1981 年 34 巻 6 号 p. 946-954
The bacteriological and pharmacokinetic properties of cefotaxime, including antibacterial spectrum and activity and CSF penetration in animals, suggested that this compound may beclinically effective in the treatment of purulent meningitis in children. The safety and effectiveness of cefotaxime were therefore evaluated in a multicenter clinical trial carried out by the Pediatrics Research Group (Chairman: Prof. RYOCHI FUJII).
Seventeen children with purulent meningitis were treated with cefotaxime. Four patients were aged less than 3 months, 5 from 3 to 12 months, and 8 from 1 to 3 years. The causative organisms were S. epidermidis, α-Streptococcus, S. pneumoniae and H. parainfluenzae in 1 patient each, H. influenzae in 5 patients, E. coli in 2 patients, and unknown in 6 patients.
Cefotaxime was administered in a dose of about 50 mg/kg 4 to 6 times daily in 14 patients. The route of administration was intravenous bolus injection or 30-minute to 1-hour intravenous drip infus on in the majority of patients. The duration of treatment ranged from 7 to 35 days with a mean of 17 days.
The therapeutic efficacy of cefotaxime was evaluated to be excellent in 10 patients, good in 5 patients, and failure in 2 patients for a responder rate of 88.2%. The 2 failures suffered from S. epidermidis and α-Streptococcus meningitis in association with a CSF shunt. Among the 15 cefotaxime responders, sequelae consisted of subdural effusion in 2 patients and cerebral palsy in 1 patient. The clinical condition of all 3 of these patients was severe and the initiation of treatment delayed. Sequelae were not noted in the other 12 patients. Eight laboratory abnormalities attributed to cefotaxime, consisting of 2 instances of eosinophilia, 4 elevations of GOT, and 2 elevations of GPT, were seen in 5 patients. All abnormalities were transient and not severe enough to warrant withdrawal of the drug.
CSF concentrations of cefotaxime, determined 26 times after a 50 mg/kg intravenous bolus injection or 30-minute intravenous drip infusion in 5 patients ranged from a minimum of 1.0μg/ml to a maximum of 13.2μg/ml. Penetration to the CSF tended to decrease as the patient showed signs of recovery from meningitis, but concentrations of ≥4μg/ml, sufficiently above the MICs of causative organisms, were seen in most patients during the first week of treatment. CSF con-centrations of ampicillin were determined in 2 patients after a single 77 mg/kg intravenous bolus injection. In both patients ampicillin levels were lower than those seen after a 50 mg/kg intravenous dose of cefotaxime.
Considering that cefotaxime is at least comparable to or superior to ampicillin in terms of antibacterial activity against group B Streptococcus and E. coli, and H. influenzae and S. pneumoniae, the major pathogens during neonatal and subsequent stages respectively, including ampicillin-resistant strains, the above results strongly suggest that cefotaxime should be the drug of choice for the treatment of purulent meningitis in neonates, infants, and older children.
