22 cases including 14 cases of respiratory tract infections, 5 cases of urinary tract infections and 3 cases of cellulitis. Clinical efficacy rate was 95.2%. Bacteriologically, pathogenic organisms were eradicated in 90.0%. As adverse reactions, 1 angular stomatitis, 1 diarrhea and 1 loose stool were noted. Abnormal laboratory test values detected were 1 case of increased GPT and 1 case of increased GOT and GPT.     

Experimental and clinical evaluation of cefsulodin in the pediatric field

Antimicrobial, pharmacokinetic and clinical evaluation of cefsulodin (CFS) was made and the following results were obtained. 1. Antimicrobial activity of CFS against P. aeruginosa was similar to a little lower than that of GM. Antimicrobial activity of CFS against S. aureus was similar to that of SBPC and against E. coli CFS showed lower antimicrobial activity. 2. Twenty or 50 mg/kg CFS was administered by 1 hour intravenous drip infusion. Average serum levels at the completion of the infusion were 35.1 +/- 8.0, 114.5 +/- 36.1 micrograms/ml and 1.6 +/- 0.7, 4.5 +/- 3.2 micrograms/ml at 6 hours afterward with the half life times of 1.50, 1.29 hours respectively. In case of 12.1 mg/kg 1 hour intravenous drip infusion, peak serum level was 13.4 micrograms/ml at the completion of infusion, and the concentration in the sputum was 1.0 micrograms/ml at 5 hours after completion of infusion. Average serum levels of CFS by one shot infusion of 20 mg/kg were 58.4 +/- 6.8 micrograms/ml, 2.7 +/- 2.5 micrograms/ml at 15 minutes and 6 hours after injection respectively. Half-life time was 1.54 hours. Average urinary excretion rates of CFS were 64.4%, 64.2% and 48.9% up to 6 hours after 1 hour intravenous drip infusion of 20 mg/kg, 50 mg/kg CFS and one shot intravenous of 20 mg/kg CFS respectively. 3. CFS was administered to 2 pneumonia cases caused by P. aeruginosa, i.e. one was 15 years and 11 months old male accompanying bronchial asthma and the another 4 years old male with LENNOX syndrome. Neither bacteriological nor clinical efficacy was, however, observed. Side effect as well as bacterial superinfection were not observed.     

Laboratory and clinical studies on ceftizoxime (author's transl)

The authors have carried out the laboratory and clinical studies of ceftizoxime (CZX), and obtained the following results. 1. The antibacterial activities of CZX were measured by plate dilution method against clinical isolates of S. aureus, E. coli, K. pneumoniae and P. aeruginosa. CZX inhibited the growth of S. aureus at concentrations less than 12.5 micrograms/ml, and the peak of sensitivity distribution was obtained at 3.13 micrograms/ml with an inoculum size of 10(6) cells/ml. And the peak sensitivity distribution of E. coli and K. pneumoniae were obtained at less than 0.1 microgram/ml and that of P. aeruginosa was obtained at 6.25 micrograms/ml. 2. Phagocytosis was determined by Quie's method. Phagocytosis of E. coli and K. pneumoniae by human polymorphonuclear neutrophil was more enhanced in the presence of 1 MIC and 1/2 MIC of CZX than of CEZ at 4 and 6 hours after incubation. 3. As for pharmacokinetic study, CZX was given by intravenous injection and drip infusion for 1 hour at a single dose of 10 mg/kg and 30 mg/kg. After intravenous injection of 10 mg/kg and 30 mg/kg of CZX, the mean peak serum levels were 19.1 +/- 3.4 micrograms/ml and 69.1 micrograms/ml at 30 minutes, and half-life times were 1.20 hours and 1.35 hours, respectively. After 1 hour drip infusion of 10 mg/kg and 30 mg/kg of CZX, the mean peak serum levels were 28.8 +/- 3.6 micrograms/ml and 60.9 +/- 5.9 micrograms/ml at the end of infusion, and half-life times were 1.40 hours and 1.77 hours, respectively. The mean urinary excretion rates were between 75.3% and 101% up to 6 hours after intravenous injection and drip infusion. 4. CZX was given to 4 cases with tonsillitis, 3 with pneumonia, 1 with enteritis, 4 with U.T.I., totaling 21 cases. A daily dose of CZX between 350 mg and 2,000 mg was given for 3 to 5 days. Clinical results obtained were good in all cases. No side effects and abnormal laboratory findings were observed.     

