[A clinical study on cefteram pivoxil in pediatrics].

Clinical evaluations of cefteram pivoxil (CFTM-PI, T-2588) were carried out. The obtained results are summarized as follows. 1. Clinical responses to CFTM-PI of 39 patients with pediatric infections were excellent in 16, good in 21, fair in 1 and poor in 1. The overall efficacy rate was 94.9%. 2. Bacteriologically, eradication rates for 39 isolates presumed to be pathogens were evaluated. The eradication rates obtained were 94.1% in 17 strains of Gram-positive cocci, 90.9% in 22 strains of Gram-negative rods. 3. Side effects observed were diarrhea in 2 patients, diarrhea and abdominal pain in 1, erythema and edema in 1. The incidence was 8.7%. An abnormal value found in clinical laboratory tests was eosinophilia in 1 patient. The results suggested that CFTM-PI might be a very useful and safe drug for the treatment of pediatric infections.

[Clinical studies on cefteram pivoxil granules in pediatrics].

A newly developed cephalosporin, cefteram pivoxil (CFTM-PI, T-2588), was evaluated clinically in 40 patients. A pharmacokinetic study was also performed with 8 patients. CFTM-PI was administered as granules. One patient was given CFTM-PI at a dose of 1.5 mg/kg, each of 3 patients was given the drug at a dose of 3 mg/kg and each of 4 patients at a dose of 6 mg/kg. In most cases, serum concentrations of CFTM were determined at 2, 3, 4, and 6 hours after dosing. Urinary concentrations of CFTM were measured for urinary samples collected during periods of 0-2, 2-4, 4-6 and 6-8 hours after dosing. CFTM was assayed using the disk or the cup method using Klebsiella pneumoniae ATCC 10031 as the test organism. The clinical evaluation was conducted in 40 children including 13 patients of acute tonsillitis, 10 of acute lacunar tonsillitis, 10 of scarlet fever, 2 of acute bronchitis, 2 of pneumonia, and 1 each of pneumonia with enteritis, phlegmon and urinary tract infection. The patients were from 4 months to 13 years old. Daily doses were from 8.7 to 12 mg/kg. After CFTM-PI administration in doses 1.5 mg/kg, 3 mg/kg and 6 mg/kg, peak serum concentrations of CFTM were 0.38 microgram/ml, 0.73-2.25 micrograms/ml and 1.2-2.9 micrograms/ml, respectively, and half-lives were 1.55, 0.95-2.30 and 0.80-2.72 hours, respectively. Urinary excretion rates up to 6 or 8 hours after dosing were 10.8-24.7%. Clinical efficacies of CFTM-PI in 40 patients were "excellent" in 27 children, "good" in 12 children and "fair" in 1 with an efficacy rate of 97.5%. Twenty seven strains of causative organisms, including 15 strains of Streptococcus pyogenes, 1 of Escherichia coli, 1 of Salmonella 04, 6 of Haemophilus influenzae, 1 of Haemophilus parainfluenzae and 3 of Branhamella catarrhalis, were isolated. After treatment all strains except 1 strain of B. catarrhalis (unchanged), Salmonella 04 (unknown) and 1 strain of H. parainfluenzae (unknown) were eradicated. Side effects observed clinically were only 1 case of diarrhea. Eosinophilia was observed in 1 case.

[A clinical study on cefteram pivoxil granule in the field of pediatrics].

The clinical effectiveness of cefteram pivoxil (CFTM-PI) granule, a new oral cephalosporin, was studied in pediatric patients. The results are summarized as follows. 1. CFTM-PI was given orally to 17 children in daily doses of 9.5 to 31.8 mg/kg in 3 to 4 divided portions for 2 to 10 days. Clinical evaluations were made on 14 patients. Clinical effects of CFTM-PI were excellent in 4, good in 5 of 9 patients with tonsillitis or pharyngitis, excellent in all cases of 2 patients with pneumonia, 1 patient with scarlet fever and 1 patient with pyelonephritis, and fair in 1 patient with purulent cervical lymphadenitis. Overall clinical effects were excellent in 8, good in 5, and fair in 1 with an efficacy rate of 92.9%. 2. No side effects were observed in any of the 17 patients. Hematological tests showed a slight elevation of blood platelet counts in 1 patient. 3. The taste and odor of CFTM-PI granule were well accepted by the children. 4. CFTM-PI is a useful oral antibiotic for the treatment of bacterial infections in pediatrics.

