Clinical Pharmacology of Ceftazidime in Neonates: Effects and Pharmacokinetics

Ceftazidime is a valuable third-generation bactericidal cephalosporin. Ceftazidime inhibits the biosynthesis of bacterial cell peptidoglycan, causing inhibition of bacterial growth or cell lyses and death. Common nosocomial gram-negative organisms susceptible to ceftazidime include Escherichia coli, Haemophilus influenzae, Klebsiella pneumoniae, Neisseria, Moraxella catarrhalis, Proteus mirabilis, Proteus vulgaris, and Providencia stuartii. Good activity remains against other gram-negative species including Salmonella, Shigella, and Neisseria species. Ceftazidime is widely distributed in most body tissues and fluids including respiratory secretion, ascitic fluid and cerebrospinal fluid. Ceftazidime is administered parenterally, is completely absorbed after intramuscular injection, and peak drug concentrations generally occur within 3 hours of intramuscular injection. Ceftazidime is not absorbed when taken by mouth. Ceftazidime half-life is 4 to 10 hours at birth, but half this in infants more than a week old. In premature infants, the distribution volume and the clearance of ceftazidime range from 292+44 to 366+130 ml/kg and from 27.8+5.8 to 60.8+8.3 ml/h/kg, respectively. Ceftazidime binds to plasma proteins at 10% to 17%. No ceftazidime metabolites have been identified and this drug is excreted by renal elimination. The dose of ceftazidime is 25 mg/kg once-daily in the first week of life. Ceftazidime crosses the placenta freely, but there is no evidence of teratogenicity. As empirical ceftazidime monotherapy may not be appropriate for the treatment of neonatal sepsis, the addition of ampicillin, to cover against enterococci and Listeria monocytogenes, seems prudent in these neonatal patients. The aim of this study is to review the effects of ceftazidime in neonates.