Studies on sulbactam/cefoperazone in the field of pediatrics

Microbiological, pharmacokinetic and clinical studies on sulbactam/cefoperazone (SBT/CPZ) were carried out in the field of pediatrics. Antimicrobial activity The MIC80 of SBT/CPZ was 6.25 micrograms/ml for clinically isolated 24 strains of S. aureus (24 beta-lactamase producing strains), 0.39 micrograms/ml for 17 strains of S. pyogenes, 3.13 micrograms/ml for 24 strains of E. coli (22 beta-lactamase producing strains), 3.13 micrograms/ml for 22 strains of K. pneumoniae (22 beta-lactamase producing strains), 1.56 micrograms/ml for 22 strains of P. mirabilis and 0.20 microgram/ml for 15 strains of H. influenzae (13 beta-lactamase producing strains). In comparison with CPZ in respect to the MIC, SBT/CPZ exhibited synergistic effect on 31 strains out of 81 beta-lactamase producing strains (included 6 strains of S. aureus, 9 of E. coli, 5 of K. pneumoniae and 11 of H. influenzae) which was scarcely observed against 43 non-beta-lactamase producing strains. Absorption and excretion Serum levels and urinary excretion of SBT/CPZ were studied in 7 children aged 5 to 12 years. The mean serum concentration of SBT at 15 minutes following a single intravenous injection of 10 mg/kg of SBT/CPZ was 14.2 micrograms/ml and that of CPZ was 30.4 micrograms/ml. The mean urinary recovery rates at 6 hours following the intravenous injection were 57.8% and 18.3%, respectively. The mean serum concentrations of SBT and CPZ after 1-hour infusion of 10 mg/kg of SBT/CPZ were 10.9 micrograms/ml and 17.6 micrograms/ml, respectively. The urinary recovery rates of SBT and CPZ at 7 hours after the infusion were 100.0% and 27.7% on average, respectively. The mean serum levels of SBT and CPZ at 15 minutes after a single intravenous injection of 20 mg/kg of SBT/CPZ were 25.6 micrograms/ml and 66.0 micrograms/ml, respectively and urinary elimination until up to 6 hours were 72.5% on average for SBT and 21.1% for CPZ. Clinical study SBT/CPZ was used for the treatment of a total of 20 pediatric patients aged 1 month to 14 years to evaluate its clinical effectiveness, bacteriological efficacy and adverse effects. The clinical efficacy in 6 patients with acute pneumonia, 3 with staphylococcal scalded skin syndrome, 2 each with acute purulent tonsillitis and acute pyelonephritis, 1 each with acute purulent lymphadenitis, acute sinusitis, acute bronchitis, peritonitis and acute enteritis was judged to be excellent in 15 cases and good in 3 cases with an efficacy ratio of 100%. The clinical efficacy in 6 patients whose infections were caused by beta-lactamase producing strains was judged to be excellent in all the cases.(ABSTRACT TRUNCATED AT 400 WORDS)     

Studies of meropenem in pediatric infections]

Pharmacokinetic and clinical evaluations of meropenem (SM-7338, MEPM) were carried out in pediatric patients. The following results were obtained. 1. After 30-minute intravenous drip infusion at a dose of 20 mg/kg, plasma concentrations of MEPM reached their peaks at the end of drip infusion with an average value of 48.8 +/- 3.64 micrograms/ml, and the average plasma half-life was 0.93 +/- 0.21 hour in the beta-phase. After 30-minute intravenous drip infusion at a dose of 10 mg/kg, the average peak plasma concentration was 27.7 +/- 4.33 micrograms/ml and the average plasma half-life was 0.78 +/- 0.20 hour. 2. Urinary excretion rates of MEPM after 30-minute intravenous drip infusion at doses of 20 and 10 mg/kg were 44.8 +/- 4.54% and 40.9 +/- 1.78%, respectively. 3. MEPM was administered to 13 cases (upper and lower respiratory infections, pneumonia and lymphadenitis) at daily doses between 60-90 mg/kg/day divided into 3 dosages using 30-minute intravenous drip infusion. Clinical responses were "excellent" in 12 patients, "good" in 1, hence an efficacy rate of 100% was obtained. 4. Bacteria identified in various disease cases included 12 strains of 5 species, and the eradication rate was 100%. 5. No side effects were observed in any children. Laboratory test results showed abnormalities in 2 cases with elevations of GOT and GPT. These results suggest that MEPM may be a very useful and safe drug for the treatment of pediatric infections.     

Pharmacokinetic and clinical evaluation of cefpirome in the pediatric field

Pharmacokinetic and clinical evaluations of cefpirome (CPR), a newly developed cephalosporin, were performed in the field of pediatrics. The results are summarized as follows. 1. Peak serum concentrations of CPR after a dose of 20 mg/kg via 30 minutes and that via 60 minutes intravenous drip infusion and a dose of 40 mg/kg via 60 minutes intravenous drip infusion were 80.8, 63.7 and 128.8 micrograms/ml, respectively, with half-lives being 1.41, 1.28 and 1.79 hours, respectively. Urinary excretion rates for CPR in the first 6 hours after administration ranged 66.7-77.1%. 2. The clinical efficacy rate in pediatric infections obtained at daily dose levels ranging 55.6-166.7 mg/kg was 95.7%. 3. The eradication rate for 22 strains identified in the study was 95.5%. 4. Side effects were found in 2 cases of diarrhea. The abnormal laboratory test results were observed in 5 cases with 7 test items (increased number of platelets; 2 cases, increased activity of GOT; 2 cases and increased activity of GPT; 1 case). According to these results, CPR was considered to be a useful antimicrobial agent in pediatric infections.     

