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[Fundamental and clinical evaluation of ceftriaxone in the pediatric field]
Insights
Ceftriaxone (CTRX) demonstrates excellent pediatric antibacterial activity against key pathogens like H. influenzae and S. pyogenes, with favorable serum and CSF levels. However, its efficacy is limited against S. aureus and P. aeruginosa.
Area of Science:
- Pharmacology and Microbiology
- Pediatric Infectious Diseases
Context:
- Evaluation of ceftriaxone (CTRX) in pediatric patients.
- Assessment of antibacterial spectrum and pharmacokinetic properties.
Purpose:
- To determine the fundamental and clinical efficacy of ceftriaxone in pediatric applications.
- To compare CTRX's antibacterial activity with other cephalosporins.
Summary:
- Ceftriaxone exhibits potent activity against Streptococcus pyogenes, Escherichia coli, Klebsiella pneumoniae, and Haemophilus influenzae, with MIC80 values below 0.20 µg/ml.
- While less effective against Staphylococcus aureus and Pseudomonas aeruginosa, CTRX shows superior activity against H. influenzae compared to other tested cephalosporins.
- Pharmacokinetic studies reveal a mean serum half-life of 5.92 hours and significant concentrations in cerebrospinal fluid, indicating potential utility in meningitis treatment.
Impact:
- Provides crucial data on ceftriaxone's spectrum of activity and pharmacokinetic profile in pediatric populations.
- Informs clinical decision-making for antibiotic selection in children, particularly for infections caused by susceptible Gram-negative and Gram-positive bacteria.
- Highlights the need for susceptibility testing for S. aureus and P. aeruginosa when considering CTRX therapy.
Abstract:
Fundamental and clinical evaluation of ceftriaxone (Ro 13-9904, CTRX) was performed in the pediatric field. Antibacterial activity The MIC80 of CTRX against clinical isolates such as S. aureus (23 strains), S. pyogenes (23 strains), E. coli (20 strains), K. pneumoniae (23 strains), H. influenzae (15 strains) and P. aeruginosa (23 strains) were 6.25 micrograms/ml, 0.024 microgram/ml, 0.20 microgram/ml, 0.05 microgram/ml, less than or equal to 0.006 microgram/ml and 12.5 micrograms/ml, respectively. The antibacterial activity of CTRX was therefore poor against S. aureus and P. aeruginosa, but quite excellent against S. pyogenes, E. coli, K. pneumoniae and H. influenzae. Compared with cefotaxime (CTX), cefoperazone (CPZ), cefmetazole (CMZ), cefazolin (CEZ) and ceftazidime (CAZ), CTRX was the highest in the antibacterial activity against H. influenzae, next to CTX against S. pyogenes, E. coli and K. pneumoniae, similar to CTX, CPZ and CAZ against S. aureus and similar to CTX against P. aeruginosa. Absorption, Excretion The mean serum levels of CTRX after an intravenous one shot injection with about 20 mg/kg in 3 children aged 10 to 14 years were 160.0 +/- 23.3 micrograms/ml after 1/4 hour, 134.3 +/- 27.5 micrograms/ml after 1/2 hour, 115.0 +/- 33.2 micrograms/ml after 1 hour, 95.3 +/- 28.4 micrograms/ml after 2 hours, 75.3 +/- 14.5 micrograms/ml after 4 hours, 30.3 +/- 13.5 micrograms/ml after 12 hours and 8.2 +/- 3.1 micrograms/ml after 24 hours, while the half-life time was 5.92 +/- 0.43 hours on the average. The mean urinary levels were 1,060 +/- 461 micrograms/ml from 0 to 2 hours, 309 +/- 122 micrograms/ml from 2 to 4 hours, 375 +/- 83 micrograms/ml from 4 to 6 hours, 237 +/- 77 micrograms/ml from 6 to 12 hours and 122 +/- 23 micrograms/ml from 12 to 24 hours, the mean urinary recovery rate up to 24 hours being 38.9 +/- 13.6%. The concentration in the cerebrospinal fluid The mean levels of CTRX in the cerebrospinal fluid of the patients with purulent meningitis were 4.30 +/- 4.22 micrograms/ml 1 hour after an intravenous one shot injection with 42 to 51 mg/kg, 4.64 +/- 3.53 micrograms/ml after 3 1/2 hours to 6 hours, 3.79 +/- 2.15 micrograms/ml after 7 1/2 hours to 12 hours and 1.79 +/- 0.23 microgram/ml after 19 hours.(ABSTRACT TRUNCATED AT 400 WORDS)