Clinical Pharmacology of Cefotaxime in Neonates and Infants: Effects and Pharmacokinetics

Authors

Via San Andrea 32, 56127 Pisa, Italy.

Abstract

Cefotaxime is a bactericidal "third generation" cephalosporin has a broad-spectrum activity against gram-positive microorganisms and exceptional activity against most gram-negative microorganisms. Cefotaxime is widely considered to be the antibiotic of choice for the management of neonatal meningitis and sepsis caused by gram-negative bacteria. Cefotaxime is active against Neisseria meningitis, Streptococcus pneumoniae, Haemophilus influenzae, Salmonella specimens, Staphylococcus, Enterobacter species, Haemophilus parainfluenzae, Pseudomonas aeruginosa, Escherichia coli, Citrobacter freundii, and Klebsiella pneumoniae. In neonates, the recommended dose of cefotaxime is 25 mg/kg every 6 hours by intravenous or intramuscular administration. Some authors administered cefotaxime at a daily dose of 150 or 300 mg/kg. After the intravenous administration of 50 mg/kg cefotaxime every 6 hours, the serum concentrations of this antibiotic are 56.9+28.7 µg/ml at 1 hour and 3.66+5.65 µg/ml at 6 hours after the administration. The cerebrospinal fluid concentration of cefotaxime, measured 1 hour after the intravenous administration of 50 mg/kg cefotaxime, is 3.72+5.57 µg/ml. The MIC50 (µg/ml) and the MBC50 (µg/ml) are 0.024+0.026 and 0.064+0.054, respectively, for Haemophilus influenzae, 0.062+0.034 and 0.240+0.027, respectively, for Streptococcus pneumoniae and 0.057+0.088 and 0.283+0.44, respectively, for Neisseria meningitis. In neonates, the half-life of cefotaxime is 2 to 6 hours, it varies with gestational and postnatal ages, and the clearance and distribution volume are 0.074+0.03 l/h/kg and 0.461+0.027 l/kg, respectively. Cefotaxime diffuses in tissues and penetrates into the cerebrospinal fluid. This antibiotic is safe and well tolerated in neonates. The aim of this study is to review the effects and pharmacokinetics of cefotaxime in neonates and infants.

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