What is the recommended dose of cefepime (Cefepime) for a patient with impaired renal function (creatinine clearance of 23 mL/min) being treated for meningitis?

Cefepime Dosing for Meningitis with CrCl 23 mL/min

For a patient with creatinine clearance of 23 mL/min being treated for meningitis, administer cefepime 2 grams IV every 24 hours, NOT 1 gram every 12 hours. This recommendation is based on FDA-approved renal dosing adjustments that prioritize both efficacy for CNS penetration and safety to avoid neurotoxicity.

Rationale for 2g Q24h Dosing

FDA-Approved Renal Adjustment

• The FDA label specifies that for patients with CrCl 11-29 mL/min receiving the standard 2g every 8-12 hour regimen (used for severe infections), the adjusted dose is 2 grams every 24 hours 1
• This maintains the higher individual dose needed for adequate CNS penetration while extending the dosing interval to prevent drug accumulation 1

Why NOT 1g Q12h

The 1 gram every 12 hours option is inappropriate for meningitis because:

• Inadequate CNS penetration: Cefepime penetration into CSF is already limited (4-34% based on AUC) even with higher doses 2
• Lower peak concentrations: The 1g dose produces insufficient peak levels to achieve adequate CSF concentrations against pathogens with MICs at the upper limits of susceptibility 2
• Meningitis requires maximum dosing: CNS infections demand the highest recommended doses to overcome the blood-brain barrier and achieve bactericidal concentrations 3

Why 2g Q24h is Superior

• Maintains therapeutic peaks: The 2g dose achieves peak plasma concentrations of 63.5-73.9 mg/L, which are not affected by renal impairment 4
• Adequate CSF levels: Most patients receiving 2g doses achieve CSF concentrations above the MIC90 of common nosocomial organisms causing meningitis 2
• Prevents accumulation: The 24-hour interval allows for adequate drug elimination in patients with CrCl 11-29 mL/min, with a half-life of approximately 13.5 hours in this renal function range 4

Critical Safety Considerations

Neurotoxicity Risk with Renal Impairment

Monitor closely for cefepime-associated neurotoxicity (CAN), which occurs more frequently in patients with severe renal dysfunction:

• Patients with CrCl <30 mL/min receiving higher doses (≥4g in first 48 hours) have a 16% incidence of neurotoxicity 5
• Trough concentrations >20 mg/L increase neurotoxicity risk fivefold (OR 5.05,95% CI 1.3-19.8) 6
• Neurotoxicity manifests primarily as altered mental status (92% of cases), confusion, and muscle jerks 3, 5

Monitoring Strategy

Implement therapeutic drug monitoring (TDM) if available:

• Target trough concentrations <20 mg/L to minimize neurotoxicity risk 6
• If trough levels reach 20-30 mg/L, consider dose reduction or extended interval even if symptoms are absent 3
• Neurotoxicity symptoms typically resolve promptly after drug discontinuation 3

Treatment Duration

Continue cefepime for pathogen-specific durations:

• 10-14 days for pneumococcal meningitis (14 days if resistant organism or delayed clinical response) 7, 8
• 7 days for meningococcal meningitis 8
• 21 days for Gram-negative bacilli (Enterobacteriaceae) meningitis 7, 8

Common Pitfalls to Avoid

1. Do not use 1g Q12h thinking it provides "more frequent dosing" - this sacrifices peak concentrations needed for CNS penetration without improving safety 2

2. Do not assume standard dosing is safe - even with FDA-recommended adjustments, 10% of patients with renal impairment develop drug accumulation and neurotoxicity 3

3. Do not attribute confusion to "ICU delirium" without considering cefepime - neurotoxicity is often missed because symptoms are non-specific 3, 5

4. Do not continue therapy beyond pathogen-specific durations - prolonged exposure increases neurotoxicity risk without improving outcomes 8, 5