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Fundamental and clinical studies on aztreonam (AZT), a new monobactam antibiotic, were performed in the pediatric field. The MICs of AZT were assessed against the clinically isolated strains in the pediatric infections. AZT showed an excellent antibacterial activity against Gram-negative bacteria, i.e., against E. coli (20 strains), K. pneumoniae (9), P. mirabilis (16), P. vulgaris (5), P. aeruginosa (10), S. typhimurium (4) and H. influenzae (11); the MICs of AZT against the above strains were less than 0.39 microgram/ml, 0.10 microgram/ml, 0.024 microgram/ml, 0.024 microgram/ml, 6.25 micrograms/ml, 0.10 microgram/ml and 0.10 microgram/ml, respectively. However, antibacterial activity of AZT against Gram-positive bacteria was inferior to that against Gram-negative bacteria, i.e., against the strains of S. aureus (16) and S. pyogenes (4), those MICs were more than 400 micrograms/ml and 3.13 micrograms/ml, respectively. Serum concentrations and urinary excretion of AZT were measured in 2 children aged 7 and 11 years after a single intravenous injection at the dose of 20 mg/kg. The mean serum concentration of AZT followed by the injection 62.5 micrograms/ml at 1/4 hour, 28.5 micrograms/ml at 1/2 hour, 16.5 micrograms/ml at 1 hour, 12.0 micrograms/ml at 2 hours, 3.6 micrograms/ml at 4 hours and 1.1 micrograms/ml at 6 hours, respectively. The mean half-life (beta-phase) was 1.24 hours. The mean urinary concentrations after the injection were 5,000 micrograms/ml in 0-2 hours, 1,650 micrograms/ml in 2-4 hours and 611 micrograms/ml in 4-6 hours and the mean urinary recovery rate up to 6 hours was 61.2%. These results in our studies were considered to be comparable with those reported in adults. In our clinical studies, AZT was administered to a total of 14 cases, i.e., acute pneumonia (4 cases), acute pyelonephritis (4), acute enteritis (5) and acute sppurative cholangitis (1). Clinical effect of AZT was excellent or good in 13 cases except fair in 1 case with acute enteritis and the efficacy rate (excellent and good) was 92.9%. With regard to bacteriological effect, all the strains of H. influenzae (3), E. coli (2), P. mirabilis (1) and P. vulgaris (1) were eradicated, but, S. typhimurium (4) was not eradicated. Neither side effect nor abnormal laboratory findings were observed during the study.

Fundamental and clinical studies were carried out on ceftazidime ( CAZ ), a new cephalosporin, in the field of pediatrics. 1. Antimicrobial activity MICs of CAZ were determined for clinical isolates of 24 strains of S. aureus, 15 of S. pyogenes, 8 of H. influenzae, 22 of E. coli, 20 of K. pneumoniae, 18 of P. mirabilis, 3 of P. morganii, and 21 of P. aeruginosa, and compared with those of the control drugs, i.e. CEZ, CXM, CMZ, CTX, LMOX and CMX. For P. aeruginosa, CPM, CFS and GM were also employed as the control drugs. CAZ was as active as CTX, LMOX and CMX, its MICs distributing in the range not higher than 0.10 microgram/ml for H. influenzae, 0.78 microgram/ml for E. coli, 0.39 microgram/ml for K. pneumoniae, 0.10 microgram/ml for P. mirabilis, and 0.10 microgram/ml for P. morganii in all the strains. Against P. aeruginosa, CAZ showed MICs in the range between 0.39 and 3.13 micrograms /ml, which showed activity higher than that of CTX, LMOX , CPM, CMX and GM, and comparable to that of CFS. Against S. pyogenes, CAZ was as active as all the control drugs except for LMOX , its MICs for all strains tested being 0.20 microgram/ml or below. Against S. aureus, CAZ was slightly more active than LMOX , but less active than the other control drugs, its MICs being relatively high ranging from 6.25 to 50 micrograms/ml. 2. Pharmacokinetics After a one-shot intravenous injection of CAZ 20 mg/kg, serum levels and urinary excretion were studied in 3 children aged 6 to 9 years, and CSF levels were determined in 2 children aged 6 to 7 years with aseptic meningitis. The mean serum levels of CAZ were 85.3 micrograms/ml at 1/4 hour, 53.3 micrograms/ml at 1/2 hour, 32.0 micrograms/ml at 1 hour, 16.1 micrograms/ml at 2 hours, 5.3 micrograms/ml at 4 hours, and 2.0 micrograms/ml at 6 hours, with the mean half-life of 1.18 hours. The mean urinary levels were 9,700 micrograms/ml at 0 to 2 hours, 803 micrograms/ml at 2 to 4 hours, 540 micrograms at 4 to 6 hours, and the mean urinary recovery rate during the first 6 hours was 83.9%. The CSF levels at 1 hour after intravenous injection were 0.44 microgram/ml in acute stage and 0.10 to 0.22 microgram/ml in convalescent stage. 3. Clinical study Thirty-one pediatric patients with bacterial infections were treated with CAZ , and the clinical efficacy, bacteriological response, and side effects were evaluated.(ABSTRACT TRUNCATED AT 400 WORDS)

