Fundamental and clinical studies of ceftazidime in the pediatric field

Ceftazidime ( CAZ ), a newly-developed parenteral cephem antibiotic, was administered to 8 children; by one shot intravenous (i.v.) injection in the doses of 20 and 40 mg/kg each to 2 children, and by 30 minutes' i.v. drip infusion in the doses of 10 and 20 mg/kg each to 2 children, and the serum levels, urinary levels and recovery rates were determined. CAZ was also administered to 2 patients with purulent meningitis, one complicated with subdural abscess and the other with bacteremia, in the doses of 19.2 and 50.7 mg/kg, respectively, by one shot i.v. injection, and the CSF level of CAZ was determined. In addition, CAZ was administered to 2 children with acute bronchitis, 1 with chronic bronchitis, 37 with pneumonia, 3 with pleuropneumonia, 1 each for purulent meningitis, purulent meningitis accompanied with subdural abscess and purulent meningitis with bacteremia, 5 with urinary tract infections and 3 with purulent lymphadenitis (total 54 children), in the mean dose of 85.8 mg/kg/day mostly in 4 divided doses by one shot i.v. injection for 9 days on the average, and clinical effectiveness and bacteriological response were evaluated in these cases, and adverse events and abnormal laboratory findings were examined in the 66 cases which included 12 drop-out cases. 1. After the administration of CAZ to 4 children; 20 and 40 mg/kg each to 2 children, by one shot i.v. injection, the mean serum levels got to the peak of 115.8 and 199.5 mcg/ml, respectively, at 5 minutes. The results were good, showing dose response. The mean half-lives were 1.48 and 1.37 hours, respectively. After the administration of 10 and 20 mg/kg of CAZ each to 2 children by 30 minutes' i.v. drip infusion, the mean serum levels got to the peak of 58.5 and 80.0 mcg/ml, respectively, on completion of the administration, showing dose response. The mean half-lives were 1.06 hours in the former 2 cases, and 1.38 and 3.26 hours, respectively, in the latter 2 cases. The reason for the prolongation observed in 1 case was not clear. 2. In the above mentioned each 2 cases receiving one i.v. injection, the mean urinary levels got to the peak of 4,240 and 4,445 mcg/ml, respectively, at 0-2 hours after the administration , and the urinary recovery rates during the first 6 hours were high, 95.7% and 99.5%, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)     

Fundamental and clinical studies on ceftazidime

Ceftazidime ( CAZ ) was evaluated for its pharmacokinetics and clinical effects in the treatment of obstetrical and gynecological infections. The following results were obtained: Transfer of CAZ into various parts in the uterus and the uterine adnexa was found to be satisfactory, and relatively high concentration of the drug was maintained in the pelvic dead space exudate. Infections in the obstetrics and gynecology: 2 approximately 4 g of CAZ was given to 12 patients for 4 approximately 11 days and satisfactory clinical effect was obtained in 9 patients. There was a slight GOT elevation in 1 case but no other appreciable side effect or abnormal laboratory value was observed.     

Fundamental and clinical studies on ceftazidime in the perinatal period

Fundamental and clinical studies were carried out on ceftazidime (CAZ) in the perinatal period, and the results obtained were summarized below. Following bolus intravenous injection of CAZ 2 g, maternal serum concentrations of CAZ were as high as 145.3 +/- 17.2 micrograms/ml (mean +/- S.D.) at about 10 minutes, and then gradually decreased to 46.7 micrograms/ml at 2 hours, 5.31 micrograms/ml at 5 hours and 4 minutes, and 1.54 micrograms/ml at 11 hours and 10 minutes. The CAZ was detected in umbilical cord serum immediately after the administration, and concentrations were 31.0 +/- 1.54 micrograms/ml at about 10 minutes. Although the concentrations gradually decreased thereafter, they were higher than those in maternal serum at 3 hours and later and was 3.00 micrograms/ml at 11 hours and 10 minutes. The CAZ was detected in amniotic fluid a little later than in umbilical cord serum, and concentrations of CAZ in amniotic fluid were as low as 1.50 +/- 0.67 micrograms/ml at about 10 minutes after the administration. Concentrations then gradually increased to 12.8 micrograms/ml at 2 hours and 26.5 micrograms/ml at 5 hours and 4 minutes, and even at 11 hours and 10 minutes, they were as high as 14.2 micrograms/ml. The above results demonstrated that the transfer of CAZ through placental barrier was very rapid and satisfactory. Also, CAZ showed good transfer into amniotic fluid, as well as sufficient retention, and was considered to be an effective antibiotic for prophylaxis of both fetal infections and amniotic fluid infections.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fundamental and clinical evaluation of ceftazidime in perinatal studies

