Fundamental and clinical studies were made on cefuroxime, a new cephalosporin, and the following results were obtained.
(1) Antibacterial activity of the drug against 15 strains of
Staphylococcus aureus was almost equal to that of cefazolin. Although cefazolin was superior against 33 strains of E. coli to cefuroxime, the latter tended to have a higher antibacterial activity against the strains with higher MIC to cefazolin. Based on the studies with 6 strains of
Klebsiella pneumoniae, 43 of
Klebsiella oxytoca and 12 of
Proteus, it was suggested that cefuroxime was more stable to β-lactamase than cefazolin. Both cefuroxime and cefazolin had MICs of more than 100μg/ml against 3 strains of Enterobacter, 2 of
Citrobacter and 9 of
Pseudomonas aeruginosa.
(2) Passage of the drug into the cerebrospinal fluid (CSF) was evaluated in experimental staphylococcal meningitis in rabbits. The average maximal CSF concentration of the drug in 4 rabbits was 2.90±0.75μg/ml (45 minutes after a one-shot intravenous injection of 100mg/kg). The area under the curve (AUC) of the CSF concentration up to 3 hours was 282.08 min ·μg/ml, CSF/serum ratio of the AUC 12.6%, and T1/2 of the CSF concentration 69.1 minutes which was 3.31 times as high as that of the blood, respectively. The longer T1/2 of the CSF appeared to be the merit of cefuroxime.
(3) Two children received a single intravenous drip infusion of the drug, 26.8 mg/kg and 29.1 mg/kg, respectively, over a30-minute period and the blood concentrations determined. They were highest at the end of the infusion,
i.e., 55μg/ml and 105μg/ml, declined rapidly thereafter, and were 0.82μg/ml and 1.45μg/ml 4 hours after the end of the infusion, T1/2 being 41.1 minutes and 41.7 minutes, respectively.
(4) Four children, each two of pneumonia and empyema, were treated with71.4-87.2 mg/kg of the drug by a 30-minute drip infusion divided in three doses. An overallefficacy rate was 75%,
i.e., excellent in two cases of pneumonia, good in one case of empyema and failure in another case of empyema.
(5) One patient with empyema initially complained of a vascular pain by one-shot intravenous injection but offered no complaints when it was switched to a 30-minute drip infusion. Except for this, no adverse reactions related to cefuroxime injection were recognized.
(6) Based on the above results, it was concluded that cefuroxime is a potent new antibiotic in the treatment of respiratory tract infection in children. Pharmacokinetic studies also suggested its usefulness in urinary tract infection. Based on the studies on experimental meningitis in rabbits, cefuroxime was expected to be a potent antibiotic in the treatment of ampicillin-resistant
Haemophilus influenzae meningitis but further investigations will be required to establish its indication.
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