Basic and clinical studies were carried out on latamoxef (LMOX) in relation to the use of this antibiotic in the treatment of infections in newborn infants. The results were as follows. The MICs of LMOX were determined for various clinical isolates of Gram-negative bacteria: 22 strains of E. coli, 18 strains of K. pneumoniae, 4 strains of K. oxytoca, 19 strains of P. mirabilis, 4 strains of P. vulgaris, 5 strains of P. morganii and 3 strains of C. freundii and 60 strains of H. influenzae. The MIC distributions against all of these strains for each species were 0.1, 0.2, 0.1, 0.2, 0.1, 0.1, 6.25 and 0.78 microgram/ml or less, respectively. The antibacterial activity of LMOX against all of these Gram-negative isolates was thus found to be excellent. For 38 strains of P. aeruginosa, the MIC distribution was from 6.25 to 200 micrograms/ml; accordingly, although this antibiotic does show antibacterial activity against this microbe, it is not very potent. As Gram-positive bacteria, 28 clinical isolates of S. pyogenes and 34 strains of S. aureus were tested; their respective MIC distributions were 0.39--1.56 micrograms/ml and 3.13--25 micrograms/ml. Therefore, it is clear that the antibacterial activity of LMOX against these Gram-positive bacteria is not as good as against the above-mentioned Gram-negative species. LMOX was injected intravenously as a one-shot dose of 20 mg/kg to 5 newborn infants (ranging in age from 0 to 13 days) and to 2 suckling infants (49 and 60 days of age), and then the concentration of the drug in the serum was monitored with time. The mean serum concentrations in the newborn group at various times were as follows: 38.5 micrograms/ml at 0.5 hour, 31.6 micrograms/ml at 1 hour, 26.9 micrograms/m l at 2 hours, 17.8 micrograms at 4 hours and 15.5 micrograms/ml at 6 hours. For the 2 suckling infants, the mean values at those same time points were 30.5, 23.9, 16.3, 7.4 and 4.0 micrograms/ml. In addition the value for the mean serum half-life was 4.46 hours in the newborn infant group and 1.96 hours in the suckling infant group. The urinary recovery rate was 32.3% in the newborn infant group and 49.7% in the suckling infant group during 6 hours or 8 hours.(ABSTRACT TRUNCATED AT 400 WORDS)

Fundamental and clinical studies of cefpiramide (CPM), a new cephem antibiotic, were carried out in the field of pediatrics. 80% MICs of CPM against S. aureus, S. pyogenes, H. influenzae, E. coli, K. pneumoniae and P. aeruginosa were 1.56, 0.05, 0.39, 6.25, 0.78 and 25 micrograms/ml, respectively. Serum concentration of CPM after intravenous injection at a dose of 20 mg/kg to 3 children was 103.7 +/- 9.1 micrograms/ml at 15 minutes and 13.4 +/- 5.0 micrograms/ml at 8 hours, with half-life of 3.11 +/- 0.83 hours. The excretion rate of CPM into urine was 16.40 +/- 7.31% within 8 hours. The transfer of CPM to cerebrospinal fluid was 0.1 approximately 0.2 micrograms/ml at 1 hour after intravenous injection at a dose of 20 mg/kg to patients with Aseptic meningitis, and 0.4 approximately 4.0 micrograms/ml at 1 hour approximately 3 hours 15 minutes after intravenous injection at a dose of 50 mg/kg to patients with purulent meningitis. Clinical effects of CPM on 37 patients with various infections were excellent in 28 cases, good in 6 cases, fair in 2 cases and poor in 1 case. The effective rate (excellent and good) was 91.9%. Bacteriologically, the eradication rate in 23 isolated organisms was 95.5%. No side effects and abnormalities of laboratory findings were noted. It was concluded that CPM has a broad spectrum antibacterial activity both in vitro and in vivo.

