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

Ceftriaxone is a versatile and useful "third-generation" cephalosporin that needs to be administered once-daily. Ceftriaxone is a β-lactamase-resistant cephalosporin. It is active against important gram-positive and most gram-negative bacteria. The MIC90s of ceftriaxone are 0.1 µg/ml for Escherichia coli, 0.1 µg/ml for Klebsiella species, 0.2 µg/ml for Proteus species, 0.3 µg/ml for Enterobacter species, 0.4 µg/ml for Serratia species, 0.06 µg/ml for Streptococcus agalactiae, and 2 µg/ml for Staphylococcus aureus (β-lactamase producers). Ceftriaxone, like other cephalosporins, kills bacteria by interfering with the synthesis of cell walls. Ceftriaxone has a good penetration into the cerebrospinal fluid and is useful in the treatment of meningitis sustained by susceptible bacteria. The dose of ceftriaxone is 50 mg/kg per day in neonates and 100 mg/kg per day in older infants. Ceftriaxone has a longer half-life than other cephalosporins; the plasma half-life of ceftriaxone is 15 hours at birth and 7 hours over 2-4 weeks.
The mean distribution volume of ceftriaxone ranges from 0.497 to 0.608 l/kg, and is not different in neonates and infants. In neonates, the total body clearance is 0.28 ml/min/kg after single administration and 0.41 to 0.54 ml/min/kg after multiple ceftriaxone administrations. After single intramuscular administration of ceftriaxone, the time to reach the peak plasma concentration is 1.8 hours. This antibiotic displaces bilirubin from albumin binding sites, thereby increasing the amount of free bilirubin in plasma. Ceftriaxone should not be administered to infants with hyperbilirubinemia. The aim of this study is to review the effects and pharmacokinetics of ceftriaxone in neonates.