Effects of ceftizoxime suppository rectal dosing on cecal microflora in mice

The effect of ceftizoxime suppository (CZX-S), a new rectal preparation of ceftizoxime (CZX), against cecal microflora of mice following consecutive rectal administration was compared with that after subcutaneous administration of CZX. The numbers of aerobic and anaerobic bacteria except Enterobacteriaceae of cecal microflora were not markedly changed by the rectal administration of CZX-S at a dose of 25 mg/kg 3 times daily for 10 days. Although the number of Enterobacteriaceae was decreased, recovery was rapidly observed after completion of the administration period. In the case of subcutaneous administration, a decrease in Enterobacteriaceae was also observed, but this was no more remarkable than that occurring with rectal administration. Moreover, effects on the state of feces, i.e., diarrhea, were not observed in any of the mice. The peak level of CZX in the cecum contents when administered rectally at a dose of 25 mg/kg was 13.8 micrograms/g at 4 hours, while it was less than the determination limit (2.0 micrograms/g) when administered subcutaneously at the same dose.     

Clinical study of ceftizoxime suppositories in acute suppurative otitis media in children and tissue concentration of ceftizoxime in the palatine tonsil after administration of ceftizoxime suppositories

The newly developed ceftizoxime rectal suppository (CZX-S) contains 125 mg or 250 mg ceftizoxime (CZX) in potency. From the laboratory and clinical studies on CZX-S, the following results were obtained. Concentration of CZX in serum and palatine tonsil when 250 mg of CZX-S was rectally administered reached the peak level rapidly. The serum levels were 9.39 micrograms/ml in 30 minutes, 6.00 micrograms/ml in 45 minutes, 4.55 micrograms/ml in 60 minutes, 3.87 micrograms/ml in 90 minutes and 2.65 micrograms/ml in 120 minutes. The palatine tonsil levels were 2.73 micrograms/g in 30 minutes, 1.83 micrograms/g in 45 minutes, 1.54 micrograms/g in 60 minutes, 0.99 micrograms/g in 90 minutes and 0.74 micrograms/g in 120 minutes. About 30% of serum concentrations were distributed into palatine tonsil. CZX-S was administered at a daily dose of 375 mg or 750 mg divided 3 times for 4 approximately 9 days in 19 cases of acute suppurative otitis media of children. The overall clinical effect was excellent in 7 cases, good in 7 cases, fair in 2 cases and poor in 3 cases. The effectiveness rate was 73.7%. No side effects were observed in any cases.     

Fundamental study on ceftizoxime suppositories in adults and children

The pharmacokinetics of newly developed ceftizoxime suppository (CZX-S) was studied in healthy volunteers and in children, compared with that of intramuscular CZX and intravenous CZX: In 8 volunteers (aged 19 to 24 years), each of 500 mg (potency) CZX-S containing 3%, 4% and 5% sodium caprate was compared with 500 mg intramuscular CZX and 500 mg intravenous CZX as a single administration in the cross-over method. In addition each of 500 mg CZX-S containing 4% and 5% sodium caprate was studied in 2 groups of 8 volunteers (aged 22 to 24 years) and of 8 volunteers (aged 19 to 27 years); each CZX-S was given 3 times a day successively for 5 days. The pharmacokinetics of 125 mg and 250 mg CZX-S, which contained 3% sodium caprate, were also evaluated as a single administration in 9 children (aged 6 years 4 months to 12 years 0 month) and in 11 children (aged 7 years 8 months to 12 years 4 months), respectively. The irritabilities of CZX-S were studied in all subjects who participated in this trial. The feeling of foreign body, the feeling of defecation, the burning sensation and the pain were evaluated in volunteers; the feeling of defecation and the pain were evaluated in children. The results were as follows: I. Pharmacokinetics in healthy volunteers 1. Given as a single administration The mean peak concentrations of serum CZX were occurred 30 minutes after 500 mg CZX-S containing 3%, 4% and 5% sodium caprate, which were 10.5 mcg/ml, 12.3 mcg/ml and 12.4 mcg/ml, respectively. These values were 1.35 mcg/ml, 1.60 mcg/ml and 1.69 mcg/ml at the conversion unit of 1 mg dose per 1 kg body weight. The mean peak serum CZX concentration of CZX-S containing 3% sodium caprate was slightly lower than that of CZX-S containing 4% or 5% sodium caprate, but was 1.9 times higher than that of the ABPC suppository. There was no marked difference among 3 preparations of CZX-S in mean Tmax and T1/2. Cmax of CZX-S containing 3% sodium caprate was 1.40 mcg/ml at the conversion unit of 1 mg/kg. AUC of CZX-S containing 3% sodium caprate was slightly smaller than that of CZX-S containing 4% or 5% sodium caprate, but 3.1 times that of the ABPC suppository in healthy volunteers. When 500 mg CZX was intramuscularly administered by one shot to 8 volunteers, Tmax was same as that of CZX-S or was slightly later.(ABSTRACT TRUNCATED AT 400 WORDS)     

