Renal-Adjusted Dosing for Cefepime-Tazobactam
For cefepime-tazobactam (WCK 4282), administer 2g every 8 hours as a 1.5-hour infusion in patients with normal renal function, reducing to 1g every 8 hours for moderate impairment (CrCl 30-59 mL/min), 500mg every 8 hours for severe impairment (CrCl 15-29 mL/min), and 500mg every 12 hours for very severe impairment (CrCl 8-14 mL/min) or intermittent hemodialysis, with all doses given after dialysis sessions. 1, 2
Dosing Algorithm by Renal Function
Normal to Mildly Impaired Renal Function (CrCl ≥60 mL/min)
- Standard dose: 2g cefepime/2g tazobactam every 8 hours, infused over 1.5 hours 2
- This regimen achieves 99% probability of target attainment for ESBL-producing pathogens with MIC up to 16 mg/L 2
Moderate Renal Impairment (CrCl 30-59 mL/min)
- Reduced dose: 1g cefepime/1g tazobactam every 8 hours, infused over 1.5 hours 2
- Plasma exposure increases 2.3-fold for both cefepime and tazobactam at this level of renal dysfunction 3
Severe Renal Impairment (CrCl 15-29 mL/min)
- Further reduced dose: 500mg cefepime/500mg tazobactam every 8 hours, infused over 1.5 hours 2
- Exposure increases 4.0- to 4.7-fold compared to normal renal function 3
Very Severe Renal Impairment (CrCl 8-14 mL/min)
- Lowest dose: 500mg cefepime/500mg tazobactam every 12 hours, infused over 1.5 hours 1, 2
- Exposure increases 8.5-fold for cefepime and 11.6-fold for tazobactam 3
End-Stage Renal Disease on Intermittent Hemodialysis
- Dialysis dosing: 500mg cefepime/500mg tazobactam every 12 hours, infused over 1.5 hours 1, 2
- Critical timing: Always administer the dose after hemodialysis sessions to prevent premature drug removal 1
- Hemodialysis removes significant drug, necessitating post-dialysis supplementation 3
Augmented Renal Clearance (CrCl 120-180 mL/min)
For critically ill patients with augmented renal clearance:
- Modified regimen: 2g every 8 hours administered as a prolonged 4-hour infusion (rather than 1.5 hours) 2
- Standard dosing with short infusions may result in subtherapeutic concentrations in this population 2
Critical Monitoring Parameters
Neurotoxicity Surveillance
- High-risk threshold: Monitor closely when CrCl <30 mL/min, as cefepime has relative pro-convulsive activity of 160 1
- Toxic concentrations: Trough levels >22 mg/L (intermittent infusions) or steady-state >35 mg/L (continuous infusion) confer 50% risk of neurotoxicity 1
- Clinical manifestations: Watch for confusion, encephalopathy, myoclonus, and seizures—altered mental status occurs in 92% of neurotoxicity cases 1, 4
Therapeutic Drug Monitoring
- Indications: Consider TDM in all patients with CrCl <30 mL/min or fluctuating renal function 1
- Target range: Maintain trough concentrations between 4-8 times the MIC to balance efficacy and toxicity 1
- Timing: Obtain levels 24-48 hours after initiation or with significant changes in clinical condition 1
Renal Function Assessment
- Frequency: Reassess creatinine clearance daily in critically ill patients, as renal function can fluctuate rapidly 1
- Dose adjustment: Modify dosing immediately when renal function category changes 2
Common Pitfalls to Avoid
Timing Errors with Hemodialysis
- Never administer before dialysis: Pre-dialysis dosing leads to premature drug removal and subtherapeutic levels 1
- Approximately 66% of cefepime and 56% of tazobactam are removed during a single hemodialysis session (extrapolated from similar beta-lactam/tazobactam combinations) 5
Dose Reduction Errors
- Do not reduce individual milligram doses below recommended amounts: Smaller doses compromise the concentration-dependent bactericidal effect 1
- The dose frequency should be reduced (e.g., every 12 hours instead of every 8 hours), but maintain the recommended milligram amount per dose 1
Inadequate Infusion Duration
- For augmented renal clearance, failure to extend infusion time to 4 hours results in inadequate time above MIC 2
- Standard 1.5-hour infusions are insufficient in hypermetabolic states 2