A fundamental and clinical study of ceftizoxime (CZX) suppositories was performed in pre-school and school-age children. The average time courses of CZX serum and urinary concentrations after administration of CZX suppository 250 mg (i.e. per kg body weight doses of 8.3-10.9 mg) to 4 school-age children were as follows. Serum concentrations: 6.1 micrograms/ml at 15 minutes, 6.3 micrograms/ml at 30 minutes, 3.8 micrograms/ml at 1 hour, 1.7 microgram/ml at 2 hours, 0.5 microgram/ml at 4 hours and 0.2 microgram/ml at 6 hours with a biological half-life of 1.43 hours. Urinary concentrations: 885 micrograms/ml for 0-2 hours, 209 micrograms/ml for 2-4 hours and 112 micrograms/ml for 4-6 hours with an average 6-hour urinary recovery rate of 25.6%. The clinical and biological effectiveness and adverse reactions were studied in 11 infants and school-age children afflicted with various infections (acute purulent tonsillitis, 1; acute bronchitis, 3; acute pneumonia, 4; and UTI, 3). The clinical responsiveness was "excellent" in 8, "good" in 2, and "failure" was recorded in 1, with an overall efficacy of 90.9% inclusive of "excellent" and "good". The microbiological effectiveness of CZX suppositories on presumed pathogenic organisms comprising 4 strains of H. influenzae, 1 strain of H. parainfluenzae, and 3 strains of E. coli was satisfactory, as evidenced by the substantially high eradication rate of 87.5%. The only organism that survived CZX suppository treatment was 1 strain of H. influenzae which however was greatly decreased. The only side effect was diarrhea in 1 patient, which however did not necessitate withdrawal of the drug. The only laboratory test abnormality was GOT and GPT elevation in 1 patient which was normalized within 8 days. In conclusion, CZX suppositories were found to be efficacious and safe for treatment of bacterial infections in children.

