Clinical Pharmacology of Meropenem in Neonates: Effects and Pharmacokinetics

Meropenem, a carbapenem antibiotic, has a broad-spectrum activity and is active against Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influencae, Moraxella catarrhalis, gram-negative enteric bacilli as Escherichia coli, Klebsiella, Enterobacter, Serratia and Pseudomonas aeruginosa. Meropenem has excellent penetration in body tissues and in cerebrospinal fluid (in the presence of inflammation). Meropenem is bactericidal, because it inhibits transpeptidases responsible for peptidoglycan synthesis involved in cell formation and repair.
Meropenem is approved for use in complicated intraabdominal infections, complicated skin and skin structure infections and bacterial meningitis in pediatric patients. The dose of meropenem is 20 mg/kg by slow intravenous infusion once every 12 hours in the first week of life and once every 8 hours for infants older than this. Meropenem is predominantly excreted by renal route. After an administration of 15 mg/kg meropenem twice-daily to premature infants, the mean total body clearance is 0.157 l/kg/h, the distribution volume is 0.74 l/kg, and the half-life is 3.4 hours. The %T>MIC is the percent time above minimum inhibitory concentration. After a dose of 20 mg/kg t.i.d., the target value of 50%T>MIC is achieved, indicating that 20 mg/kg is effective for susceptible bacteria. In contrast, for bacteria with higher MIC such as Pseudomonas aeruginosa (MIC ≥2 µg/ml), the probability of target attainment of 50%T>MIC is 60.7% at a dose of 40 mg/kg t.i.d. The limited amounts of meropenem that cross the placenta are insufficient to treat infection in fetuses. The aim of this study was to review the effects and pharmacokinetics of meropenem in neonates.