Meningitic Dose of Meropenem According to Mandell Guidelines
The meningitic dose of meropenem is 2 grams intravenously every 8 hours, administered as a 15-30 minute infusion or 3-5 minute bolus injection. 1
FDA-Approved Dosing for Bacterial Meningitis
The FDA label specifies meropenem dosing for bacterial meningitis in pediatric patients 3 months and older:
- For pediatric patients weighing over 50 kg: 2 grams every 8 hours 1
- For pediatric patients under 50 kg: 40 mg/kg every 8 hours (maximum 2 grams) 1
- Administration: Can be given as a 15-30 minute infusion or as a 3-5 minute bolus injection 1
Contemporary Guideline Recommendations
While the FDA label provides the official dosing, recent guidelines from the Journal of Infection align with this approach:
- For suspected ESBL-producing organisms causing meningitis: 2 grams IV every 8 hours 2, 3
- Treatment duration for Enterobacteriaceae meningitis: 21 days 2
Clinical Evidence Supporting This Dose
The 2 gram every 8 hours regimen is supported by multiple lines of evidence:
- Historical validation: A 1995 randomized trial used meropenem 40 mg/kg every 8 hours (maximum 6 grams/day) in adults with bacterial meningitis, achieving 100% clinical cure rates 4
- CSF penetration data: A 2017 study demonstrated that 2 grams every 8 hours achieves peak CSF concentrations of 2.4 ± 0.3 mg/L with 17.6% CSF penetration 5
- Pharmacokinetic optimization: A 2016 population pharmacokinetics study recommended 2 grams every 8 hours as a 4-hour infusion for optimal CSF exposure, particularly when CSF drainage is less than 150 mL/day 6
Important Dosing Considerations
Renal adjustment is critical to prevent neurotoxicity:
- CrCl 26-50 mL/min: Administer recommended dose every 12 hours 1
- CrCl 10-25 mL/min: Administer one-half recommended dose every 12 hours 1
- CrCl <10 mL/min: Administer one-half recommended dose every 24 hours 1
Common Pitfalls to Avoid
- Underdosing in meningitis: The meningitic dose (2 grams every 8 hours) is higher than the standard sepsis dose (1 gram every 8 hours) due to limited CSF penetration 3, 7
- Failure to adjust for renal impairment: Meropenem accumulation in renal dysfunction significantly increases seizure risk 3
- Using meropenem as first-line for typical meningococcal infections: Third-generation cephalosporins (ceftriaxone/cefotaxime) remain preferred for meningococcal disease, as meropenem offers no advantage 3
- Inadequate treatment duration: Gram-negative meningitis typically requires 21 days of therapy, not the shorter courses used for other pathogens 2
Extended Infusion Strategy
For organisms with higher MICs or when optimizing pharmacodynamics: