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.     

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.     

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 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 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.     

Clinical experience with ceftizoxime suppositories in bacterial infections in children

A clinical trial of ceftizoxime suppositories (CZX-S) was performed to evaluate the therapeutic effectiveness in children with bacterial infection. The subjects were 10 children comprising 4 with pneumonia, 3 with lacunar tonsillitis, 2 with pharyngitis, and 1 with UTI. They were given 1 suppository containing either 125 mg or 250 mg of CZX 2 to 4 times a day. The daily per kg body weight dose ranged from 17.1 to 60.0 mg. The result was "markedly effective" in 3, "effective" in 6, and "failure" was recorded in 1. Bacteriologically, successful eradication of causative organisms was confirmed in all the 4 children who underwent the test. No clinical side effects were observed. The only laboratory test abnormality recorded in a single patient was eosinophilia, which was not definitely ascribable to CZX-S. In conclusion, CZX-S have proved to be a clinically safe and effective antibiotic preparation in infantile infection, even in children whose treatment with conventional antibiotics is associated with difficulties.     

Clinical effect of ceftizoxime suppositories

The therapeutic effect of ceftizoxime suppositories (CZX-S) was studied in 8 physically handicapped patients, comprising 6 with pharyngitis, 1 with pneumonia, and 1 with urinary tract infection. The clinical effect was "excellent" in 7 and "good" in 1. Neither adverse reactions nor abnormal laboratory test findings attributable to CZX-S were detected. CZX-S proved to be useful in physically handicapped children, especially in those not suited to treatment with oral or intravenous preparations.     

Clinical experience with ceftizoxime suppositories in pediatrics

Ceftizoxime suppositories (CZX-S), containing 250 mg or 125 mg of CZX, were given to 6 children, 4 with acute bronchopneumonia and 2 with acute pharyngobronchitis, who were not suited to treatment with injectable or oral form of the drug. The clinical response was "good" in all the children and the causative organisms were eradicated in 2 children (H. influenzae or S. aureus). Adverse reactions consisted of 1 case each of diarrhea and transiently increased GPT. In conclusion, CZX-S proved to be highly effective in the treatment of bacterial infections in children.     

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.     

Clinical use of ceftizoxime suppositories in pediatric infection

Ceftizoxime suppositories (CZX-S) were given to 5 children comprising 3 with acute bronchitis, 1 with acute bronchitis complicated by enteritis, and 1 with acute urinary tract infection, in doses of 12.5 12.5-17.4 mg/kg with 1 suppository containing 125 mg or 250 mg (potency) given 3 times a day. The clinical response was "markedly effective" in 2 and "effective" in 3. Microbiologically CZX-S caused a eradication of 1 strain each of S. aureus and E. coli and caused a decrease of organisms in 1 strain of S. aureus. There were no adverse reactions or abnormal laboratory test findings attributable to CZX-S. In conclusion, CZX-S proved to be a clinically useful antibiotic preparation for the treatment of infection in children not suited to treatment with oral or intravenous preparations.     

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 the pediatric field

Ceftizoxime suppository (CZX-S) was given to 19 children with infections, including upper and lower respiratory tract infections, urinary tract infections and otitis media at dose level of 18-83 mg/kg/day divided into 2-3 times. Clinical response was excellent in 12 patients, good in 6 patients and poor in 1 patient. Bacteriological response was eradicated in 11 strains, decreased in 3 strains and unchanged in 4 strains. No severe side effects were observed with this drug. These results obtained suggest that CZX-S should be a useful antibiotic in treatment of infections in pediatric field.     

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.     

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.     

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.     

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.     

