Systemic lupus erythematosus with cytophagic histiocytic panniculitis successfully treated with high-dose glucocorticoids and cyclosporine A.

A 37-year-old male with systemic lupus erythematosus (SLE) presented with high fever, subcutaneous indurations, anemia, thrombocytopenia, elevated liver enzymes and hyperferritinemia. Skin biopsy revealed hemophagocytic histiocytes in the adipose tissues. The patient was diagnosed with SLE with cytophagic histiocytic panniculitis (CHP). Treatment with high-dose glucocorticoids and cyclosporine A induced remission of SLE and CHP. CHP is generally a systemic disorder affecting subcutaneous adipose tissues with a high mortality rate. However, based on the present and previously reported cases, we believe that intensive immunosuppression can ameliorate CHP that occurs as a skin manifestation of SLE.

Combinatory effects of androgen receptor deficiency and hind limb unloading on bone.

Male sex hormones play a critical role in regulation of bone metabolism. In male mice lacking androgen receptor (AR), osteopenia and high turnover state in bone remodeling have been reported. However, androgen receptor's role in disuse-induced osteopenia is not known. Therefore, we examined the effects of AR deficiency on unloading-induced bone loss. Wild type or androgen receptor deficient mice (ARKO) were subjected to hind limb unloading (HU) or normal housing (Control). The groups of mice were as follows; wild type control mice (Group WT-Cont), ARKO control mice (Group ARKO-Cont), wild type HU mice (Group WT-HU), and ARKO-HU mice (Group ARKO-HU). HU reduced cancellous bone mass in ARKO (ARKO-HU) by about 70% compared to ARKO-Cont and this reduction rate was over two-fold more than that of wild type (WT-HU) (reduction by less than 30% compared to WT-Cont). Combination of ARKO and HU (ARKO-HU) resulted in the least levels of cortical bone mass and bone mineral density among the four groups. ARKO-HU group indicated the highest levels of systemic bone resorption marker, deoxypyridinoline. Osteoclast development levels in the cultures in ARKO-HU derived bone marrow cells were the highest among the four groups. These data suggest that combination of androgen receptor deficiency and hind limb unloading results in exacerbation of disuse-induced osteopenia due to the enhanced levels of bone resorption.

[Clinical evaluation for radiotherapy of metastatic brain tumors in lung cancer: prognostic analyses relevant to QOL].

From 1986 through 1992, 144 patients with metastatic brain tumors of lung cancer were treated with X-ray irradiation to whole brain or a comparatively wide field of the brain. To identify the subset of patients indicated for boost therapy like a stereotactic radiotherapy, we have analyzed the treatment results concerning both survival and performance status (PS). Median survival time of the patients in good PS (0-2) was 6.7 months, which was significantly better than 2.3 months in poor PS (3-4). Complete tumor-resectability, age, steroid therapy and condition within two months after the beginning of brain irradiation, seemed to be important prognostic indicators correlated with PS by both univariate and multivariates analyses.

[Pharmacokinetic and clinical studies on cefmenoxime in neonates and infants].

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)

[Pharmacokinetics in neonates and infants following administration of amikacin].

Sixteen neonates (at ages of 8 to 28 days) and 8 infants (at ages of 35 days to 1 year), who were in need of treatment with amikacin sulfate, were subjected to the present study. The drug was administered by intramuscular route (1.39 to 3.13 mg/kg) or by intravenous drip infusion over a 30 to 60 minutes period (2.94 to 6.00 mg/kg). Blood levels and urinary excretion of the drug were investigated with these subjects. The blood levels were also analyzed according to pharmacokinetic models. 1. When the drug was administered intramuscularly to neonates at average doses of 1.49 and 2.96 mg/kg and to infants at average doses of 2.97 mg/kg peak levels of 2.74, 6.53 and 8.55 micrograms/ml, respectively, were attained at 30 minutes after dosing. 2. When the drug was administered to neonates at average doses of 3.01 and 5.89 mg/kg by intravenous drip infusion over a 30 to 60 minutes period and to infants at average doses of 2.97 and 6.00 mg/kg in the same manner, peak levels of 7.70, 20.9, 9.40 and 23.0 micrograms/ml, respectively, were attained at the end of the intravenous drip infusion. 3. Urinary levels and recovery rates tended to increase with ages of these subjects. Urinary recovery rates for the neonates and the infants were 41.0 and 58.9%, respectively, on the average. 4. From a pharmacokinetic analysis of blood levels of the drug, it was concluded that, in any of the subjects who received the drug intramuscularly or by intravenous drip infusion, it would be possible to use the one-compartment open model. In the subjects who received the drug by intravenous drip infusion, however, it was determined the two-compartment open model would be the choice. 5. In the neonates and the infants, whose blood levels were analyzed according to the one-compartment open model, Ka values averaged 7.51 and 6.62 hr-1, respectively, with respective average Kel values of 0.32 and 0.66 hr-1. Average Vd values obtained were 0.36 and 0.26 L/kg, respectively. There was a negative correlation between the Vd values and the ages of the subjects, while there was a positive correlation between the Kel values and the ages. 6. Appropriate conditions for administering the drug by intravenous drip infusion to neonates and infants at ages of more than 1 week were investigated taking observed blood levels and achieved peak levels and trough levels calculated using the one-compartment open model into account.(ABSTRACT TRUNCATED AT 400 WORDS)

