Cefepime Dosing in Moderate Renal Impairment (GFR 58 mL/min)
For a patient with GFR 58 mL/min (creatinine clearance 30-60 mL/min range), administer cefepime 2 grams every 24 hours for severe infections or 1 gram every 24 hours for moderate infections, based on FDA-approved dosing adjustments for renal impairment. 1
Dose Selection Based on Infection Severity
The FDA label provides clear guidance for patients with creatinine clearance 30-60 mL/min 1:
- For severe infections (pneumonia due to Pseudomonas aeruginosa, febrile neutropenia, complicated intra-abdominal infections): 2 grams every 12 hours 1
- For moderate infections (uncomplicated pneumonia, complicated UTI, skin infections): 1 gram every 24 hours 1
- For mild infections (uncomplicated UTI): 500 mg every 24 hours 1
Your patient's GFR of 58 mL/min places them in the 30-60 mL/min category, requiring dose adjustment from standard dosing 1.
Rationale for Dose Adjustment
The key principle is extending dosing intervals rather than reducing individual doses to maintain adequate peak concentrations for bactericidal activity while preventing drug accumulation 1. Cefepime is primarily renally cleared, and patients with creatinine clearance ≤60 mL/min eliminate the drug more slowly, requiring compensation through interval extension 1.
Research demonstrates that with a creatinine clearance of 60 mL/min, cefepime dosed at 2 grams every 24 hours maintains time above MIC (T>MIC) for ≥75-92% of the dosing interval against Pseudomonas aeruginosa with MICs up to 8 mcg/mL 2. This pharmacodynamic target is critical for beta-lactam efficacy.
Critical Safety Considerations
Monitor closely for neurotoxicity, particularly altered mental status, as this is the most common manifestation of cefepime-associated neurotoxicity (occurring in 92% of affected patients) 3. While neurotoxicity occurs infrequently overall (4-10% in critically ill patients), the risk increases substantially in patients with severe renal dysfunction receiving higher cumulative doses 3, 4.
Patients with GFR <20 mL/min have mean GFR values of 17.20 mL/min when developing encephalopathy versus 32.59 mL/min in those without encephalopathy (p=0.025) 4. Your patient with GFR 58 mL/min has lower risk, but vigilance remains important.
Administration Details
- Infusion time: Administer intravenously over approximately 30 minutes 1
- Timing: Administer at the same time each day to maintain consistent drug levels 1
- Duration: Continue for infection-specific durations (7-10 days for most infections) 1
Common Pitfalls to Avoid
Do not simply reduce the dose without extending the interval, as this results in subtherapeutic peak concentrations and treatment failure 5. The strategy must be interval extension to prevent accumulation while maintaining bactericidal peaks 5.
Do not use serum creatinine alone for dosing decisions—always calculate creatinine clearance using the Cockcroft-Gault equation, as serum creatinine can be misleading, particularly in elderly patients with low muscle mass 1, 6. For your patient: CrCl = [Weight(kg) × (140 - age)] / [72 × 1.4] for males, or 0.85 × this value for females 1.
Avoid concurrent nephrotoxins (NSAIDs, aminoglycosides without careful monitoring) as these compound toxicity risk in patients already receiving renally-cleared medications 6.
Monitoring Parameters
- Renal function: Reassess creatinine and calculate CrCl every 2-3 days during therapy, especially if clinical status changes 6
- Mental status: Daily assessment for confusion, altered consciousness, myoclonus, or seizures 3, 4
- Clinical response: Fever curve, white blood cell count, source control for infection 1
If neurotoxicity develops, discontinue cefepime immediately—symptoms typically resolve within 48 hours of drug discontinuation 3, 4.