CEFTRIAXONE IN NEONATES AND YOUNG INFANTS; CLINICAL EFFICACY, PHARMACOKINETIC EVALUATION AND EFFECT ON THE INTESTINAL BACTERIAL FLORA

• Published in: Japanese journal of antibiotics 1988/02/25, Vol.41(2), pp.117-127
• Main Authors: FUJITA, KOZO, MURONO, KO-ICHI, SAKATA, HIROSHI, KAKEHASHI, HITOSHI, OKA, TOSHIAKI, KAERIYAMA, MASATO, YOSHIOKA, HAJIME, MARUYAMA, SHIZUO, SANAE, NOBUTAKA, INYAKU, FUMIE
• Format: Article
• Language: Japanese
• Subjects: Birth Weight; Ceftriaxone - pharmacokinetics; Ceftriaxone - therapeutic use; Female; Humans; Infant; Infant, Newborn; Injections, Intravenous; Intestines - microbiology; Male; Sepsis - drug therapy; Sepsis - metabolism; Sepsis - microbiology
• ISSN: 0368-2781; 2186-5477
• DOI: 10.11553/antibiotics1968b.41.117

Twenty-two newborn and young infants, including 13 premature infants, were treated with ceftriaxone (CTRX) and the clinical efficacy and side effects were evaluated. Ages of the patients ranged from 0 to 106 days, and their body weights from 1.19 to 3.92kg. Dose levels were 15 to 23mg/kg every 12 to 24 hours for 2 to 13.5 days. Eighteen infants with sepsis and 1 infant with purulent coxitis were considered to have responded to the CTRX treatment. The results were excellent in 13 and good in 6 patients. The drug was well tolerated, although diarrhea occurred in 2 patients, eosinophilia in 6 patients, slightly elevated serum concentrations of transaminases in 2 patients and thrombocytosis in 1 among the 22 patients. The pharmacokinetic studies on CTRX were done in 8 patients including 3 premature infants. The ages ranged from 3 to 50 days, and body weight from 2.20 to 3.94kg. Plasma concentrations 30 minutes after single 10mg/kg intravenous bolus injection in two 4-to 5-day-old premature neonates were 48.4 and 50.0μg/ml and those at 6 hours were 22.7 and 23.4μg/ml, respectively. In 2 mature neonates, plasma levels were 42.2 and 39.1μg/ml at 30 minutes and 23.4 and 26.6μg/ml at 6 hours after single 20mg/kg doses. In four 12-to 50-day-old patients, plasma concentrations ranged from 35.9 to 175.0μg/ml at 30 minutes and from 21.9 to 32.8μg/ml at 6 hours after multiple doses of 20mg/kg intravenous bolus injection. The plasma half-lives of the drug ranged from 6.6 to 16.8 hours in these 8 patients. Excretion rates of this drug into urine within 12 hours were 21.4 to 63.4% in 7 patients. Urine concentrations of the drug in 34 samples collected at various times from the 7 patients ranged from 28.3 to 469.0μg/ml. The cerebrospinal fluid level at 2 hours after a dose was 3.33μg/ml on the 5th day of treatment in 1 patient with sepsis receiving 18mg/kg of the drug every 12 hours. Its level at 3 hours after a dose was 6.07μg/ml on the 6th day of treatment in another patient with aseptic meningitis receiving 20mg/kg every 12 hours. The influence of CTRX on the fecal flora was studied in 3 patients receiving 20mg/kg×2/day.The characteristic pattern observed during the drug administration was the disappearance of Bifidobacterium and Enterobacteriaceae, the preservation of Streptococcus and Staphylococcus, and the increase in Candida. The antibiotic concentrations were from 12 to 210μg per g of wet feces. On the 5th day after cessation of the drug administration, considerabl