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[Fundamental and clinical evaluation on ceftriaxone in the pediatric field]
Insights
Ceftriaxone (CTRX) demonstrates variable antibacterial activity, showing superiority against S. marcescens but potential resistance in some E. coli strains. Its pharmacokinetic profile indicates a long half-life, suggesting sustained therapeutic levels.
Area of Science:
- Pharmacology and Microbiology
- Antibacterial Agents
- Clinical Efficacy
Context:
- Evaluation of ceftriaxone (CTRX), a novel cephalosporin, against clinically relevant bacterial isolates.
- Comparative analysis of CTRX's antibacterial spectrum against established agents like CEZ, CMZ, CTX, and LMOX.
- Assessment of CTRX's pharmacokinetic properties, including serum concentration and half-life following intravenous administration.
Purpose:
- To determine the fundamental and clinical efficacy of ceftriaxone (CTRX).
- To compare the antibacterial activity of CTRX with other cephalosporins against key pathogens.
- To characterize the pharmacokinetic profile of CTRX in humans.
Summary:
- Ceftriaxone (CTRX) exhibited potent activity against S. marcescens, surpassing CEZ, CMZ, CTX, and LMOX. However, it showed less efficacy against S. aureus compared to CMZ and CEZ, and a tendency towards resistance in beta-lactamase producing E. coli and K. pneumoniae.
- Pharmacokinetic studies revealed a mean serum peak of 168.8 mcg/ml after a 40 mg/kg IV injection, with a prolonged half-life of 6.0 hours, among the longest for developing cephalosporins.
- Dose-ranging studies demonstrated a clear dose-response relationship, with higher doses yielding sustained serum concentrations and longer half-lives (4.9-6.2 hours).
Impact:
- Ceftriaxone (CTRX) presents a promising therapeutic option, particularly for infections caused by S. marcescens.
- The observed resistance patterns necessitate careful consideration in treatment strategies for E. coli and K. pneumoniae infections.
- The favorable pharmacokinetic profile of CTRX supports its potential for extended dosing intervals and effective management of various bacterial infections.
Abstract:
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 greater than 100 micrograms/ml with a peak of 3.13 micrograms/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 micrograms/ml or above against 44% of all strains including the beta-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 less than or equal to 0.1, 0.39 and less than or equal to 0.1 microgram/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 micrograms/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 40 mg/kg reached a mean peak of 168.8 micrograms/ml at the first blood sampling (at 30 minutes) and gradually decreased to 137.5 micrograms/ml at 1 hour, 30.9 micrograms/ml at 6 hours, 12.6 micrograms/ml at 12 hours and 3.8 micrograms/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 20 mg/kg and 40 mg/kg revealed that the former group reached a peak of 85.4 micrograms/ml at the termination of drip while the latter's peak was 176.6 micrograms/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 micrograms/ml at 6 hours, 5.1 and 15.0 micrograms/ml at 12 hours, and 1.6 and 4.1 micrograms/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.(ABSTRACT TRUNCATED AT 400 WORDS)