Fundamental and clinical evaluation of ceftriaxone (Ro 13-9904, CTRX) was performed in the pediatric field. Antibacterial activity The MIC80 of CTRX against clinical isolates such as S. aureus (23 strains), S. pyogenes (23 strains), E. coli (20 strains), K. pneumoniae (23 strains), H. influenzae (15 strains) and P. aeruginosa (23 strains) were 6.25 micrograms/ml, 0.024 microgram/ml, 0.20 microgram/ml, 0.05 microgram/ml, less than or equal to 0.006 microgram/ml and 12.5 micrograms/ml, respectively. The antibacterial activity of CTRX was therefore poor against S. aureus and P. aeruginosa, but quite excellent against S. pyogenes, E. coli, K. pneumoniae and H. influenzae. Compared with cefotaxime (CTX), cefoperazone (CPZ), cefmetazole (CMZ), cefazolin (CEZ) and ceftazidime (CAZ), CTRX was the highest in the antibacterial activity against H. influenzae, next to CTX against S. pyogenes, E. coli and K. pneumoniae, similar to CTX, CPZ and CAZ against S. aureus and similar to CTX against P. aeruginosa. Absorption, Excretion The mean serum levels of CTRX after an intravenous one shot injection with about 20 mg/kg in 3 children aged 10 to 14 years were 160.0 +/- 23.3 micrograms/ml after 1/4 hour, 134.3 +/- 27.5 micrograms/ml after 1/2 hour, 115.0 +/- 33.2 micrograms/ml after 1 hour, 95.3 +/- 28.4 micrograms/ml after 2 hours, 75.3 +/- 14.5 micrograms/ml after 4 hours, 30.3 +/- 13.5 micrograms/ml after 12 hours and 8.2 +/- 3.1 micrograms/ml after 24 hours, while the half-life time was 5.92 +/- 0.43 hours on the average. The mean urinary levels were 1,060 +/- 461 micrograms/ml from 0 to 2 hours, 309 +/- 122 micrograms/ml from 2 to 4 hours, 375 +/- 83 micrograms/ml from 4 to 6 hours, 237 +/- 77 micrograms/ml from 6 to 12 hours and 122 +/- 23 micrograms/ml from 12 to 24 hours, the mean urinary recovery rate up to 24 hours being 38.9 +/- 13.6%. The concentration in the cerebrospinal fluid The mean levels of CTRX in the cerebrospinal fluid of the patients with purulent meningitis were 4.30 +/- 4.22 micrograms/ml 1 hour after an intravenous one shot injection with 42 to 51 mg/kg, 4.64 +/- 3.53 micrograms/ml after 3 1/2 hours to 6 hours, 3.79 +/- 2.15 micrograms/ml after 7 1/2 hours to 12 hours and 1.79 +/- 0.23 microgram/ml after 19 hours.(ABSTRACT TRUNCATED AT 400 WORDS)

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)

Fundamental and clinical studies of ceftizoxime, a new cephalosporin antibiotic, in children led to the following results. 1. Ceftizoxime compared favorably with cefazolin (CEZ) and cefmetazole (CMZ) for in vitro activity against clinically isolated strains of Staphylococcus aureus (31 strains), Escherichia coli (29), Klebsiella pneumoniae (30) and Pseudomonas aeruginosa (16). While somewhat less active against S. aureus than CEZ and CMZ, ceftizoxime was far more active than these 2 cephalosporin antibiotics against the test strains of E. coli and K. pneumoniae, which included strains resistant to the 2 drugs. Ceftizoxime was not particularly active against Ps. aeruginosa, but this seeming disadvantage was offset by the absolute ineffectiveness of the 2 reference drugs on this obstinate organism. 2. The time course of mean serum ceftizoxime levels in 3 pediatric patients of 5--10 years old given a single intravenous dose of 20 mg/kg was as follows: 45.4 micrograms/ml at 15 minutes, 40.4 micrograms/ml at 30 minutes, 22.1 micrograms/ml at 1 hour, 10.4 micrograms/ml at 2 hours, 2.9 micrograms/ml at 4 hours and 0.9 microgram/ml at 6 hours. The mean serum half life was 1.12 hours. The mean urinary levels of ceftizoxime at serial 2-hour collection intervals were as follows: 2,477 micrograms/ml for 1--2 hours, 1,235 micrograms/ml for 2--4 hours and 462 micrograms/ml for 4--6 hours. The mean urinary recovery up to 6 hours was 61.0%. 3. The clinical response of 28 children with infection to ceftizoxime treatment was 'excellent' in 22 children, 'good' in 4, and 'poor' in 2. These children comprised 11 with acute pneumonia, 3 with acute bronchitis, 4 with acute pyelonephritis, 2 each with acute purulent arthritis and acute enterocolitis, and 1 each with acute purulent tonsillitis, acute purulent lymphadenitis, furunculosis, subcutaneous abscess, subdural abscess and sepsis. The overall rate of effectiveness was 92.9%. Successfully eradicated strains in the bacteriological sense consisted of 4 strains each of H. influenzae and E. coli, 1 strain each of P. morganii, S. pneumoniae and S. pyogenes, 1 of the 2 strains of S. enteritidis, and 1 of the 3 strains of S. aureus. The overall rate of bacteriological effectiveness was 81.3%. No clinical side effects were observed. Changes in laboratory test findings included slightly and transiently elevated GOT and GPT in 1 child and GOT alone in another child.

