Bacteriological, pharmacokinetic and clinical evaluations of ceftriaxone in the pediatric field

Ceftriaxone (CTRX), a new injectable cephem antibiotic agent, was evaluated bacteriologically and clinically for its efficacy and safety in the pediatric field by a study group organized with pediatricians from all over the country. The following are a summary of the results of the evaluation. 1. Antibacterial effects: The inhibition of growth was attained for over 90% of strains of K. pneumoniae, H. influenzae and Salmonella spp. at the concentration of 0.10 µg/ml and of strains of S. pneumoniae and E. coli at the concentration of 2.0 µg/ml. The CTRX was proved to have excellent antibacterial effects. 2. Absorption and excretion: Thirty minutes after one shot intravenous administration with 10, 20, 40 and 50 mg/kg of CTRX, its serum levels were 73, 124, 169 and 190 µg/ml, respectively, a clear tendency of dose-response relationship being noticed. The serum levels decreased only gradually and stayed as high as 10 to 20 µg/ml even after 12 hours. The half-lives of the drug were 5.5, 6.3, 6.0 and 4.7 hours for the 4 different dose levels, respectively. Following the intravenous injection with 10, 20 and 40 mg/kg, the urinary excretion rates were 55, 52 and 54%, respectively. Following the one shot intravenous administration or by the drip infusion for 30 minutes with about 50 mg/kg, CTRX levels in the cerebrospinal fluid ranged from 1 to 20.3 µg/ml in case of purulent meningitis (5 to 10 µg/ml in most cases). 3. Clinical results: A total of 322 cases was enrolled. The efficacy of CTRX was evaluated in 295 cases out of the 322, excluding drop-outs and the cases which did not meet the protocols. The clinical efficacy rate was 94% of 191 cases where the causative bacteria were identified, CTRX being “excellent” in 108 cases and “effective” in 72. In the remaining 104 cases where the causative bacteria were not identified, the efficacy rate was 92%, CTRX being “excellent” in 42 cases and “effective” in 54. Furthermore, the efficacy rate was 89% of 18 cases infected with more than one kind of bacteria. The drug showed “excellent” or better effectiveness in 88% of 75 cases which had not responded to other antibiotics. Bacteriologically, 174 out of 216 strains (93%) which were judged to be causative bacteria disappeared with the use of CTRX. Eightyfive percent of 53 strains which had not responded to other antibiotics disappeared by the CTRX treatment. 4. Adverse reactions and over-ranged clinical laboratory parameters: Adverse reactions like diarrhea, loose passage and urticaria appeared in 28 cases out of 322 (8.7%). In clinical laboratory tests, increase in GOT, eosinophilia, increase in GPT, thrombocytosis, etc. were observed in 38 cases (48 symptoms). 5. Optimal clinical dose in children: The optimal clinical dose in children was 20 mg/kg twice a day by intravenous injection or by drip infusion. The dose was adjusted according to types and severities of diseases. The drug was considered to be a useful cephem antibiotic in the pediatric field especially because of the time-saving and cost-effective twice-a-day administration which was enabled due to the fairly long half-life, the broad antibacterial spectrum, the good transfer to the cerebrospinal fluid and the high safety. The administration to newborn babies, once-a-day administration and adverse reactions will have to be studied further for this new antibiotic agent.