What is the recommended dose of meropenem (Merrem) for treating meningitis in neonates?

Meropenem Dosing for Neonatal Meningitis

For neonatal meningitis, meropenem should be dosed at 40 mg/kg every 8 hours for most neonates, with age-specific adjustments required for premature and very young infants. 1

Critical Context: Meropenem Is Not First-Line Therapy

• Meropenem is NOT the guideline-recommended empiric treatment for neonatal meningitis. 1
• The Pediatric Infectious Diseases Society and American Academy of Pediatrics recommend ampicillin plus cefotaxime (or ampicillin plus an aminoglycoside) as first-line therapy for neonates <1 month old with meningitis. 1
• Reserve meropenem for specific circumstances only: confirmed multidrug-resistant Gram-negative organisms, failure of first-line therapy, or known colonization with resistant organisms in the NICU setting. 1
• The FDA label explicitly states meropenem is indicated for bacterial meningitis only in pediatric patients ≥3 months of age, not neonates. 2

Age-Specific Dosing Algorithm for Neonatal Meningitis

When meropenem is clinically indicated for neonatal meningitis, use the following gestational age (GA) and postnatal age (PNA) based dosing:

For Premature Neonates (<32 weeks GA):

• PNA <14 days: 20 mg/kg every 12 hours 1
• PNA ≥14 days: 20 mg/kg every 8 hours 1

For Term/Near-Term Neonates (≥32 weeks GA):

• PNA <14 days: 20 mg/kg every 8 hours 1
• PNA ≥14 days: 30 mg/kg every 8 hours 1

For CNS Infections Requiring Maximum Penetration:

• 40 mg/kg every 8 hours is recommended by the Infectious Diseases Society of America for serious CNS infections, based on pharmacokinetic modeling demonstrating the need for higher CNS penetration. 1

Administration Details

• Infusion time: Administer as a 30-minute intravenous infusion. 2
• Prolonged infusion consideration: While one study showed 4-hour infusions improved plasma target attainment and reduced mortality in neonatal sepsis 3, CSF penetration is actually worsened with prolonged infusions. 4
• For meningitis specifically, standard 30-minute infusions are preferred to optimize CSF concentrations, despite lower plasma time above MIC. 4

Duration of Therapy

• Minimum 14-21 days for Gram-negative meningitis, as recommended by the Infectious Diseases Society of America. 1

Important Clinical Caveats

CSF Penetration Limitations:

• Meropenem CSF penetration is low (approximately 8% of plasma concentrations), though this increases with elevated CSF protein levels (up to 40% penetration at CSF protein of 6 g/L). 4
• This limited penetration underscores why higher doses (40 mg/kg) are necessary for meningitis versus other infections. 1

Renal Function Considerations:

• Dose adjustments are necessary in very low birth weight neonates (<2000 g). 1
• Meropenem clearance is substantially influenced by estimated creatinine clearance and increases with postnatal age and gestational age. 5, 6
• The pharmacokinetic formula: CL (L/h/kg) = 0.041 + 0.040/SCr + 0.003 × (PCA-35), where PCA is postconceptional age. 5

Safety Profile:

• Prolonged infusions (4 hours) were associated with significantly less acute kidney injury compared to conventional 30-minute infusions in one neonatal study. 3
• No significant adverse effects were reported in pediatric pharmacokinetic studies. 7

Monitoring Requirements:

• Monitor renal function closely, particularly in premature neonates and those with changing creatinine clearance. 5, 6
• Ensure adequate duration of therapy (14-21 days minimum) to prevent relapse. 1