Bacteriological, pharmacokinetic, and clinical studies of cefixime (CFIX), a newly developed oral cephalosporin, was conducted in our pediatric department as outlined below. Bacteriology The prevalent MICs of CFIX by microbiological species, compared with those of the reference drugs, were detailed below. Against 16 strains of S. aureus, the MICs averaged 6.25 micrograms/ml, and were found to be nearly the same as the MICs of amoxicillin (AMPC) but higher than those of cephalexin (CEX) and cefaclor (CCL). For 4 strains of S. pyogenes, the MICs averaged 0.05 microgram/ml, and were higher than the MICs of AMPC but lower than those of CEX and CCL. Mean MICs of CFIX against other clinical isolates were lower than those of CEX, CCL, or AMPC; E. coli (20 strains), 3.13 micrograms/ml; K. pneumoniae (9), 0.10 microgram/ml; P. mirabilis (16), 0.025 microgram/ml; P. vulgaris (5), 0.10 microgram/ml; H. influenzae (11), 0.05 microgram/ml; and S. typhimurium (4), 0.10 microgram/ml. The MICs of CFIX against 10 strains of P. aeruginosa were distributed at and above 25 micrograms/ml, a range much lower than greater than or equal to 100 micrograms/ml for CEX, CCL, or AMPC. Pharmacokinetics The serum concentrations and urinary recovery were studied in 3 children ranging from age 7 to 13. They were given CFIX on empty stomach in 2 different single doses of 3 and 6 mg/kg in a cross-over design. Average serum CFIX concentrations were dose-dependent, as evidenced by the respective peak concentrations of 1.70 microgram/ml for a 3 mg/kg dosage and 2.72 micrograms/ml for 6 mg/kg, which were attained 4 hours after the administration of the drug. The average half-lives of CFIX in the serum were 3.09 hours and 3.11 hours, respectively, and the 12-hour serum concentrations were 0.32 microgram/ml and 0.77 microgram/ml, respectively, for the 2 different dose levels. The average 12-hour urinary recovery was 25.2% and 22.3%, respectively. Clinical study Clinical effectiveness, bacteriological effectiveness, and side effects were studied in 27 children with infection including 4 patients with acute pharyngitis, 13 with acute purulent tonsillitis, 5 with acute pneumonia, 3 with urinary tract infection, and 1 each with acute rhinitis and acute bronchitis. One child with acute pneumonia (Mycoplasma pneumonia) was excluded from the study. The therapeutic effectiveness was "excellent" in 21, "good" in 3, "fair" in 1, and "poor" in 1, with an effectiveness rate of 92.3%.(ABSTRACT TRUNCATED AT 400 WORDS)

Fundamental and clinical studies of aspoxicillin (ASPC, TA-058), a new penicillin antibiotic, were performed in pediatric field. Antimicrobial activity MIC of ASPC was compared with that of piperacillin (PIPC), ampicillin (ABPC) and carbenicillin (CBPC) for clinical isolates of S. aureus (24 strains), S. pyogenes (22 strains), H. influenzae (18 strains), E. coli (21 strains) and K. pneumoniae (23 strains). MIC of ASPC against S. pyogenes was distributed in less than 0.39 microgram/ml and this numerical value of MIC was very superior. MIC distributions of ASPC against S. aureus, H. influenzae and E. coli had 2 peaks respectively. It was presumed that the results are due to an existence of beta-lactamase producing strains. The sensitive strains in those were distributed in less than 1.56-12.5, less than or equal to 0.10 and 0.78-3.13 micrograms/ml, respectively, and those numerical value of MIC was superior. While against K. pneumoniae, all strains were distributed in more than 12.5 micrograms/ml and the antimicrobial activity of ASPC was very inferior. ASPC was as active as PIPC and ABPC against S. pyogenes, but