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  • Title: [Laboratory and clinical studies on ceftizoxime in the field of pediatrics (author's transl)].
    Author: Toyonaga Y, Kurosu Y, Sugita M, Kawamura G, Okuyama M, Yoshino N, Hori M, Takahashi T.
    Journal: Jpn J Antibiot; 1982 Jan; 35(1):9-32. PubMed ID: 6279916.
    Abstract:
    Ceftizoxime, a new cephalosporin preparation, was evaluated for its antibacterial activity, absorption, excretion and clinical effectiveness, and the following results were obtained. The minimum inhibitory concentrations (MICs) of ceftizoxime against 211 clinical isolates were determined in comparison with those of cefazolin, cefmetazole, cefotiam and 6059 S. Against S. pyogenes (50 strains), ceftizoxime was 1 tube inferior to cefazolin inoculum size of 10(8) cells/ml, but was 2--3 tubes superior to cefmetazole and 6059-S. Against E. coli (50 strains), ceftizoxime and 6059-S were significantly more active than the other drugs. The susceptibility pattern of Klebsiella sp. (50 strains) to ceftizoxime was similar to that to cefotiam and 6059-S. Against Proteus sp. (50 strains), cefotiam and 6059-S were more active than the other drugs. Ceftizoxime was intermediate in activity, and cefazolin was the least active. Against H. influenzae (11 strains), ceftizoxime was the most active, with concentrations of 0.1 mcg/ml required to inhibit 100% of strains with an inoculum size of 10(8) cells/ml and 10(6) cells/ml. A dose of ceftizoxime 10 mg/kg or 20 mg/kg was administered to 15 patients aged from 5 years to 12 years, and serum levels and urinary excretion of the drug were measured. Intravenous bolus injection of the drug in dose of 10 mg/kg and 20 mg/kg yielded mean serum levels of 26.6 mcg/ml and 55.7 mcg/ml at 30 minutes, respectively. The serum levels of the drug, thereafter, declined gradually but still remained 1.3 mcg/ml and 2.7 mcg/ml at 6 hours. The serum half-lives (T 1/2) were estimated to be 1.17 hours in dose of 10 mg/kg and 1.31 hours in dose of 20 mg/kg. When a dose of 20 mg/kg was infused over a period of 30 minutes, the serum levels attained the peak of 72.4 mcg/ml to 82.4 mcg/ml (mean 79.4 mcg/ml) at the end of infusion. The levels, thereafter, tapered to mean levels of 45.3 mcg/ml at 30 minutes, 24.7 mcg/ml at 1 1/2 hours, and 3.6 mcg/ml at 5 1/2 hours, with a T 1/2 of 1.22 hours. Meanwhile, when the same dose was infused over 1 hour, the serum levels attained the peak of 59.4 mcg/ml to 68.5 mcg/ml (mean 64.2 mcg/ml). The mean serum levels after the end of infusion were 41.3 mcg/ml at 30 minutes, 21.6 mcg/ml at 1 hour and 1.9 mcg/ml at 5 hours, with a T 1/2 of 0.97 hours. Urinary recovery of the drug was 69.2% to 79.9% after intravenous injection and 62.3% to 79.9% after drip infusion, most of the given drug was excreted in the first 2 hours after administration. In our clinical study, 27 children with moderate or severe infections (12 cases of bronchopneumonia or bronchitis, 5 of pyelonephritis, 3 of purulent meningitis, etc.) were treated with ceftizoxime at the daily dose of 30--309 mg/kg for 3--23 days. Clinical response was excellent in 10, good in 9, fair in 5 and poor in 3. The drug was proved to be very effective against infections due to H. influenzae K. pneumoniae, E. coli and S. aureus. No serious side effects were observed in any case.
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