[Study on the use of cefotiam in neonates].

Pharmacokinetic and clinical studies were carried out regarding the use of cefotiam (CTM) in the treatment of infections in newborn infants. Absorption and excretion: CTM was administered by bolus intravenous injection at a dose of 20 mg/kg to 9 newborns ranging in age from 1 to 28 days (gestational age, 34-40 weeks; birth weight, 2,000-3,380 g) and 6 infants aged 30 to 87 days (gestational age, 33 approximately 40 weeks; birth weight, 2,100-3,600 g) and its serum concentration and urinary excretion were determined. In the newborns, mean serum concentrations were 43.3 micrograms/ml at 1/4 hour, 36.7 microgram/ml at 1/2 hour, 27.8 micrograms/ml at 1 hour, 17.7 micrograms/ml at 2 hours, 8.8 micrograms/ml at 4 hours and 4.8 micrograms/ml at 6 hours, and in the infants, they were 44.5 micrograms/ml, 31.2 micrograms/ml, 19.1 micrograms/ml, 7.6 micrograms/ml, 2.2 micrograms/ml and 0.7 micrograms/ml at the above sampling times, respectively. Mean half-lives were 1.92 hours for the newborns and 0.96 hour for the infants, and mean urinary recoveries within 6 hours were 41.2% and 50.1% for the newborns and the infants, respectively. Taking individual differences into account, serum peak levels (at 1/4 hour) in newborns were very similar to each other irrespective of age (days after birth), and did not appear to be greatly different from those in infants. Half-lives, however, became shorter with aging, and the half-life of the serum CTM level in infants of about 1 month old should be close to those in young children or school-age children. From these observations, it is suggested to establish a standard regimen in which CTM is administered at a dose of 20 mg/kg once or twice a day to newborns within 3 days after birth, twice or 3 times a day to those aged 4 to 7 days, and 3 or 4 times a day to those aged 8 days or older. Clinical study: The CTM was administered to 11 patients with acute pneumonia, 2 patients each with suspected septicemia and with bullous impetigo, 1 patient with purulent lymphadenitis, 3 patients with idiopathic respiratory distress syndrome and 1 patient with pneumothorax, and its clinical effect was investigated. Excellent responses were observed in 12 of the 15 evaluated cases,good responses in 2, and a poor response in 1, thus an overall clinical effectiveness was 93.3%.(ABSTRACT TRUNCATED AT 400 WORDS)

[Fundamental and clinical evaluations of ceftazidime in neonates].

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 cefixime in pediatrics].

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 on aztreonam in the pediatric field].

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.

[Clinical studies of ceftizoxime suppositories in respiratory tract infections and urinary tract infections in children].

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 studies on aspoxicillin in the pediatric field].

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 on cefminox in the field of pediatrics].