[Study on the effectiveness and safety of cefmenoxime in the treatment of respiratory tract infections. Tendency toward clinical hemorrhage related to the treatment].

The effectiveness and safety of cefmenoxime (CMX) in the treatment of respiratory tract infections were evaluated, mainly in relation to the appearance of hemorrhagic tendency. Out of 80 patients treated in this study, 57 were treated with CMX alone, and an effective rate was determined to be 75.4%. As for a tendency toward hemorrhage, none of the patients clinically exhibited a hemorrhagic tendency, while the prolongation of prothrombin time (PT) and/or activated partial thromboplastin time (APTT) was seen in 3 patients (3.8%), who were all at ages over 63. The prolongation of APTT was clearly related to CMX in 1 patient. Although the causal relation between CMX and the prolongation of PT or APTT was unclear in the remaining 2 patients because they had severe primary diseases (lung cancer and respiratory failure due to chronic obstructive lung disease in addition to severe hepatic disorder and received combination treatment with anticancer agents or other antibiotics), CMX might have a role in causing these phenomena. Even though none of the patients showed a hemorrhagic tendency clinically arousing problems, we should be careful in using CMX in the treatment of the aged and patients in poor general conditions because PT and/or APTT was observed to prolong with the use of CMX in some patients.

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

Pharmacokinetic and clinical studies on cefmenoxime (CMX) in neonates and premature infants were conducted. The results are summarized as follows. 1. Intravenous administration of CMX at 20 mg/kg, via bolus injection or 1-hour drip infusion, produced at sufficiently high blood concentration. As it is the case with other cephem antibiotics, the half-life varied with age and tended to become shorter with aging. 2. There were intergroup differences in urinary recovery of the drug, but urinary concentrations were generally high. 3. In the clinical evaluation, 12 out of 15 cases which were evaluable for efficacy were rated "excellent" or "good". 4. Side effects were evaluated in 27 cases. A bleeding tendency was found in 1 case, eosinophilia in 1 case, elevated GOT in 1 case, and positive PIVKA II in 4 cases. It is, therefore, concluded that CMX is a highly useful drug for the treatment of bacterial infections in neonates and premature infants.

[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)

[Laboratory and clinical studies on cefteram pivoxil in pediatric field].

Pharmacokinetic and clinical studies of cefteram pivoxil (CFTM-PI, T-2588) fine granules in children were performed and the following results were obtained. 1. Peak serum concentrations in 4 children given orally a dose of 3 mg/kg and 2 children given orally a dose of 6 mg/kg after meal were reached in 3 to 4 hours and the concentration curves were dependent on dosage levels. The urinary recovery rates up to 8 hours were 29.7% in children given a dose of 3 mg/kg and 29.7% in children given a dose of 6 mg/kg. 2. Clinical efficacies were evaluated in 38 patients with bacterial infections. Twenty seven patients were given each doses of 3 mg/kg in 3 times a day and other 11 patients each doses of 6 mg/kg in 3 times. Clinical effects of CFTM-PI were excellent in 18, good in 19, fair in 1 case, hence the overall clinical efficacy rate was 97.4%. 3. Bacteriologically, 24 strains of causative organisms were isolated. The overall bacteriological eradication rate was 81.8%. Antimicrobial activities were excellent especially against Streptococcus pyogenes, Streptococcus pneumoniae, and Haemophilus influenzae. 4. As for the side effects, slight loose stools were observed in 2 cases, and in laboratory tests, elevations of GOT and GPT were observed in 1 case and an elevation of eosinophil was observed in 1 case. But no one needed any treatment. 5. CFTM-PI is a useful and safe oral antibiotic for the treatment of bacterial infections in pediatrics.