Clinical investigation of ceftizoxime sodium suppositories in the field of pediatrics

The clinical study of CZX-S in the field of pediatrics was performed and the following results were obtained. The overall effect of CZX-S was "markedly improved" in 2 and "moderately improved" in 4 of the 6 patients with bacterial infection. Bacteriological findings show that causative organisms were eradicated in all the 5 patients observed. The breakdown of the organisms was S. aureus, S. pyogenes, S. pneumoniae, H. influenzae and E. coli. The serum concentration of CZX was 3.3 approximately 15.4 micrograms/ml (mean +/- S.E. 8.9 +/- 2.0 micrograms/ml) at 15-37 minutes after initial rectal administration with CZX-S 125 (dose: 7.7-11.9 mg/kg). While, in the CZX-S 250 administratered group, the serum concentration was 3.1 micrograms/ml and 10.5 micrograms/ml at 20 minutes after initial rectal administration (dose: 5.6 mg/kg and 14.7 mg/kg). The urinary recovery rate up to 6 hours after initial rectal administration was 68.6% in 1 patient given CZX-S 125 and 28.3-52.5% (mean +/- S.E. 38.7 +/- 7.2%) in 3 patients given CZX-S 250. Side effects and abnormalities in laboratory test values were not observed in any cases.     

Study on tissue transfer of ceftizoxime suppository in the field of obstetrics and gynecology

A pharmacokinetic study on ceftizoxime suppository (CZX-S), a new rectal suppository of ceftizoxime (CZX), was carried out in the field of obstetrics and gynecology. Concentrations of CZX after single rectal administrations of a 500 mg dose in peripheral venous serum, uterine arterial serum and internal genital organs of 15 patients who received simple panhysterectomy were examined. Peak levels of CZX in peripheral venous serum were 7.26 to 8.88 micrograms/ml at 30 minutes after the administration. Concentrations of CZX in internal genital organs reached 2.12 to 8.96 micrograms/g at 30 minutes after the administration and then decreased slowly, but still remained at 0.37-3.12 micrograms/g after 4 hours.     

Fundamental and clinical studies of ceftizoxime rectal suppositories in the field of pediatrics

This paper deals with fundamental and clinical results, in the field of pediatrics, of the newly developed rectal suppository (CZX-S) of a cephem antibiotic ceftizoxime (CZX). CZX-S was well absorbed in children. The mean peak serum concentrations of CZX in the 125 mg-administered group (average: 9.9 mg/kg) and the 250 mg-administered group (average: 13.4 mg/kg) were 5.10-7.71 micrograms/ml at 15-30 minutes after dosing. Serum concentrations of CZX were measurable level in almost all the children at 6 hours after administration with the half-lives were 1.34-1.55 hours. The 6-hour urinary excretion rate accounted for 16.5-22.0%. CZX-S was administered to 30 children with acute upper or lower respiratory tract infections about 20-60 mg/kg/day in 3-4 divided portions. CZX-S provided favorable therapeutic-effect in most of the children 3-5 days after administration. The effectiveness rate was 93%. The causative organisms of H. influenzae (3 cases) and S. aureus (4 cases) isolated clinically from pharyngeal mucous and sputum were eradicated after administration of CZX-S. Anal pain and diarrhea experienced in 5 of the 30 children and CZX-S was withdrawn in 4 (of the 5) children, but exhibited satisfactory therapeutic-effect in 2 of the 4 cases up to withdrawal of the drug. An increase in GOT and GPT was observed in 3 cases. The values returned to the normal range in 1 case after the treatment with CZX-S. The test was not reexamined in the other 2 cases. The present clinical result suggests the usefulness of CZX-S substituted for oral and injectable forms in the treatment of various pediatric infections caused by organisms sensitive to CZX.     