Studies on panipenem/betamipron in the field of pediatrics]

Pharmacokinetic and clinical studies in pediatrics were performed on panipenem/betamipron (PAPM/BP), a combined drug of a carbapenem antibiotic (panipenem) and organic ion inhibitor (betamipron) at a weight ratio of 1:1. 1. Plasma levels and urinary excretion were studied when PAPM/BP, at 10 mg/10 mg/kg (4 cases) or 20 mg/20 mg/kg (5 cases), was administered using intravenous drip infusion in 30 minutes to 9 children (4-14 years old). The plasma PAPM level at the end of drip infusion was 30.75 +/- 4.98 micrograms/ml in the cases administered with 10 mg/10 mg/kg and 68.72 +/- 5.73 micrograms/ml in the cases administered with 20 mg/20 mg/kg. Drug concentrations then gradually decreased with half-lives of 1.08 +/- 0.09 hours and 0.98 +/- 0.02 hour, and reached 0.39 +/- 0.14 micrograms/ml and 0.62 +/- 0.06 micrograms/ml, respectively, after 5.5 hours. Plasma BP levels at the end of drip infusion was 18.93 +/- 3.75 micrograms/ml in the cases administered 10 mg/10 mg/kg and 37.09 +/- 2.68 micrograms/ml in the cases administered 20 mg/kg, and half-lives were 0.55 +/- 0.07 hour and 0.61 +/- 0.03 hour, respectively; the plasma BP level could not be determined in any cases after 5.5 hours. Mean urinary recovery rates of PAPM in the first 6 hours after the start of intravenous drip infusion were 33.0 +/- 6.1% in the cases administered 10 mg/10 mg/kg and 21.8 +/- 2.3% in the cases administered 20 mg/20 mg/kg and those of BP were 77.0 +/- 2.4% and 76.6 +/- 7.3%, respectively. 2. When PAPM/BP, was administered at 31.3 mg/31.3 mg/kg thought by intravenous drip infusion in 30 minutes to 1 case of purulent meningitis, PAPM levels were 0.76 micrograms/ml at the end of drip infusion but varied between 0.80 to 1.97 micrograms/ml 30 minutes after the end of drip infusion during 8 days of treatment. 3. PAPM/BP was administered to 43 cases, 47 diseases of bacterial infections in the domain of pediatrics to study its clinical efficacy, bacteriological efficacy and adverse reactions. Single doses were 5.2mg/5.2mg to 31.3 mg/31.3 mg/kg; frequencies of administration were 3 to 4 times a day, and durations of administration were 3 1/3 to 11 days; and total dosages ranged between 1.125 g/1.125 g and 11.0 g/11.0 g.(ABSTRACT TRUNCATED AT 400 WORDS)     

Pharmacokinetic study of cefsulodin in children

Cefsulodin (CFS), a cephem antibiotic, was administered to 26 children aged from 11 months to 11 years by intravenous injection or intravenous 1-hour drip infusion in doses of 15 and 50 mg/kg body weight to investigate serum and urinary concentrations. The following results were obtained. Serum concentration The serum concentrations of CFS at 5 minutes after intravenous injection of 15 and 50 mg/kg were 57.1 and 224.2 micrograms/ml, respectively. The biological half-lives (T 1/2 beta) were 1.28 and 1.12 hours. The serum concentration of CFS after intravenous 1-hour drip infusion reached a peak at the end of infusion, i.e. 29.9 micrograms/ml for 15 mg/kg and 121.9 micrograms/ml for 50 mg/kg, and T 1/2 beta were 1.22 hours for 15 mg/kg and 1.27 hours for 50 mg/kg. The AUC was proportional to the doses for both intravenous injection and intravenous drip infusion. The serum clearance was about twice the value in adults and the distribution volume was about 1.5 times as large. Urinary excretion The urinary excretion up to 6 hours after administration was: 69.0% for 15 mg/kg and 61.9% for 50 mg/kg in cases of intravenous injection, and 62.4% for 15 mg/kg and 71.1% for 50 mg/kg in cases of intravenous 1-hour drip infusion. The percent urinary excretion was similar to that in adults.     

Pharmacokinetics and clinical studies on CS-1170 (author's transl)]

The authors have carried out the pharmacokinetics and clinical studies of CS-1170. The results were as follows; CS-1170 was given by drip infusion for 1 hour dose of 20 mg per kg body weight to 3 children. The maximum blood level was reached at one hour after drip infusion. This blood levels were 38 micrograms/ml, 68 micrograms/ml and 86 micrograms/ml, respectively, (mean 64 micrograms/ml), and level at 2 hours, 11.5 micrograms/ml, 9.4 micrograms/ml, 16 micrograms/ml respectively, (mean 12.3 micrograms/ml), the blood level at 6 hours was not determined. The urinary excretion rates were 94.8 approximately 96.8% up to 6 hours after drip infusion dose of 20 mg per kg body weight. CS-1170 was effective in 7 of 8 cases with pediatric bacterial infections. An ineffective case was a pneumonia due to Serratia marcescens. No side effect was observed except for 2 cases with diarrhea and one case with elevation of GOT and GPT.