more active then CBPC, ASPC was less active against S. aureus than PIPC and ABPC, but more active than CBPC. And ASPC was less active against H. influenzae and E. coli than PIPC, but more active than ABPC and CBPC. Against K. pneumoniae, strains that showed somewhat low numerical value of MIC at only PIPC were observed, but antimicrobial activities of ABPC and CBPC, as well as ASPC were very inferior. Absorption and excretion Serum level and urinary excretion of ASPC in 6 pediatric patients of 4 months to 12 years of age after one shot intravenous injection of 20 mg/kg were examined. The serum mean levels were 51.7 micrograms/ml at 1/4 hour, 38.2 micrograms/ml at 1/2 hour, 22.9 micrograms/ml at 1 hour, 3.0 micrograms/ml at 4 hours and 1.0 microgram/ml at 6 hours after injection, respectively. The mean half-life of serum level was 1.03 hours. The mean urinary levels were 4,646 micrograms/ml for 0-2 hours, 1,773 micrograms/ml for 2-4 hours and 299 micrograms/ml for 4-6 hours. The mean urinary recovery rate within 6 hours after injection was 64.7%. Clinical studies In order to evaluate clinical response, bacteriological response and side effects, ASPC was applied to 28 cases, i.e., 5 cases of acute purulent tonsillitis, 2 cases of acute purulent otitis media, 2 cases of acute bronchitis and 19 cases of acute pneumonia.(ABSTRACT TRUNCATED AT 400 WORDS)

Fundamental and clinical studies of cefotetan (CTT) were made in pediatric field and the following results were obtained. Antimicrobial activity MIC80 values of CTT against clinically isolated S. aureus (32 strains), E. coli (33 strains) and K. pneumoniae (33 strains) were 25, 0.1 and 0.1 microgram/ml respectively. Antimicrobial activities of CTT against E. coli and K. pneumoniae were superior to those of CMZ, though the activity against S. aureus was inferior to that of CMZ. Pharmacokinetics When 20 mg/kg of CTT was administered to 3 children, who were 3 to 8 years of age, by a intravenous bolus injection, the mean serum concentrations of the drug after 1/2, 1, 2, 4, 6 and 8 hours were 110.7 +/- 9.2, 81.7 +/- 10.1, 50.0 +/- 7.5, 25.3 +/- 4.6, 14.9 +/- 5.5 and 7.7 +/- 2.8 micrograms/ml respectively, and the mean half-life (beta) was 2.01 +/- 0.32 hours. The mean concentrations of the drug in urine after 0-2, 2-4, 4-6 and 6-8 hours were 1,377 +/- 787, 1,045 +/- 689, 1,067 +/- 680 and 358 +/- 80 micrograms/ml respectively, and the mean recovery rate by 8 hours was 67.3 +/- 16.2%. Clinical study CTT was administered to 42 children of 2 monthes to 14 years of age, and clinical response, bacteriological effect and adverse reaction of the drug were studied. Clinical effects were evaluated in 8 cases of acute purulent tonsillitis, each 1 case of acute otitis media and acute bronchitis, 16 cases of acute bronchopneumonia or acute lobar pneumonia, 9 cases of acute pyelonephritis and 1 case of erysipelas, the results were excellent in 30 cases, good in 3, fair in 2 and poor in 1, and thus 91.7% of efficacy rate was obtained. Out of suspected causative organisms including 12 strains of H. influenzae, 1 strain of H. parainfluenzae, 7 strains of E. coli, 2 strains of S. pyogenes, 2 strains of S. pneumoniae and each 1 strain of S. epidermidis and S. faecalis, all the strains except each 1 strain of H. influenzae and S. faecalis disappeared after the treatment. Thus 92.3% of eradication rate was obtained. No side effects were recognized. Though abnormal laboratory findings were observed in 3 cases (7.1%), including elevation of GOT and GPT in 2 cases and eosinophilia in 1 case, those findings came to be normal after the treatment.