Fundamental and clinical studies of ceftizoxime suppositories in the pediatric field

The fundamental and clinical studies of ceftizoxime suppository (CZX-S) in the field of pediatrics were made, with the following results. The serum concentration of CZX in the CZX-S 250 mg-administered group peaked 6.00-22.5 micrograms/ml during the period of 15 minutes to 1-hour after dosing, and gradually declined thereafter. The half-life was 1.37-3.81 hours. In the CZX-S 125 mg-administered group, the serum concentration peaked 2.25-21.0 micrograms/ml at 15-30 minutes after dosing and decreased with time. The half-life was 0.95--1.84 hours. The 6-hour urinary recovery rate of CZX in the CZX-S 250 mg group was 22.0-47.5%. The 6-hour urinary recovery rate in the CZX-S 125 mg group was 17.2-25.3%. CZX-S was given 12-73 mg/kg/day (divided into 1-3 times) to 7 children with respiratory tract infection etc. who were considered to respond well to the drug. The clinical effectiveness rate was 100% inclusive of "excellent" and "good". The side effect of pain on insertion was encountered in 1 child.     

Clinical and pharmacokinetic evaluations of ceftizoxime suppositories in children

Ceftizoxime suppository (CZX-S) was evaluated for its safety, clinical efficacy and pharmacokinetics in pediatric patients. The Cmax, 4.8 to 9.5 micrograms/ml, was obtained 15 to 30 minutes after administration of CZX-S, and the serum half-life was 0.93 hour. Cross-over comparison with intramuscular CZX in a child showed approximately one-third bioavailability of the suppository against intramuscular injection. CZX-S was effective in all the 26 bacterial infections including acute pharyngitis, pneumonia, soft tissue infection, and urinary tract infections. The causative organisms were eradicated in 95%. Mild diarrhea (17%) was the only side effect observed in the study. The data suggest that CZX-S is an excellent alternative to oral and injectable antibiotics for the treatment of mild to moderate bacterial infections due to the susceptible organisms.     

Fundamental and clinical studies on ceftizoxime suppositories in children

The peak levels of serum ceftizoxime (CZX) after a single rectal administration of CZX-S at doses of 125 and 250 mg in 157 pediatric patients were occurred at 21 approximately 25 minutes in pediatric patients aged less than 1 year and over than 7 years, at 16-20 minutes in 1-3 years patients, at more than 26 minutes in 4-6 years patients. They were 9.45, 9.58, 11.71, 12.43 mcg/ml, respectively. The mean highest levels of serum CZX were 8.56, 10.66, 12.50 mcg/ml after the administration of CZX-S as less than 10.0, 10.1-15.0, 15.1-20.0 mg/kg dose respectively, all of which were occurred at 21-25 25 minutes. A close dose response was observed. The pain of insertion was not observed in any cases. The discharge of melted suppository or defecation after administration was observed in 15.2% of total 184 cases, which was noticed more frequently in the lower aged children. There was no influence by dose. Clinical effects of CZX-S were studied in 72 pediatric patients with various infections. CZX-S was administered rectally at the mean daily dose of 41.0 mg/kg divided into 3 or 4 times for 6 days. Clinical responses were excellent in 46 cases, good in 24 cases, fair in 2 cases. The efficacy rate was 97.2%. Regarding side effects, the pain of insertion was noted in 2 cases (2.8%), diarrhea in 6 cases (8.3%), the elevation of eosinophil in 1 case (1.7%). Bacteriologically, 23 strains (92.0%) out of 25 strains isolated from the patients were eradicated.     

The clinical evaluation of ceftizoxime suppositories in the pediatric field

Clinical evaluation of ceftizoxime suppository (CZX-S), a new antibiotic rectal suppository, was performed in 5 cases with bacterial infections in pediatric field (2 with acute bronchitis, 1 with acute tonsillitis, UTI and pertussis, respectively) and the following results were obtained; Blood levels of CZX at 10-20 minutes after administration of CZX-S at a dose of 10.0-26.3 mg/kg in 5 cases were 3.26-23.3 micrograms/ml and the urinary excretion rates within 6 hours were 15.2, 60.1, 60.2% in 3 of 5 cases measured respectively. Clinical effects were excellent in 3 and good in 2 cases. Slight elevation of GOT and GPT was observed in 1 case. No other side effects were observed. The patients' tolerability against rectal suppository was good. From the above results, we concluded that CZX-S is useful for treating the pediatric patients with various infections.     

