FUNDAMENTAL AND CLINICAL EVALUATION ON CEFTRIAXONE IN THE PEDIATRIC FIELD

• Published in: Japanese journal of antibiotics 1984/11/25, Vol.37(11), pp.2060-2082
• Main Authors: TOYONAGA, YOSHIKIYO, KUROSU, YOSHIIE, UEKUSA, TADASHI, NAKAMURA, HIRONORI, SUGITA, MORIMASA, OKABE, TAKESHI, KAWAMURA, KENICHI, SEO, KIWAMU, TAKAHASHI, TAKAYUKI, HORI, MAKOTO
• Format: Article
• Language: Japanese
• Subjects: Bacteria - drug effects; Bacterial Infections - drug therapy; Cefotaxime - analogs & derivatives; Cefotaxime - metabolism; Cefotaxime - pharmacology; Cefotaxime - therapeutic use; Ceftriaxone; Child; Child, Preschool; Drug Evaluation; Drug Resistance, Microbial; Female; Humans; Infant; Male
• ISSN: 0368-2781; 2186-5477
• DOI: 10.11553/antibiotics1968b.37.2060

Fundamental and clinical evaluation on ceftriaxone (Ro 13-9904, CTRX) was performed. CTRX was compared with CEZ, CMZ, CTX and LMOX in the antibacterial activity against the clinical isolates such as S. aureus, E. coli, P. mirabilis, K. pneumoniae and S. marcescens. Against S. aureus, the MIC of CTRX ranged from 0.2 to > 100 μg/ml with a peak of 3.13 μg/ml, showing that CTRX was almost equal to CTX in activity, slightly superior to LMOX and much inferior to CMZ and CEZ, although some strains were not susceptible to CEZ. Against the intestinal strains of E. coli, K. pneumoniae and P. mirabilis, the MIC distribution of CTRX was similar to that of CTX and LMOX while CTRX showed the MIC as high as 3.13 μg/ml or above against 44% of all strains including the β-lactamase producing strains of E. coli and K. pneumoniae, indicating a slight tendency of their becoming resistant. The MIC peaks against E. coli, K. pneumoniae and P. mirabilis were ≤ 0.1, 0.39 and ≤ 0.1 μg/ml, respectively. As to S. marcescens which is drawing attention as a causative agent for infections inside of hospitals or those among young infants, CTRX inhibited 84% of the strains at 3.13 μg ml, showing a definite superiority to CEZ and CMZ and a slight superiority to CTX and LMOX. The serum concentration after a single intravenous injection with 40mg/kg reached a mean peak of 168.8 μg/ml at the first bloodsampling (at 30 minutes) and gradually decreased to 137.5 μg/ml at 1 hour, 30.9 μg/ml at 6 hours, 12.6 μg/ml at 12 hours and 3.8 μg/ml at 24 hours, while the half-life time was 6.0 hours. The comparison of the serum level by 1 hour intravenous drip infusion between the dosage groups of 20mg/kg and 40mg/kg revealed that the former group reached a peak of 85.4 μg/ml at the termination of drip while the latter's peak was 176.6 μg/ml observed during the drip (30 minutes after the initiation of drip). The respective levels of the 2 groups were 15.4 and 32.1 μg/ml at 6 hours, 5.1 and 15.0 μg/ml at 12 hours, and 1.6 and 4.1 μg/ml at 24 hours, indicating a distinct dose-response 2 hours after the initiation of drip administration. The half-life times were 4.9 and 6.2 hours, respectively, which are the longest among the cephalosporins presently being developed. The urinary recovery rates evaluated in 11 cases were similar to those of other cephalosporins, ranging from 44.5 to 76.8%. The levels of CTRX in the cerebrospinal fluid (CSF) of 2 children with meningitis, unlike other cephalosporins, showed only