[Clinical observations with cefteram pivoxil granules in field of pediatrics].

A new oral cephem antibiotic, cefteram pivoxil (CFTM-PI, T-2588), was studied for clinical efficacy in the field of pediatrics. CFTM-PI was given orally to 23 patients with the following acute bacterial infections: 6 cases of acute tonsillitis, 8 of acute bronchitis, 2 of scarlet fever, 4 of bronchopneumonia, 1 of acute otitis media with sinusitis and 2 of urinary tract infections. Clinical results were "excellent" in 8, "good" in 14, "poor" in 1: the efficacy rate was 95.7%. As an adverse reaction, diarrhea was observed in 1 patient. From the above clinical results, it appears that CFTM-PI is a useful antibiotic for the treatment of pediatric patients with various bacterial infections.

[Clinical evaluation of cefteram pivoxil in the pediatric field].

Cefteram pivoxil (CFTM-PI, T-2588), a new oral cephalosporin antibiotic, was evaluated for its safety and efficacy in children. Fifty-three patients with bacterial infections were treated with 8.3 to 21.8 mg/kg/day of CFTM-PI. The drug was very effective (efficacy rate 98.1%) in pharyngitis, otitis media, tracheobronchitis, pneumonia and skin infections. The antibacterial potency was very good against Haemophilus influenzae, Streptococcus pyogenes and Streptococcus pneumoniae, and was comparable with cephalexin against Staphylococcus aureus. No severe adverse reaction was encountered with the CFTM-PI therapy. The data suggest that CFTM-PI is a safe and effective antibiotic when used in children with susceptible bacterial infections.

[Clinical studies on cefteram pivoxil in the field of pediatrics].

Cefteram pivoxil (CFTM-PI) was administered to 37 patients with acute febrile upper or lower respiratory infections and 3 patients with urinary tract infections at 10 mg/kg/day divided into 3 portions. Good clinical effects were observed in all the cases. As for the bacteriological effect, the evaluable 24 strains (60.0%) were eradicated among 43 strains identified in 37 cases with the treatment with CFTM-PI. Only 2 strains were eradicated among 9 strains of Staphylococcus aureus. Among 3 patients with urinary tract infections with Escherichia coli, 2 strains were eradicated from urine after the administration of CFTM-PI. Four cases showed mild diarrhea among 40 cases. It was not clear whether the diarrhea was due to the administration of CFTM-PI.

[Clinical study on cefteram pivoxil in pediatric field].

Cefteram pivoxil (CFTM-PI, T-2588) was administered to pediatric patients with acute infectious diseases, and a summary of the results obtained are as follows. 1. Pharmacokinetic parameters determined in 1 patient appears to be comparable to those of adults. 2. Clinical efficacy was studied on 16 children with acute urinary tract infections, acute upper respiratory infections, acute sinusitis, acute otitis media and acute cervical lymphadenitis. Responses to the treatment were excellent in 7 (43.8%) and good in 9 (56.3%). 3. No adverse reactions were noted in this study.

[A clinical study on cefteram pivoxil in the field of pediatrics].

Cefteram pivoxil (CFTM-PI, T-2588), a new oral cephem antibiotic of ester type, was evaluated for its safety, efficacy and pharmacokinetics. 1. One child, 4 years of age (18 kg body weight), was administered orally 3 mg/kg after meal. The peak serum level of CFTM was 0.78 microgram/ml after 2 hours, and cumulative urinary excretion rate during the first 6 hours was 15.0%. 2. Clinical studies on CFTM-PI were carried out in 17 pediatric patients; 1 with acute pharyngitis, 2 with acute tonsillitis, 1 each with pertussis, acute bronchitis, 2 with broncho-pneumonia, 4 with scarlatina, 3 with acute otitis media, and 1 each with lymphadenitis, acrobystitis and urinary tract infection. Clinical responses were excellent in 9, good in 6, fair in 1, poor in 1, and the overall clinical efficacy rate was 88.2%. 3. Bacteriological efficacy was investigated with 10 strains of 5 species (Streptococcus pyogenes 4, Streptococcus pneumoniae 2, Haemophilus influenzae 2, Enterococcus and Bacteroides 1) isolated from 9 patients. All strains were eradicated. 4. As to adverse reactions, mild diarrhea was observed in 1 patient. But therapy had to be continued without procedure and the diarrhea disappeared after 6 days. No adverse hematological, renal or hepatic effects were noted.