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

Ceftizoxime was tried in children with various infections and the following results were obtained. 1) Serum levels and urinary recovery of ceftizoxime were studied in 6 patients aged from 6 to 10 years. After intravenous bolus injection of 20 mg/kg, the mean serum concentrations were 113.9 micrograms/ml, 47.6 micrograms/ml, 31.8 micrograms/ml, 18.5 micrograms/ml, 6.3 micrograms/ml and 2.1 micrograms/ml at 5 minutes, 30 minutes, 1 hour, 2 hours, 4 hours and 6 hours, respectively. The average urinary recovery rates of ceftizoxime were 55.1%, 90.9% and 98.3% at 2 hours, 4 hours and 6 hours after the administration, respectively. 2) The therapeutic efficacy was excellent in 11, good in 9 and poor in 2 patients, the efficacy rate being 91%. 3) As for the side effects, elevation of S-GOT and S-GPT, and drug fever were observed in 1 case, but disappeared soon after discontinuation of the therapy.     

Fundamental and clinical studies of ceftizoxime in obstetrical and gynecological field

This paper, is concerned with fundamental and clinical studies of ceftizoxime, a newly developed cephalosporin derivative, in the field of obstetrics and gynecology. 1. Concentrations of ceftizoxime after administration 1 g of ceftizoxime by 1 hour drip infusion were determined in genital organs in 17 patients and the exudate of pelvic dead space in 6 patients. Simulated maximal concentrations with the ratios to the simulated peak serum levels were as follows: 27.9 micrograms/g for fundal myometrium with the ratio of 48%, 36.0 micrograms/g for portio vaginalis with 62%, 17.1 micrograms/g for ovary with 29%, 15.0 micrograms/g for oviduct with 26% and 16.2 micrograms/ml for the exudate of pelvic dead space with 30%. 2. Minimal inhibitory concentrations of ceftizoxime were determined against clinically isolated organisms from female genital infectious diseases. Ceftizoxime was found to have a potent in vitro activity against Gram negative bacilli; for example, 0.1 microgram/mg or low against E. coli and K. pneumoniae. Against P. aeruginosa, P. cepacia and b. fragilis, ceftizoxime had an activity which expected to be effective in the clinical use. 3. We gave ceftizoxime to 6 patients comprising 4 patients with puerperal fever, 1 with septic abortion and 1 with tubo-ovarian abscess in daily doses of 2 to 3 g by b.i.d or t.i.d intravenous drip infusion for 4--12 days. The results of the treatment were 'excellent' in 3 patients, 'good' in 2, and 'unevaluatable' in 1. 4. Adverse reactions occurred in 2 patients who showed eruption during the medication with ceftizoxime. These patients had allergic histories due to penicillin derivatives. From the above results it is concluded that ceftizoxime is a useful drug for infections in obstetrical and gynecological field.     

Fundamental and clinical studies in pediatric field on ceftizoxime (author's transl)

Fundamental and clinical studies in the pediatric field on ceftizoxime were carried out, and the following results were obtained. 1. In 4 children age from 3 years to 5 years, the serum concentrations and urinary excretion of ceftizoxime in a dose of 20 mg/kg by intravenous drip infusion over 60 minutes were measured. The peak serum levels were 22.0--84.0 microgram/ml (mean 45.0 microgram/ml) at the end of infusion. The mean serum levels after the end of infusion were 16.9 microgram/ml at 30 minutes, 12.1 microgram/ml at 1 hour, 6.2 microgram/ml at 2 hours, 1.6 microgram/ml at 4 hours and 0.6 microgram/ml at 6 hours, with mean serum half-life (T 1/2) of 1.03 hours, mean urinary recovery rate was 64.9% up to 6 hours. 2. Concentrations of the drug in the cerebrospinal fluid in 1 patient with purulent meningitis at 30 minutes after an intravenous drip infusion of about 33.3 mg/kg were 0.2 to 1.5 microgram/ml, which were 8 to 60 times higher than the MICs of the causative organisms. 3. Ceftizoxime was administered to 38 children with pneumonia, bronchitis, Salmonella enteritis, purulent meningitis, etc. in the daily dose of 44--200 mg/kg for 3--19 days. Clinical response was excellent in 24, good in 12, poor in 1 and unknown in 1. The drug was proved to be very effective in 1 case of purulent meningitis due to H. influenzae. As for side effect, eruption was observed in only 1 case.