In a chemotherapy of perinatal infections, the safety of mothers and their neonates and the transfer of a drug to amniotic fluid and fetus as well as its bacteriological efficacy are some of the important factors. In the present study, the authors have carried out a pharmacokinetic evaluation on the transfer of ceftazidime (CAZ), a new cephalosporin, to amniotic fluid and umbilical cord serum, and also a clinical study on its efficacy and safety in 3 cases of perinatal infections. Transfer ratios of CAZ to umbilical serum and to amniotic fluid were 25.3-46.5% and 0.6-17.5% (of maternal serum), respectively, after 1 g of CAZ was administered by bolus intravenous injection, and 24.3-85.8% and 1.6-17.5% (of maternal serum), respectively, after 2 g of CAZ was administered by bolus intravenous injection. These levels were high enough to expect that CAZ is an effective antibiotic both for treatment and prophylaxis of intrauterine fetal infections. Out of the 3 cases treated with CAZ, clinical efficacy was good in 2 cases which did not respond to other antibiotics. CAZ was considered to be clinically effective, although the number of cases treated was small. No abnormalities were observed at all either in subjective symptoms or objective findings in laboratory findings such as hepatic and renal functions of mothers, or neonates. This confirmed the high safety of CAZ. As earlier reports indicate, CAZ has a broad-spectrum of antibacterial activity against various bacteria including Gram-negative organisms and anaerobes, and shows a good transfer into intrauterine tissues, and high clinical efficacy in the field of obstetrics and gynecology.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fundamental and clinical studies on ceftazidime in neonates and premature infants

Ceftazidime (CAZ) was administered to 34 full-term and premature infants aged 0-27 days with various bacterial infections in a dose of 10 or 20 mg/kg by intravenous bolus injection, and plasma concentrations and urinary recovery rates in these subjects during recovery periods were studied. Because of the small number of the cases recruited, neonates were not divided into the full-term and the premature group, but into 3 groups based on day-age: 0-3 days, 4-7 days, and 8 days or older. Concentrations and rates of transfer of CAZ into cerebrospinal fluid (CSF) were determined in 2 cases, and biliary concentrations in another case. A clinical evaluation of CAZ was performed in 12 male and 6 female infants aged 1 day to 4 months and 19 days, including 2 each with purulent meningitis, pneumonia and pyelonephritis, 3 with septicemia, 1 each with septicemia suspected, cholangitis, osteomyelitis, bronchopneumonia, staphylococcal scaled skin syndrome, and acute enterocolitis and 3 for prophylactic use. Plasma concentrations and urinary recovery rates of CAZ The intravenous bolus injection at 10 mg/kg. Peak plasma concentrations of CAZ were obtained at the first collection (30 minutes) of blood samples or 1 hour in all 3 groups, ranging from 23.3 to 26.9 micrograms/ml with no significant variations, plasma concentrations then slowly decreased, and were still 6.04-9.88 micrograms/ml even at 6 hours after the administration. The half-lives of CAZ in plasma tended to be shorter in older day-age neonates, with mean half-lives being 3.59, 2.50 and 2.50 hours for the youngest. The intravenous bolus injection at 20 mg/kg. Peak concentrations were obtained at the first collection of blood samples in all 3 groups (0-3 days: 15 minutes, the others: 30 minutes), being 54.8, 39.9 and 43.8 micrograms/ml, respectively, then slowly decreased and were still 10.4-15.7 micrograms/ml even at 6 hours after the administration. Inter-age differences in half-lives were marked, i.e., 3.6 hours in 0-3-day group, 3.48 hours in 4-7-day group and 2.75 hours in 8-day or older group. Urinary recovery rates were about 40-60% without reference to day-age neonates. CSF concentrations About 50 mg/kg of CAZ was given to each of 2 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)     