A new antibiotic of cephamycin group, cefminox (CMNX, MT-141) was studied both fundamentally and clinically in the field of pediatrics. The minimum inhibitory concentrations (MIC) of CMNX for clinical isolates including 24 strains of S. aureus, 15 strains of S. pyogenes, 21 strains of H. influenzae, 24 strains of E. coli, 22 strains of K. pneumoniae and 22 strains of P. mirabilis were determined and compared to those of cefmetazole (CMZ), latamoxef (LMOX), cefotaxime (CTX), cefoperazone (CPZ) and cefazolin (CEZ). The MIC80 (80% MIC) values of CMNX for H. influenzae, E. coli, K. pneumoniae and P. mirabilis were 1.56, 1.56, 0.39 and 1.56 micrograms/ml, respectively. When compared to antibacterial activities of the control drugs, the activity of CMNX was inferior to those of CTX and LMOX but superior to those of CMZ and CEZ. On the other hand, MIC80 values of CMNX for S. pyogenes and S. aureus were 6.25 and 12.5 micrograms/ml, the activities being inferior to all of CMZ, CTX, LMOX, CPZ and CEZ used as the control drugs. In 3 pediatric patients of 9 to 12 years old, 20 mg/kg of CMNX was given intravenously as one shot and serum and urinary concentrations were determined. The mean serum concentrations in these 3 cases were 124 micrograms/ml, 102 micrograms/ml, 74.0 micrograms/ml, 47.9 micrograms/ml, 20.4 micrograms/ml, 9.2 micrograms/ml and 4.3 micrograms/ml at 1/4, 1/2, 1, 2, 4, 6 and 8 hours, respectively, with a half-life of 1.83 hours. The mean urinary concentrations were 1,968 micrograms/ml at 0 approximately 2 hours, 1,205 micrograms/ml at 2 approximately 4 hours, 761 micrograms/ml at 4 approximately 6 hours and 409 micrograms/ml at 6 approximately 8 hours, with 65.4% of the drug dosed recovered from the urine within the first 8 hours on an average. CMNX was used in the treatment of 22 clinical cases including 3 cases of acute purulent tonsillitis, 3 cases of acute bronchitis, 9 cases of acute pneumonia, 5 cases of acute pyelonephritis and 2 cases of acute enteritis. Clinical results in 20 cases excluded of 2 cases of Mycoplasma pneumonia were rated as excellent in 19 cases and as good in 1 case, with an efficacy rate being 100% taking excellent and good cases as effective cases. Bacteriological results for 5 strains of H. influenzae, 1 strain of H. parainfluenzae, 5 strains of E. coli, 2 strains of K. oxytoca and 1 strain of S. pneumoniae revealed that disappearance was obtained for all strains but 1 strain of P. aeruginosa which persisted.(ABSTRACT TRUNCATED AT 400 WORDS)

[Experimental and clinical studies on BRL 25000 (clavulanic acid-amoxicillin) in the pediatric field].

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)

[Fundamental and clinical evaluation of ceftriaxone in the pediatric field].

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)

[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)

[Fundamental and clinical studies on ceftazidime in the field of pediatrics].

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)

[Evaluation of latamoxef in neonates].

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)

[Experimental and clinical evaluation of cefpiramide in pediatrics].

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.

[Pharmacological evaluation of an ampicillin suppository (KS-R1) in acute pneumonia in children--a comparison with a parenteral preparation of ampicillin].

A comparative well-controlled study was performed to evaluate the efficacy and tolerability of KS-R1 (ampicillin (ABPC) rectal suppository) compared with those of intravenous injection of ABPC against acute bacterial pneumonia caused by ABPC-sensitive bacteria, such as Streptococcus pyogenes, Streptococcus pneumoniae and Haemophilus influenzae in pediatric field. KS-R1 at the dose of 250 mg X 4/day of ABPC in potency, or the intravenous injection at the dose of 125 mg X 4/day of ABPC in potency, was given to 68 cases of patients with bacterial pneumonia, aged between 10 months and 8 years and 2 months, for 7 days, as a rule. The clinical efficacy rates evaluated in 61 cases (KS-R1 group in 31 cases, intravenous group in 30 cases) on standard criteria of committee members were 93.5% for the KS-R1 group and 83.3% for the intravenous group, respectively. There was no significant difference between 2 groups. Evaluation by stratification according to the age showed that KS-R1 was significantly superior, the rate being 90.5% among the children from 1 year to 3 years in the KS-R1 group and 61.5% in the intravenous group. The bacteriological effect was evaluated in 16 cases (KS-R1 group in 7 cases, intravenous group in 9 cases), the disappearance rate was 100% for the KS-R1 group and 88.9% for the intravenous group, without significant difference. With regard to side effects, 66 cases (KS-R1 group in 35 cases, intravenous group in 31 cases) were strictly evaluated in relation to subjective and objective symptoms. As a result, no significant difference was noted between 2 groups in the incidence rate which was 17.1% for the KS-R1 group and 9.7% for the intravenous group. The above results indicate that against acute bacterial pneumonia in pediatric field, the KS-R1 at the dose of 250 mg X 4/day of ABPC in potency possesses clinical efficacy and safety similar to the intravenous injection at the dose of 125 mg X 4/day of ABPC in potency, and that it is a useful suppository.