[Clinical studies of cefteram pivoxil in pediatrics].

The clinical efficacy and the safety of cefteram pivoxil granule (CFTM-PI, T-2588), a newly prepared drug for pediatric use, were performed. A total of 60 patients with ages between 6 months and 14 years 3 months with pediatric infections were medicated with CFTM-PI at dose levels of 3.2-9.9 mg/kg 3 times daily for 3-11 days. Clinical responses to the drug were excellent in 3 of 3 patients with acute pharyngitis, excellent in 14, good in 5 and poor in 2 of 21 patients with acute purulent tonsillitis, excellent in 1 and good in 2 of 3 patients with acute bronchitis, excellent in 16 and good in 8 of 24 patients with acute pneumonia, excellent in 3 and good in 1 of 4 patients with acute urinary tract infection and excellent in 2 of 2 patients with acute purulent lymphadenitis, hence the overall clinical efficacy rate was 96.5% in a total of 57 patients. Bacteriological responses to the drug were as follows: Eradicated, 8 strains of Streptococcus pyogenes, 3 strains of Streptococcus pneumoniae, 19 strains of Haemophilus influenzae (beta-lactamase positive; 7, beta-lactamase negative; 12), 1 strain of Haemophilus parainfluenzae (beta-lactamase positive) and 4 strains of Escherichia coli (beta-lactamase positive; 1, beta-lactamase negative; 3), decreased, 1 strain of S. pyogenes, hence the eradication rate was 97.2%. No side effects were encountered in any of the patients but for 3 who had diarrhoea and 1 who had loose stool, though these changes were slight. As abnormal laboratory test data, elevation of GOT was noted in 1 case, thrombocytosis and elevation of GPT in another. Also, none of the patients refused or complained of difficulty in intaking of the drug via oral route. In conclusion, CFTM-PI appeared to be a safe and highly effective antibiotic against pediatric infections.

[Laboratory and clinical studies of cefteram pivoxil in pediatric field].

We have carried out laboratory and clinical studies on cefteram pivoxil (CFTM-PI, T-2588). The results are summarized as follows. CFTM-PI was given through oral administration to 2 children each at dose levels of 1.5 mg/kg, 3 mg/kg and 6 mg/kg. After administration, mean peak serum levels of CFTM obtained for the 3 dose levels were 0.66 +/- 0.01 microgram/ml, 1.26 +/- 1.05 micrograms/ml and 2.28 +/- 0.95 micrograms/ml at 2 hours, respectively, and mean half-lives were 1.07 +/- 0.52 hours, 1.32 +/- 0.76 hours and 2.53 +/- 1.70 hours, respectively. Mean urinary excretion rates of CFTM were 19.0 +/- 4.0%, 9.4 +/- 1.5% and 19.9 +/- 4.0% in the first 8 hours after administration of 1.5 mg/kg, 3 mg/kg, 6 mg/kg, respectively. Treatment with CFTM-PI was made in 36 cases of pediatric bacterial infections including 20 cases of tonsillitis, 3 cases of bronchitis, 6 cases of scarlet fever, 3 cases of UTI and 1 case each of bronchopneumonia, abscess, staphylococcal scalded skin syndrome and vaginitis. Results obtained were excellent in 22 cases, good in 14 cases. No significant side effect due to the drug was observed in any cases.

[Clinical evaluation of cefteram pivoxil in respiratory tract infections].