Basic and clinical studies on ceftazidime in the pediatric field

Basic and clinical studies were made on ceftazidime (CAZ) in pediatric field, and the following results were obtained. The antibacterial activity of CAZ against clinically isolated and maintained strains was examined. CAZ was unequivocally more active than CEZ and CMZ against Gram-negative rods, with MIC distribution similar to that of CTX, except for that for P. aeruginosa. The MIC of CAZ was lower than that of CTX for P. aeruginosa. Compared with the MICs of CEZ, CMZ and CTX, CAZ showed slightly higher MICs for Gram-positive bacteria. The blood concentrations of CAZ, at 0.25, 0.5, 1, 2, 4 and 6 hours after a one shot intravenous injection of 10 mg/kg of CAZ were 64.9, 36.9, 28.3, 14.7, 4.92 and 2.42 micrograms/ml, respectively, with the half-life of 1.27 hours. The blood concentrations of CAZ, at 0.25, 0.5, 1, 2, 4 and 6 hours after a 1-hour drip infusion of 10 mg/kg of CAZ were 16.6, 24.5, 41.4, 17.1, 5.38 and 2.62 micrograms/ml, respectively, with the half-life of 1.28 hours. The blood concentrations of CAZ, at 0.25, 0.5, 1, 2, 4 and 6 hours after a one shot intravenous injection of 20 mg/kg of CAZ were 73.1, 60.8, 39.3, 17.3, 8.23 and 4.45 micrograms/ml, respectively, with the half-life of 1.42 hours. The blood concentrations of CAZ, at 0.5, 1, 2, 4 and 6 hours after a 1-hour drip infusion of 20 mg/kg of CAZ were 55.1, 69.0, 32.1, 11.4 and 4.56 micrograms/ml, respectively, with the half-life of 1.27 hours. Urinary recovery rate of CAZ during the first 6 hours after a one shot intravenous injection of 10 mg/kg of CAZ was 86.7%. CAZ was administered to 17 children with infections, and the clinical response was excellent or good in 94%. CAZ was bacteriologically effective in 14 patients, all bacteria having been eradicated in them. The bacteria were E. coli in 10 patients, H. influenzae in 2, P. aeruginosa in 1 and S. pneumoniae in 1. As for side effects, slight elevation in GOT was observed in 1 case and eosinophilia, in another case.     

Fundamental and clinical studies of ceftazidime in the field of pediatrics

We have studied ceftazidime (CAZ), a cephem antibiotic of the new generation, for its antibacterial activity against H. influenzae and clinical effects. Antibacterial activity: MICs of CAZ for 142 strains of H. influenzae including 11 ABPC-resistant strains which were clinically isolated, were determined, and the results were good for all the strains. Clinical effects: CAZ was administered to 9 children with infections. Suspected causative organisms were H. influenzae, E. coli, P. aeruginosa, group B Streptococcus and S. pneumoniae. Eradication of these organisms was confirmed in all the strains except for one in which the antibacterial effect of CAZ was unknown. Clinical efficacy was excellent or good in all the cases. No side effect was observed except for eosinophilia noted in 1 case.     

Fundamental and clinical studies on ceftazidime in the field of obstetrics and gynecology

Fundamental and clinical studies were performed on ceftazidime ( CAZ ), a new cephem antibiotic. Following a single intravenous administration of 1 g dose of CAZ , the transfer of CAZ to the internal genital organs was good. The transfer of CAZ to retroperitoneal fluid was excellent. In a clinical trial, CAZ was given to 6 patients with obstetrical and gynecological infections. The efficacy was evaluated as excellent in 3 cases and good in the other 3 cases. No adverse effects were observed in any of the patients treated with CAZ .     