Pharmacokinetic and clinical studies on cefmenoxime (CMX) in neonates and infants were conducted. 1. CMX 20 mg/kg was administered by intravenous bolus injection to 6 neonates (with ages 2 to 20 days) and 5 infants (with ages 36 to 107 days) and its serum concentration and urinary excretion rates were determined. In the neonates, serum concentrations of CMX after intravenous administration reached peak levels of 48.2 to 90.7 micrograms/ml (mean 70.4 +/- 14.3 micrograms/ml) in 1/4 hour, then declined with half-lives of 1.27 to 5.19 hours (mean 2.28 +/- 1.56 hours), and were 3.6 to 16.9 micrograms/ml (mean 8.3 +/- 6.0 micrograms/ml) at 6 hours. In the infants, serum concentrations at 1/4 hour were 67.5 to 111.0 micrograms/ml (mean 95.5 +/- 18.0 micrograms/ml); half-lives were 0.64 to 0.94 hour (mean 0.81 +/- 0.13 hour); and the serum concentrations at 6 hours were 0.2 to 1.1 micrograms/ml (mean 0.7 +/- 0.4 micrograms/ml). Mean peak serum concentrations in the neonates tended to be lower than those in the infants, but higher than those in children. Regarding the age differences of serum concentrations due to age in the neonates, their peak levels tended to be lower in younger ones. Half-lives were shorter in older subjects and, in early infancy, approached values observed in children. Urinary recovery rates in the first 6 hours after intravenous administration ranged from 43.6 to 87.5% (mean 61.6 +/- 14.6%) in the neonates and from 52.1 to 90.8% (mean 78.0 +/- 15.1%) in the infants. Thus, recovery rates were high even in younger subjects and tended to be higher in older subjects. 2. CMX was administered to 27 neonates and 4 infants to investigate its clinical effect, bacteriological effect and side effects. Clinical efficacy ratings of the drug in 19 neonate cases that could be evaluated (1 with purulent meningitis, 2 with suspected septicemia, 1 with acute bronchitis, 12 with acute pneumonia, 1 with impetigo, 1 with periumbilical abscess and 1 with acute pyelonephritis) were "excellent" in 14 cases, "good" in 4, and "poor" in 1. The efficacy rate covering "excellent" and "good" was 94.7%. In 4 infants (2 with acute pneumonia, 1 with periumbilical abscess and 1 with acute pyelonephritis), "excellent" was obtained in 2 cases and "good" in 2 cases. Thus, all the cases showed "good" or higher ratings. Bacteriologically, 1 strain of Staphylococcus aureus and 3 strains of Escherichia coli in neonates were eradicated while, in infants, 1 strain of S. aureus persisted but 1 of E. coli was eradicated.(ABSTRACT TRUNCATED AT 400 WORDS)

Evaluations of ceftazidime (CAZ) in a few different categories were carried out in neonates. Single doses of 20 mg/kg of CAZ were administered to 8 neonates (day-age range: 1-26) and 3 infants (day-age range: 45-119) by bolus intravenous injection. Mean serum concentrations of CAZ at 15, 30 min., 1, 2, 4 hours and 6 hours were 51.6 +/- 9.2, 48.1 +/- 8.7, 47.9 +/- 7.8, 38.2 +/- 6.5, 20.2 +/- 4.0 micrograms/ml, and 15.3 +/- 5.8 micrograms/ml, respectively, in the neonates, and 51.1 +/- 10.3, 44.7 +/- 6.8, 35.5 +/- 4.1, 21.4 +/- 2.0, 8.6 +/- 1.0 micrograms/ml and 3.5 +/- 0.8 micrograms/ml, respectively, in the infants. Mean half-lives of CAZ in serum were 2.87 +/- 0.77 hours in the neonates and 1.39 +/- 0.10 hours in the infants, and mean urinary recovery rates in the first 6 hours were 60.5 +/- 16.0%, and 76.8 +/- 39.6% in the neonates and the infants, respectively. When individual differences are taken into