Renal Dose Adjustment of Meropenem in Acute Bacterial Meningitis
For acute bacterial meningitis caused by Enterobacteriaceae or suspected ESBL organisms, administer meropenem 2 grams IV every 8 hours with mandatory dose reduction when creatinine clearance falls below 50 mL/min to prevent neurotoxicity while maintaining adequate CSF concentrations. 1, 2
Standard Dosing for Bacterial Meningitis
- Initial empiric dose: Meropenem 2 grams IV every 8 hours is the recommended regimen for suspected ESBL-producing Enterobacteriaceae or gram-negative bacilli causing meningitis 1, 3
- Infusion duration: Extend infusion to 1.5-2 hours when individual doses exceed 1 gram to reduce seizure risk 2
- Treatment duration: Continue for 21 days when Enterobacteriaceae is confirmed as the causative pathogen 1, 4
Renal Dose Adjustment Algorithm
Critical threshold: Dose adjustment is mandatory when creatinine clearance ≤50 mL/min to prevent drug accumulation and neurotoxicity 2
Specific Adjustments by Creatinine Clearance:
- CrCl 26-50 mL/min: Reduce to meropenem 1 gram IV every 12 hours 2
- CrCl 10-25 mL/min: Reduce to meropenem 500 mg IV every 12 hours 2
- CrCl <10 mL/min: Reduce to meropenem 500 mg IV every 24 hours 2
- Hemodialysis patients: Administer 500 mg IV every 24 hours, given after dialysis session 2
- CRRT patients: Higher doses than predicted by creatinine clearance formulas may be required due to significant drug removal; consider 1-2 grams every 8-12 hours with therapeutic drug monitoring 3
Neurotoxicity Prevention
Primary risk factor: Renal impairment causes meropenem accumulation, with trough concentrations >64 mg/L associated with neurotoxicity in 50% of patients 2
- Meropenem has lower seizure risk than imipenem (16% relative pro-convulsive activity compared to penicillin G) but still requires careful dosing in CNS infections 2
- Monitor for confusion, myoclonus, or seizures—these indicate potential drug accumulation requiring immediate dose reduction 2
- Never use standard 2 gram every 8 hour dosing in patients with CrCl <50 mL/min without adjustment 2
CSF Penetration Considerations
- Standard dosing (2 grams every 8 hours) achieves CSF concentrations of 1-6.40 μg/mL, exceeding MIC for susceptible pathogens by 3 hours post-infusion 5
- CSF penetration is approximately 15% of serum concentrations in ventriculitis patients 6
- Renal impairment paradoxically may improve CSF penetration due to higher sustained serum levels, but neurotoxicity risk outweighs this benefit 7
- For organisms with MIC ≥0.25 mg/L, even renally-adjusted doses may not achieve adequate CSF concentrations; consider therapeutic drug monitoring 7
Therapeutic Drug Monitoring
- Target serum trough concentrations of 20-30 mg/L when using continuous infusion strategies 6
- CSF sampling can confirm adequate penetration (target >1 mg/L for susceptible organisms) 5, 6
- In critically ill patients with augmented renal clearance, doses up to 8-10 grams/day may be required, but this is not applicable to renally impaired patients 7
Common Pitfalls to Avoid
- Failure to adjust for renal function: Using standard 2 gram every 8 hour dosing in patients with CrCl <50 mL/min risks seizures and encephalopathy 2
- Inadequate treatment duration: Stopping before 21 days for Enterobacteriaceae meningitis risks treatment failure 1, 4
- Monotherapy for resistant organisms: Meropenem should be combined with another active agent for ESBL or carbapenem-resistant organisms 1, 3
- Ignoring vancomycin trough levels: When co-administered for resistant pneumococcus, maintain vancomycin troughs of 15-20 μg/mL 1, 4