Fundamental and clinical studies on cefixime in pediatric field

Cefixime (CFIX) was evaluated for pharmacokinetics, therapeutic effectiveness on infection, safety, and bacteriological effectiveness in pediatrics. The following is a summary of the results. Pharmacokinetics in 4 children, 2 each receiving a single dose of 1.5 mg or 6.0 mg per kg body weight, were examined. Peak serum CFIX concentrations after the dose of 1.5 mg/kg were 1.12 and 1.34 micrograms/ml, and the serum half-lives were 1.83 and 3.53 hours. For the children administered with 6.0 mg/kg of CFIX, the respective figures were 2.50 and 7.46 micrograms/ml, and 6.77 and 6.64 hours. The 12-hour urinary recoveries were 4.9 and 34.1% and 9.4 and 25.4% for the small and the large doses, respectively. Therapeutic effectiveness in 19 children with infections was "excellent" in 14 and "good" in 5, with an effectiveness rate of 100%. Bacteriological effectiveness was evaluated in 10 children. Classified by causative organisms, 5 cases had H. influenzae, 2 each H. parainfluenzae and S. pyogenes, and 1 mixed infection by H. influenzae and S. pneumoniae. Only the H. influenzae in the child with mixed infection resisted the therapy, and all the other pathogens were successfully eradicated. No side effects were recorded. The only abnormal laboratory test finding attributed to CFIX was eosinophilia in 2 children.     

Laboratory and clinical studies of ceftazidime in the pediatric field

The authors have carried out the laboratory and clinical studies of ceftazidime ( CAZ ) and obtained the following results. The antibacterial activities of CAZ against the clinical isolates of S. aureus, E. coli, K. pneumoniae, E. cloacae, E. aerogenes, S. marcescens, C. freundii and P. aeruginosa were measured by the plate dilution method with inoculum size of 10(6) cells/ml. The susceptibility distribution of S. aureus to CAZ ranged from 3.13 to 100 micrograms/ml, and the peak of distribution was 12.5 micrograms/ml. The peak of susceptibility distribution of E. coli, K. pneumoniae and E. cloacae was 0.2 micrograms/ml, and the distribution of E. aerogenes ranged from 0.1 to 100 micrograms/ml and that of S. marcescens, from 0.05 to 3.13 micrograms /ml. The growth of 92% of P. aeruginosa was inhibited at the concentration of 3.13 micrograms/ml or lower. For pharmacokinetic study, CAZ was given in a single dose of 10 mg/kg by intravenous administration for 5 minutes in 1 child and by drip infusion for 30 minutes in 2 children. After intravenous administration of CAZ , the serum level got to the peak of 41.0 micrograms/ml at 15 minutes, and was 1.0 micrograms /ml at 6 hours. Half-life time was 1.30 hours. With drip infusion of CAZ , the mean peak serum level was 52.45 +/- 2.05 micrograms/ml on completion of the infusion, and 1.05 +/- 0.05 micrograms/ml at 6 hours. Half-life time was 1.30 hours. CAZ was effective in 9 cases out of 11 cases with bacterial infection. No side effect was observed except for elevation of serum GOT and GPT in 1 case and eosinophilia in 1 case.     

Fundamental and clinical studies on cefixime in the pediatric field

Fundamental and clinical studies on cefixime (CFIX), a new oral cephem antibiotic, were carried out in the pediatric field. The results were as follows: Serum concentrations and urinary recovery rates were determined after oral administration of CFIX at doses of 3 mg/kg and 6 mg/kg in 2 cases each (4 cases in total). The mean serum concentrations of CFIX were 0.52 and 0.58 micrograms/ml at 2 hours, 0.80 and 1.42 micrograms/ml at 4 hours, 0.73 and 1.36 micrograms/ml at 6 hours, 0.54 and 1.12 micrograms/ml at 8 hours, respectively. The mean peak serum concentration of CFIX was obtained at 4 hours after administration, with serum half-lives (T1/2) of 3.77 and 5.30 hours, respectively. The mean cumulative urinary recovery rates within 12 hours after administration of CFIX at doses of 3 mg/kg and 6 mg/kg were 8.4% and 6.8%, respectively. Antibacterial activities of CFIX against clinically isolated strains of S. pyogenes, S. pneumoniae. E. faecalis, S. aureus, E. coli, H. influenzae, H. parainfluenzae were compared with those of amoxicillin (AMPC), cefaclor (CCL), and cephalexin (CEX). It was observed that CFIX was a little less active than AMPC against S. pyogenes and S. pneumoniae, but CFIX was more active than CCL and CEX. CFIX was the most active against E. coli, H. influenzae and H. parainfluenzae. Twenty-one pediatric patients with bacterial infections (10, tonsillitis; 4, pharyngitis; and 7, urinary tract infections) were treated with CFIX at doses of 1.5-6.0 mg/kg in 2 or 3 times daily for 4-10 days. The efficacy rate was 95.2% clinically and 91.3% bacteriologically. No adverse reactions were observed. An abnormal laboratory finding (slight elevation of S-GOT and S-GPT) was observed in 1 case.     