Fundamental and clinical studies of ceftizoxime suppositories in pediatrics

Fundamental and clinical studies were carried out on ceftizoxime suppository (CZX-S), and the following results were obtained in pediatrics. In 4 patients of the CZX-S 125 mg-administered group (9.4-9.9 mg/kg), the serum concentration of CZX reached a peak of 5.55 micrograms/ml on the average, 30 minutes after dosing, i.e. at the time of initial blood collection, and decreased gradually to 0.20 microgram/ml 6 hours after dosing. The half-life was 1.09 hours. In 5 patients of the CZX-S 250 mg-administered group (8.4-18.1 mg/kg), the serum concentration of CZX peaked at 7.07 micrograms/ml on the average and then gradually declined to 0.16 microgram/ml 6 hours after dosing. The half-life was 1.00 hour. The urinary recovery rate varied as widely as 6.5-38.0% in all the patients of both groups. CZX-S was given to total 19 patients; 8 patients with urinary tract infection (UTI), 3 with pharyngitis or tonsillitis, 4 with bronchitis, 2 with pneumonia, 1 with otitis media and 1 with staphylococcal scalding skin syndrome. The overall effect of CZX-S in 15 patients was "effective" or better response, with an effectiveness rate of 83.3%, except one who discontinued the drug because of side effects. CZX-S was given to most of the patients weighing 15 kg or higher in a dose of 250 mg 3-4 times a day and frequently to patients weighing less than 15 kg in a dose of 125 mg 3-4 times a day. As to side effects, slight diarrhea was encountered in 1 patient. Laboratory examinations disclosed an increase in GOT in 1 patient, which returned to normal after continual insertion of the suppository.     

L-656,575 (OCP-9-176): a novel oxacephem. Pharmacokinetics and experimental chemotherapy

L-656,575 is a new oxacephem that, based on studies in rhesus monkeys, is expected to have a moderately long half-life in humans. After administration of a 10-mg/kg dose by the intramuscular route to rhesus monkeys, peak serum concentrations of 32-54 micrograms/ml were seen at about 30 minutes, and the half-life was estimated to be 63 minutes. Urinary recovery of administered dose was greater than 94% in 6 hours. In mice given a 20-mg/kg dose by the subcutaneous route, a peak serum concentration of 22.9 microgram/ml was observed at 15 minutes after dosing, and the half-life in serum was about 18 minutes. Urinary recovery of the dose was 59% in 6 hours. In another study in mice, administration of probenecid did not extend the half-life of L-656,575, suggesting that the antibiotic is excreted primarily by glomerular filtration in this species. Binding to human plasma proteins was 30% at drug concentrations from 25-100 micrograms/ml. L-656,575 also was shown to be efficacious in experimental bacteremias due to Gram-positive and Gram-negative pathogens in mice, thus confirming the broad spectrum of activity demonstrated for L-656,575 in vitro.     

Pharmacokinetic and clinical studies on ceftizoxime in the perinatal period

Pharmacokinetic and clinical studies were carried out on the use of ceftizoxime (CZX) in the perinatal period. The results obtained are summarized below. 1. Mean maternal serum concentrations of CZX reached 57.3 micrograms/ml at about 15 minutes after a single intravenous injection of CZX 1 g and then gradually decreased to 13.1 micrograms/ml in 1 hour and 55 minutes, 3.59 micrograms/ml in 4 hours and 20 minutes and 0.11 microgram/ml in 17 hours and 51 minutes. CZX in umbilical cord serum was at detectable concentrations soon after administration and peaked to 23.5 micrograms/ml in 32 minutes. Although the concentrations in umbilical cord serum gradually decreased thereafter, they were higher than those in maternal serum at 3 hours and more after an injection and was 0.41 microgram/ml at 17 hours and 51 minutes. The CZX in amniotic fluid became detectable a little later than CZX in umbilical cord serum. The concentration of CZX in amniotic fluid was below 1.00 microgram/ml at 30 minutes after administration. Concentrations then gradually increased to 21.3 micrograms/ml in 1 hour and 55 minutes and, even in 17 hours and 51 minutes, they were as high as 9.44 micrograms/ml. 2. In the clinical evaluation, CZX was given to a total of 7 cases, i.e., 1 of amnionitis, 2 of puerperal endometritis, 1 of puerperal fever, and 3 of pyelonephritis. The treatment showed satisfactory results, i.e. excellent result was obtained in 1 case, good in 5 and poor in 1 with an clinical efficacy rate of 85.7%. Microbiological examinations resulted in the isolation of 5 bacterial strains of 4 species and 1 fungal strain from 5 cases.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical effects of ceftizoxime suppositories in pediatric infections