consideration, no significant difference exists among 30-minute serum concentrations of neonates of different day-ages, and these concentrations were not significantly different from those in infants and older children. Half-lives of CAZ in sera decreased rapidly with the advances of the day-ages of the neonates, and the half-life at an age of 1-month should be similar to that in older children. The CAZ was administered to 2 cases of suspected sepsis, 7 of acute pneumonia, 1 of acute pyelonephritis, 1 of cellulitis, and 2 of idiopathic respiratory distress syndrome, and clinical efficacies were excellent in all the cases except for 2 cases excluded from the assessment. S. pyogenes (1), E. coli (1) and S. aureus (1) suspected as causative organisms were eradicated by the treatment with CAZ. Neither clinical adverse effects nor abnormal laboratory findings were observed in any case. From the above results, CAZ is considered to be an antibiotic with high efficacy and safety in the treatment of neonates.

Fundamental and clinical studies on BRL 25000 granules were carried out in the pediatric field. BRL 25000 is a formulation comprising 1 part of clavulanic acid (CVA) and 2 parts of amoxicillin (AMPC). The MICs of BRL 25000 and AMPC were assessed against 24 clinically isolated strains of S. aureus (including 23 beta-lactamase producing strains), 22 S. pyogenes, 20 E. coli (8 beta-lactamase producing strains), 24 K. pneumoniae (24 beta-lactamase producing strains), 20 H. influenzae (6 beta-lactamase producing strains). BRL 25000 showed MIC80 (cumulatively 80% of strains were inhibited) at 6.25 micrograms/ml against S. aureus, less than or equal to 0.10 micrograms/ml against inst S. pyogenes, 12.5 micrograms/ml against E. coli, 6.25 micrograms/ml against K. pneumoniae and 0.39 micrograms/ml against H. influenzae. BRL 25000 showed no improvement in MIC terms against beta-lactamase nonproducing strains compared with AMPC. However, BRL 25000 was markedly more effective against beta-lactamase producing strains. Thus BRL 25000 was up to 8 fold more active against S. aureus, 2 to 64 fold against E. coli, 4 to 128 fold against K. pneumoniae, 4 to 16 fold against H. influenzae than AMPC. Following oral administration of BRL 25000 granules (at a dose level of 12.5 mg/kg) to 2 children aged 9 and 11 years, the mean peak serum concentrations of AMPC and CVA were 8.33 +/- 2.43 micrograms/ml and 4.44 +/- 1.65 micrograms/ml respectively 1 hour after dosing. The half-lives of AMPC and CVA were 1.35 +/- 0.42 hours and 0.91 +/- 0.05 hour, respectively. The urinary excretion was 48.21 +/- 3.83% for AMPC and 16.90 +/- 7.06% for CVA in the first 6 hours after administration. In clinical studies, 23 pediatric patients aged 2 months to 12 years with bacterial infections were treated with BRL 25000 granules and the clinical effectiveness, bacteriological response and side effects were evaluated. The clinical response was assessed in 23 cases, 3 with acute rhinitis, 6 with acute purulent tonsillitis, 5 with acute bronchitis, 4 with acute pneumonia, 3 with impetigo, 1 with furunculosis and 1 with periproctal abscess. Results were excellent in 13 cases, good in 7, fair in 3 and hence the efficacy rate (excellent and good cases) was 87.0% (20/23). In particular the clinical response in 9 cases with infections due to beta-lactamase producing organisms was excellent in 6, good in 2, fair in 1 and the efficacy rate was 88.9% (8/9).(ABSTRACT TRUNCATED AT 400 WORDS)