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 cefuzoname in the pediatric field

Cefuzoname (CZON) one of the aminothiazolyloxyiminoacetamido cephalosporins, was studied for its antibacterial activity, absorption and excretion, concentration in the cerebrospinal fluid (CSF) and the penetration, and clinical efficacy. The following are a summary of the results: 1. Antibacterial activity; The antibacterial activity of CZON was studied on clinically isolated Staphylococcus aureus (cefazolin (CEZ)-susceptible and CEZ-tolerant strains), Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis. Compared with CZON were cefmenoxime (CMX), latamoxef (LMOX), cefoperazone, cefmetazol (CMZ), cefotiam and CEZ, but for S. aureus cefamandole (CMD) was replaced for CPZ. Activities of CZON against S. aureus, both CEZ-susceptible and CEZ-tolerant strains, were superior to those of 6 control drugs. The distribution of MICs for the CEZ-susceptible strains was 0.10-12.5 micrograms/ml, and for the CEZ-tolerant strains 0.20-greater than 100 micrograms/ml. MIC peaks were 0.39 micrograms/ml and 0.78-1.56 micrograms/ml for CEZ-susceptible and CEZ-tolerant strains, respectively. Against both susceptible and tolerant strains, CZON showed superiority to CMZ and CMD, which are used prevalently and used for Methicillin-resistant S. aureus also. Distributions of MICs of CZON (and the peak of MICs) on E. coli, K. pneumoniae, and P. mirabilis were less than or equal to 0.025-1.56 (less than or equal to 0.025), less than or equal to 0.025-25 (less than or equal to 0.025-0.05), less than or equal to 0.025-25 (less than or equal to 0.025) micrograms/ml, respectively, showing CZON's similar antibacterial activity to those of cephalosporins, CMX and LMOX, which are 5th group. 2. Absorption and excretion: Eight patients, aged 10 months to 15 years, were administered with CZON 20 mg/kg, one shot intravenously. Serum concentrations somewhat varied from patient to patient, but the mean value was 48.7 micrograms/ml after 30 minutes of administration which decreased rapidly to 13.3 micrograms/ml after 1 hour, to 3.4 micrograms/ml after 2 hours, to 1.14 micrograms/ml after 4 hours, and to 0.15 microgram/ml after 6 hours. Half-lives were 0.67-1.47 hours, with the mean of 0.87 hour. Urinary recovery rates were 24.7-55.9%, with the mean of 45.1%, in 6 hours after administration. 3. CSF concentration and penetration rate: To 4 pediatric patients with purulent meningitis, CZON 25 mg/kg or 50 mg/kg was administered and the concentration in CSF was measured.(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.     

Fundamental and clinical studies of ceftazidime in the field of obstetrics and gynecology

Ceftazidime ( CAZ ), a new cephalosporin antibiotic, was fundamentally and clinically studied. The following results were obtained. Serum and internal genital tissue levels of CAZ were measured following intravenous drip infusion of 1 g for 30 minutes. Serum levels of more than 10 micrograms/ml and tissue levels of more than about 7 micrograms/ml were maintained after 2 hours to 2 hours and 30 minutes, respectively. Favourable transfer of CAZ into the pelvic dead space exudate was observed. The exudate level attained its peak of 31.54 micrograms/ml on average at 2 hours and was 16.8 micrograms/ml on average even at 8 hours after intravenous drip infusion. A total of 6 cases comprising 1 of adnexitis, 2 of pyometra, 1 of endometritis and 2 of parametritis was treated with CAZ at a dose of 0.5 approximately 2.0 g twice daily by intravenous injection or intravenous drip infusion. The clinical response was excellent in 1 case, good in 4 cases and poor in 1 case. Abnormal laboratory findings and side effects due to the drug were not noted.     

