The Basic and Clinical Studies on Cefotetan in Pediatric Field

Satoshi Iwata, Yukio Iwasaki, Takefumi Kanemitsu, Masahiro Tojo, Keiji Jozaki, Hironobu Akita, Yoshifumi Kojima, Ryo Wakabayashi, Keisuke Sunakawa, Mitsuru Osano, Hirotaka Takahashi, Yasuo Tachibana, Jun Ishihara, Takeo Kori

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Abstract

Preclinical studies were carried out on cefotetan (CTT), together with clinical studies in the field of pediatrics. The following results were obtained. 1. A total of 114 clinical isolates that have been stored in the authors’ department was employed to determine the minimum inhibitory concentrations (MICs) of CTT against various bacterial species. Against E. coli, Salmonella, K. pneumoniae and P. mirabilis, the MICs of CTT showed a peak at 0.78;μ/ml, and most of the strains were inhibited by a CTT concentration of 6.25 µg/ml or less. The MICs for S. marcescens strains showed a peak at 25 µg/ml, with 25% of the strains having MICs of 3.13 µ/ml or less, and 67% having MICs of 25 µg/ml or more. All of the P. aeruginosa strains had MICs of over 100 µg/ml. Against all of the tested strains of S. aureus, a Gram-positive bacterium, CTT showed MICs of 12.5 µg/ml or more, while all of the strains of S. faecalis were found to have MICs of over 100 µg/ml. 2. CTT was administered intravenously to pediatric patients as a bolus injection, and then the concentration of the antibiotic in the serum was determined as a function of time. When the dosage rate was 10 mg/kg, the mean serum levels were as follows; 58.2µg/ml at 30 minutes, 45.5 µg/ml at 1 hour, 33.6;Kg/ml at 2 hours, IS.OjKg/ml at 4 hours and 11.7µg/ml at 6 hours after the injection. The half-life of CTT in the serum at this dosage was thus 2.40 hours. Similarly, at a dosage rate of 20 mg/kg, the mean values at the various times were; 98.6;Mg/ml at 30 minutes, 75.6µg/ml at 1 hour, 57.8 µg/ml at 2 hours, 35.5 µg/ml at 4 hours and 23.2 µg/ml at 6 hours subsequent to the injection. The half-life of CTT in the serum in these cases was 2.73 hours. 3. CTT was drip-infused intravenously over a period of 1 hour, and then the serum concentration of the drug was monitored with the passage of time. Subsequent to the administration of 10 mg/kg, the mean serum concentrations were as follows; 48.8 µg/ml at 30 minutes, 81.5 µg/ml at 1 hour, 42.2 µg/ml at 2 hours, 23.6 µg/mi at 4 hours and 14.8 µg/ml at 6 hours subsequent to the injection. The half-life of CTT in the serum after this intravenous drip infusion was thus 2.13 hours. Similarly, when the dosage rate was 20 mg/kg, the mean values at the measurement times were 78.8 µg/ml at 30 minutes, 138.2 µ/ml at 1 hour, 7L1/ig/ml at 2 hours, 41.8 µg/ml at 4 hours and 31.7 µg/ml at 6 hours subsequent to the injection. The half-life of CTT in the serum at this dosage rate was 2.48 hours. 4. CTT was administered to 3 meningitis patients, and then the concentration of the antibiotic in the cerebrospinal fluid was measured with the course of time. A single dose of CTT, ranging from 54 to 83 mg/kg, was administered, and the CSF concentration ranged from 1.1 to 4.8µg/ml. The ratio of the concentration in the CSF to the serum concentration ranged from 0.8 to 3.6%. 5. No cumulative effect of CTT was seen. 6. CTT was administered intravenously to 16 cases of bacterial infection. A good clinical effect was seen in 14 of these cases (88%). 7. The bacteriological effect of CTT was investigated in 9 patients. In all cases, the causative bacteria were eliminated, for a 100% bacteriological efficacy rate. The bacterial isolates consisted of 5 strains of E. coli, 2 strains of 5. pneumoniae, 1 strain of H. influenzae, and 1 strain of H. parainfluenzae. 8. The following side effects to the CTT therapy were recorded; 4 cases of diarrhea, and elevated values of GOT and GPT in 1 patient. All of these side effect symptoms disappeared rapidly after the drug administration was stopped.

Original languageEnglish
Pages (from-to)1204-1218
Number of pages15
Journalthe japanese journal of antibiotics
Volume36
Issue number6
DOIs
Publication statusPublished - 1983

ASJC Scopus subject areas

  • Microbiology (medical)
  • Pharmacology (medical)
  • Infectious Diseases

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    Iwata, S., Iwasaki, Y., Kanemitsu, T., Tojo, M., Jozaki, K., Akita, H., Kojima, Y., Wakabayashi, R., Sunakawa, K., Osano, M., Takahashi, H., Tachibana, Y., Ishihara, J., & Kori, T. (1983). The Basic and Clinical Studies on Cefotetan in Pediatric Field. the japanese journal of antibiotics, 36(6), 1204-1218. https://doi.org/10.11553/antibiotics1968b.36.1204