A clinical trial of ceftizoxime suppositories (CZX-S) was conducted in children whose chemotherapy was considered to be best performed in this dosage form at the physician's discretion. The subjects were 5 children with infection, consisting of 2 with pneumonia, 1 with tonsillitis, and 2 with UTI. The results were as follows. The clinical response to CZX-S was "markedly effective" in 3 and "effective" in 2, with the 100% effectiveness rate. Neither adverse drug reactions nor abnormal laboratory tests were detected. No unwanted expulsion of the suppository occurred. The serum concentration of CZX 30 minutes after the first insertion ranged from 8.38 to 11.4 micrograms/ml, and the urinary concentration of CZX in the 6-hour urine collections, from 23.6 to 290 micrograms/ml.     

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.     

Basic and clinical studies of ceftizoxime suppositories in the pediatric field

A bacteriological and clinical study of ceftizoxime suppositories (CZX-S) let to the following results. The CZX serum concentration 10 minutes after insertion of one 250 mg suppository (i.e. 5.7-15.2 mg CZX per kg body weight) ranged from 1.64 to 6.53 micrograms/ml (average: 4.41 micrograms/ml). In one child the concentration 7 minutes after insertion was 4.13 micrograms/ml. Therapeutic responsiveness was recorded as "effective" in 8 (88.9%) of the 9 children who were broken down into 6 with tonsillitis, 1 with pharyngitis, and 2 with UTI. Bacteriological studies conducted in 5 children have confirmed eradication in 4 children, one of whom showing appearance of another strain. The rate of discharge of the suppository within 10 minutes after insertion was 20.4%. Reddening and erosion of the anus were observed in 1 child.     

Experimental and clinical studies on ceftizoxime in the field of oral surgery (author's transl)

Experimental and clinical studies on ceftizoxime (CZX), a new cephalosporin derivative, were carried out and the following results were obtained. 1. The minimal inhibitory concentrations of CZX, cefazolin (CEZ), cephalothin (CET), cefotiam (CTM) and cefmetazole (CMZ) against Gram-positive cocci (31 strains) and Gram-negative rods (169 strains) isolated from the patients with oral infections were determined. CZX, though somewhat less active against Gram-positive cocci than the other cephalosporins, was the most active of the antibiotics tested against Gram-negative rods. 2. The mean serum levels in 19 patients who received 1 g of CZX by intravenous drip infusion for 1 hour were as follows. 19.6 micrograms/ml 30 minutes after the start of intravenous drip infusion, 52.2 micrograms/ml after 1 hour, 25.0 micrograms/ml after 1.5 hours, 20.3 micrograms/ml after 2 hours, 7.9 micrograms/ml after 4 hours, 3.5 micrograms/ml after 6 hours. The mean peak tissue levels of CZX after 1 g dose by intravenous drip infusion for 1 hour were 14.3 micrograms/g (n = 5) in gingiva and 8.5 micrograms/g (n = 2) in bone marrow at the end of intravenous drip infusion. 3. CZX was administered to 17 patients with various infections in the oral surgical field at daily dose of 1 approximately 2 g for 3 approximately 6 days. The therapeutic effect was as follows: 'excellent' in 6 cases, 'good' in 9, 'fair' in 1 and 'poor' in 1. The final rate of effectiveness was 88.2%. No adverse reaction was observed except for 2 cases of slight elevation of S-GPT.     