Fundamental and clinical studies of aztreonam in pediatric infections

Fundamental and clinical studies were carried out with aztreonam (AZT), a new monocyclic beta-lactam antibiotic, in pediatric infections. Results were as follows. The mean half-lives in the vein blood were 1.09 hours, 1.18 hours, 1.22 hours after injection, when the doses were 10, 20 and 40 mg/kg, respectively. Dose response was observed. The average recovery rates in the urine between 0 and 6 hours were 40.2%, 42.3%, 50.8% when the doses were 10, 20 and 40 mg/kg, respectively. The antibacterial activity of AZT against 16 clinical isolates were determined in comparison with those of ABPC, CPZ, LMOX and CTX. Against 8 clinical isolates of E. coli and 3 of H. influenzae, the activity of AZT was equal or superior to that of CPZ, LMOX and CTX, and way by far superior to that of ABPC. Twenty-three pediatric patients received AZT in doses ranging from 48 to 79 mg/kg divided 3 times a day; 12 cases of urinary tract infection, 9 cases of respiratory tract infection and 2 cases of bacterial enterocolitis. The rate of clinical effectiveness was 100%. No side effect was observed. Slight elevation of GOT and GPT were observed in 2 cases, increase of platelet count in 2. All were considered to be transient and mild.     

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.     

Clinical studies on ceftazidime in the pediatric field

Ceftazidime ( CAZ ) is a newly developed cephalosporin. Clinical studies on this drug was carried out and the results were as follows. Twenty-nine patients (acute purulent tonsillitis 2, acute bronchitis 1, pneumonia 15, acute purulent lymphadenitis 2, pyoderma 1, skin abscess 2 and urinary tract infection 6) were treated with CAZ in doses of 42-1 mg/kg (mean 59 mg/kg) divided 2-3 times per day for 3-10 days (mean 5.7 days) intravenously. The overall efficacy rate was 96.6%. As to adverse reaction, drug fever was observed in 1 patient. Abnormal laboratory data were noted in 4 cases (elevation of serum GOT, GPT and BUN in 1, elevation of serum GOT and GPT in 1, elevation of BUN in 1 and leukopenia in 1).     

Fundamental and clinical studies of aspoxicillin in the pediatric field

Aspoxicillin (ASPC), a new semisynthesized penicillin, was administered to 20 children; by one shot intravenous injection in the doses of 10, 20 and 40 mg/kg to each of 3 children, and by intravenous drip infusion in the doses of 20 and 40 mg/kg over a period of 1 hour to 8 and 3 children, respectively, and the serum levels, urinary levels and recovery rates were determined. ASPC was administered to 1 patient with tuberculous pleurisy in the dose of 20 mg/kg by one shot intravenous injection, then the thoracic fluid level and serum level were determined. In addition, ASPC was administered to 3 children with tonsillitis, 3 with bronchitis, 40 with pneumonia, one each for pleuropneumonia, pleurisy, lung abscess, scarlet fever, staphylococcal scalded skin syndrome and purulent lymphadenitis and 2 with UTI (total 54 children), in the mean dose of 81.4 mg/kg/day t.i.d. (12 children) or q.i.d. (42 children) by one shot intravenous injection for 6 days on the average, and clinical effectiveness and bacteriological response were evaluated in these cases, and adverse reactions and abnormal laboratory findings were examined in the 60 cases which included 6 drop-out cases. After the administration of ASPC to 9 children; 10, 20 and 40 mg/kg to each of 3 children, by one shot intravenous injection, the mean serum levels reached to the peak of 58.4, 147.0 and 221.0 mcg/ml, respectively, in 5 minutes. The mean half-lives were 1.03, 1.01 and 1.23 hours, and the mean areas under the curve (AUCs) were 44.9, 94.1 and 192.9 mcg X hr/ml, respectively. A dose response was seen among the 3 dosage levels. After the administration of ASPC to 11 children; 20 and 40 mg/kg to 8 and 3 children, respectively, by intravenous drip infusion over a period of 1 hour, the mean serum levels reached to the peak of 58.2 and 114.0 mcg/ml, respectively, on completion of the administration. The mean half-lives were 1.22 and 1.09 hours, and the mean AUCs were 109.4 and 181.7 mcg X hr/ml, respectively. A dose response was observed between the 2 dosage levels. In the above mentioned each 3 cases receiving one shot intravenous injection in the dose of 10, 20 and 40 mg/kg, the mean urinary levels of ASPC reached to the peak of 1,000.0, 2,300.0 and 4,350.0 mcg/ml, respectively, at 0 approximately 2 hours after the administration, and the urinary recovery rates during the first 6 hours were 66.1, 66.5 and 56.9%, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)