Cefepime-Tazobactam Dosing in Renal Impairment
For patients with impaired renal function receiving cefepime-tazobactam, reduce the dose to 1g every 8 hours for creatinine clearance 30-59 mL/min, 500mg every 8 hours for CrCl 15-29 mL/min, and 500mg every 12 hours for CrCl 8-14 mL/min or patients on intermittent hemodialysis, with all doses administered as 1.5-hour infusions. 1
Renal Function-Based Dosing Algorithm
Moderate Renal Impairment (CrCl 30-59 mL/min)
- Administer cefepime-tazobactam 1g every 8 hours as a 1.5-hour infusion to maintain adequate exposure against ESBL-producing pathogens with MICs up to 16 mg/L 1
- This dosing achieves a combined probability of target attainment (PTA) of 99% for the therapeutic target required for bacterial killing 1
Severe Renal Impairment (CrCl 15-29 mL/min)
- Reduce dose to 500mg every 8 hours as a 1.5-hour infusion 1
- This adjustment prevents drug accumulation while maintaining efficacy against piperacillin/tazobactam-resistant ESBL infections 1
Very Severe Renal Impairment (CrCl 8-14 mL/min) and Intermittent Hemodialysis
- Administer 500mg every 12 hours as a 1.5-hour infusion 1
- For hemodialysis patients, give the dose after dialysis sessions to prevent premature drug removal and facilitate directly observed therapy 2
- Approximately 68% of cefepime is removed during a 3-hour dialysis period, necessitating post-dialysis administration 3
Critical Monitoring Considerations
Neurotoxicity Risk in Renal Impairment
- Monitor closely for neurological symptoms including confusion, encephalopathy, myoclonus, and seizures, particularly in patients with CrCl <30 mL/min 2, 4, 5
- Cefepime has a relative pro-convulsive activity of 160 (compared to penicillin G = 100), making it particularly neurotoxic in renal dysfunction 2
- Neurotoxicity can occur even with appropriate dose adjustments, with 10% of ICU patients with renal impairment developing symptoms despite dosage reduction 5
- Trough concentrations above 22 mg/L (intermittent infusions) or steady-state concentrations above 35 mg/L (continuous infusion) are associated with 50% risk of neurotoxicity 2
Therapeutic Drug Monitoring
- Consider therapeutic drug monitoring in all patients with fluctuating renal function or CrCl <30 mL/min to optimize dosing and prevent both treatment failure and toxicity 6, 7, 5
- Target trough concentrations should remain between 4-8 times the MIC, as exceeding 8× MIC increases neurotoxicity risk without additional efficacy benefit 2, 6
Common Pitfalls to Avoid
Dosing Errors in Renal Impairment
- Never administer cefepime-tazobactam before hemodialysis sessions, as this leads to premature drug removal and subtherapeutic levels 8
- Avoid reducing individual doses below the recommended milligram amounts, as smaller doses may compromise the concentration-dependent bactericidal effect even in renal impairment 2, 8
- Do not use standard dosing intervals (every 8 hours with full 2g doses) in patients with CrCl <60 mL/min, as this leads to dangerous drug accumulation 3, 5
Hidden Neurotoxicity
- Maintain high clinical suspicion for non-convulsive encephalopathy, as symptoms may be subtle (confusion, muscle jerks) and easily attributed to other ICU complications 5
- Cefepime-induced encephalopathy can occur even with appropriate dose adjustments, requiring prompt discontinuation when suspected 4, 5
- The half-life of cefepime increases from 2 hours in normal renal function to 13.5 hours in acute or chronic renal impairment, dramatically increasing accumulation risk 4
Special Populations
Continuous Renal Replacement Therapy (CRRT)
- While specific data for cefepime-tazobactam on CRRT are limited, related cephalosporin/beta-lactamase inhibitor combinations suggest maintaining full doses with extended intervals 9, 10
- CRRT removes 25-50% of cephalosporins, necessitating higher doses than standard renal impairment adjustments 8
- Consider therapeutic drug monitoring mandatory in CRRT patients to ensure adequate exposure 8