Clinical investigation of ceftizoxime sodium suppositories in pediatric infections

Ceftizoxime suppository (CZX-S) was given to 6 patients, with the following results. The peak serum concentration of CZX was 1.8-7.5 micrograms/ml at 30 minutes after dosing of CZX-S with 9.6-16.7 mg/kg. The antibacterial activity of CZX revealed that the drug can be expected to be effective sufficiently. The overall effect of CZX-S was "markedly improved" in 1 and "moderately improved" in 3 of the 4 patients with pneumonia and "markedly improved" in 1 and "slightly improved" in 1 of the 2 with UTI. CZX-S caused a slight increase in frequency of defecation in 2 of the 6 patients. There were no abnormal findings of symptoms or laboratory test values which were ascribable to side effects.     

Pharmacokinetic and clinical studies of ceftizoxime in obstetrical and gynecological field (2)

Pharmacokinetic and clinical evaluations of ceftizoxime (CZX) in 3 obstetrical and gynecological clinics have substantiated the therapeutic usefulness of this drug in the relevant specialty. The results are summarized below. 1. The peak serum CZX concentration after drip infusion of 2 g given over 60 minutes was 115.3 micrograms/ml. The peak CZX concentration in the pelvic dead space exudate was 34.10 micrograms/ml which was attained 2.02 hours after beginning infusion. Half-lives of CZX in the serum and in the pelvic dead space exudate were 1.64 hours and 3.65 hours, respectively. 2. The passage of infused CZX to the umbilical cord serum was satisfactorily rapid, as evidenced by figures reaching 10 micrograms/ml or higher at 1 hour and 15 minutes and still as high as 3 micrograms/ml or higher at 6 hours after administration. 3. The passage of CZX to the milk of mothers receiving this drug was low, and no untoward effect on the infant was likely. 4. CZX would effectively prevent infections due to premature ruptures of membrane.     

Laboratory and clinical studies on ceftazidime in the field of pediatrics

Laboratory and clinical studies on ceftazidime ( CAZ ), a new cephem antibiotic, were carried out in the field of pediatrics. The results were as follows: Antibacterial activities of CAZ against clinically isolated strains of S. pneumoniae, H. influenzae, E. coli and P. aeruginosa were compared with those of cefotaxime (CTX), ceftizoxime (CZX), latamoxef ( LMOX ), cefoperazone (CPZ) and cefmetazole (CMZ), and also with cefsulodin (CFS) and gentamicin (GM) against P. aeruginosa. Against S. pneumoniae and H. influenzae, CAZ was almost as active as CTX, CZX and CPZ. Against E. coli, it was almost as active as CTX, CZX and LMOX . Against P. aeruginosa, it was almost as active as CFS and GM. Serum concentrations and urinary excretion rates after intravenous bolus injection of CAZ at doses of 20 mg/kg and 10 mg/kg for 5 minutes in each 2 cases (4 cases in total) were determined. The mean serum concentrations of CAZ were 78.9 and 52.0 micrograms/ml at 15 minutes, 38.5 and 27.4 micrograms/ml at 1 hour, and 6.5 and 4.8 micrograms/ml at 4 hours, with serum half-lives (T 1/2) of 1.39 and 1.80 hours respectively. Mean cumulative urinary excretion rate within 6 hours after administration was 84.6%. In a patient with chronic renal failure, serum half-life was 3.22 hours and urinary excretion rate within 6 hours was 22.8% (after intravenous bolus injection of CAZ at a dose of 10 mg/kg). CAZ was administered at a dose of 55.5 mg/kg by intravenous bolus injection to a child with purulent meningitis. The levels of CAZ in the cerebrospinal fluid (CSF) at 1 hour after administration were 2.7-38.9 micrograms/ml with CSF/Serum ratios of 3.2-28.8%. Forty-two pediatric patients with various bacterial infections (pyelonephritis 14, tonsillitis 1, bronchopneumonia 3, pneumonia 17, purulent meningitis 1, bacteremia 2, SSSS 1, enterocolitis 3) were treated with CAZ at a daily dose of 49-222 mg/kg t.i.d. or q.i.d. (as a rule 60 mg/kg t.i.d.). The efficacy rate was 97.6% clinically and 97.8% bacteriologically. No adverse reactions were observed except 1 case with mild diarrhea. Abnormal laboratory findings were also only mild; eosinophilia in 1, slight elevation of GOT in 5 and that of GOT & GPT in 3 cases. These results indicate the usefulness of CAZ in the treatment of bacterial infections in children.