The usefulness of cefteram pivoxil (CFTM-PI) was evaluated in 99 cases with respiratory tract infections: 32 cases with acute bronchitis, 51 cases with infectious exacerbations of chronic respiratory diseases and 16 cases with pneumonia. 1. The clinical efficacies included marked improvement in 27 cases, improvement in 51 cases, moderate improvement in 9 cases, no change in 10 cases and deterioration in 2 cases. The improvement rate was 78.8%. 2. Overall effects were excellent in 12 cases, good in 9 cases and fair in 5 cases. There was no case in which efficacy was not observed and the efficacy rate was 80.8%. 3. Bacteriological effects were classified according to the causative organisms. Eradication rate was 80.8% (21 of 26 strains), indicating an excellent antibacterial action of CFTM-PI. In particular, MICs of cefteram were below 0.05 microgram/ml against all 10 strains of Haemophilus influenzae regardless of beta-lactamase production even with an inoculum of 10(8) or 10(6) cells/ml. 4. Side effects rarely occurred and included a slight gastrointestinal irritation in 4 of 99 cases (4%). Two cases which had abnormal elevations of GOT and GPT had abnormal values prior to administration of CFTM-PI. The elevations were slight and it was possible to continue administration. The GOT and GPT values were improved after the end of administration. The above results indicate the usefulness of CFTM-PI in acute respiratory infections and infectious exacerbation of chronic respiratory diseases.

[A preclinical and clinical study of cefmenoxime in newborns].

1. Cefmenoxime (CMX) was administered with a dosage regimen of 20-25 mg/kg, 2-3 times daily (40-75 mg/kg/day) by intravenous drip over 30 minutes to 9 neonates with bacterial infections including purulent meningitis and septicemia. Clinical responses to the treatment were excellent in 7 and poor in 2. Bacteriological responses were "eradication of pathogens" from 8 of them except another patient with an infection due to Staphylococcus aureus. 2. Adverse reactions to CMX were observed in 6 of 18 neonates treated with the drug: diarrhea, oral thrush, and the elevation of S-GOT, S-GPT, LDH and alkaline phosphatase. None of the reactions, however, necessitated the discontinuation of the treatment. 3. Changes in blood concentrations of CMX in neonates with ages between 0 and 30 days were followed. These subjects included 16 mature neonates and 10 neonates with low birth weights. Intravenous drip infusion of 20 mg/kg of CMX over 30 minutes was immediately followed by peak blood CMX concentrations of 34.6-72.7 mcg/ml (mean +/- S.D.: 50.4 +/- 11.3 mcg/ml) in the mature neonates, and 22.3-78.2 mcg/ml (55.5 +/- 16.5 mcg/ml) in the neonates with low birth weight. Blood half-lives of the drug in the mature neonates were in the range from 1.7 to 20.7 hours (5.9 +/- 6.6 hours) in subjects with ages of 0-3 days, and 1.1-3.5 hours (2.0 +/- 0.8 hours) in subjects of 4-25 days. In neonates with low birth weight, they were 3.4-10.2 hours (7.2 +/- 2.7 hours) in subjects of 0-2 days, and 1.4-5.5 hours (3.0 +/- 1.5 hours) in subjects of 4-30 days. In other words, the blood half-lives of the drug tended to be longer in younger subjects. 4. Concentration of CMX in cerebrospinal fluid (CSF) were determined in a patient in acute stage with purulent meningitis caused by Mycoplasma hominis. Intravenous drip infusion of 80 mg/kg of CMX over 30 minutes was followed by CSF concentrations of 7.7-15.5 mcg/ml. 5. MICs of CMX for clinical isolates were determined. The drug was proved to have excellent antibacterial activities against Escherichia coli (3 strains) and group B hemolytic streptococci (2 strains) and these MICs were comparable to those of cefotaxime. The MIC of CMX for S. aureus (1 strain) was high at 25 mcg/ml with an inoculum size of 10(8) CFU/ml. This MIC value of CMX was higher than that of cefmetazole.