Meropenem Dosing in Meningitis with Creatinine 2.37 mg/dL
For meningitis with a creatinine of 2.37 mg/dL (estimated CrCl 26-50 mL/min), reduce the standard meropenem dose of 2g every 8 hours to 2g every 12 hours, administered as a 30-minute to 2-hour infusion. 1
Calculating Creatinine Clearance
- Use the Cockcroft-Gault equation to estimate creatinine clearance when only serum creatinine is available 1:
- Males: CrCl (mL/min) = [Weight (kg) × (140 - age)] / [72 × serum creatinine (mg/dL)]
- Females: 0.85 × above value
- With a creatinine of 2.37 mg/dL, most adult patients will fall into the 26-50 mL/min or 10-25 mL/min range depending on age and weight 1
Renal Dose Adjustment Algorithm
The FDA-approved dosing for renal impairment follows this structure 1:
- CrCl >50 mL/min: 2g every 8 hours (standard meningitis dose)
- CrCl 26-50 mL/min: 2g every 12 hours (recommended dose maintained, interval extended)
- CrCl 10-25 mL/min: 1g every 12 hours (half the recommended dose)
- CrCl <10 mL/min: 1g every 24 hours (half the recommended dose)
Administration Details
- Administer as an intravenous infusion over 30 minutes for meningitis patients 1, 2
- When individual doses exceed 1g, extend the infusion period to 1.5-2 hours to reduce seizure risk 3
- For optimal CSF penetration, consider prolonged infusion of 4 hours if feasible, particularly when CSF drainage is minimal 2
Critical Monitoring Requirements
Renal impairment is the primary risk factor for meropenem-induced neurotoxicity due to drug accumulation 4, 5:
- Monitor for neurological manifestations including acute confusional state, encephalopathy, myoclonus, and seizures 5
- Trough concentrations >64 mg/L are associated with neurotoxicity in 50% of patients 4, 5
- Therapeutic drug monitoring (TDM) should be strongly considered in patients with renal impairment to prevent excessive plasma concentrations 5, 6
- Target serum concentrations of 20-30 mg/L when using TDM-guided dosing 6
CSF Penetration Considerations
- Meropenem CSF penetration is approximately 15% of serum concentrations in ventriculitis patients 6
- Initial dosing based on renal function typically achieves CSF concentrations >1 mg/L in most patients 6
- CSF drainage volume significantly affects CSF drug concentrations—higher drainage (>150 mL/day) reduces CSF levels 2
- For optimal CSF target attainment (≥50% of dosing interval above MIC), a 4-hour infusion provides superior PTA compared to shorter infusions 2
Treatment Duration
- 21 days for Enterobacteriaceae meningitis 7
- 10-14 days for pneumococcal meningitis (10 days if stable response, up to 14 days if slow response) 4
- 5 days for meningococcal infections (though ceftriaxone remains first-line for this pathogen) 4
Common Pitfalls to Avoid
- Do not use standard dosing (2g every 8 hours) without renal adjustment—this significantly increases neurotoxicity risk in patients with elevated creatinine 5, 1
- Avoid short infusion times (<30 minutes) in renally impaired patients—prolonged infusions reduce peak concentrations and seizure risk 3, 2
- Do not assume adequate CSF penetration without monitoring—only 15% of serum levels reach CSF, and high CSF drainage further reduces this 6, 2
- Meropenem has a relative pro-convulsive activity of 16% compared to penicillin G, making dose adjustment critical to prevent seizures 4, 5
- If neurological symptoms develop during therapy, immediately suspect drug toxicity and consider dose reduction or discontinuation 5
When Meropenem is Appropriate for Meningitis
Meropenem is indicated for 4, 7:
- Gram-negative bacilli meningitis with suspected ESBL-producing organisms
- Post-neurosurgical meningitis with resistant pathogens
- Infections caused by Enterobacter, Citrobacter, or Serratia species
Meropenem offers no advantage over ceftriaxone/cefotaxime for typical meningococcal or pneumococcal meningitis and should not be used as first-line therapy in these cases 4, 7.