Piperacillin-Tazobactam Dosing Based on eGFR
For adults with normal renal function (eGFR >40 mL/min), administer 3.375 g every 6 hours for most infections or 4.5 g every 6 hours for nosocomial pneumonia; when eGFR is 20-40 mL/min, reduce to 2.25 g every 6 hours (or 3.375 g every 6 hours for nosocomial pneumonia); and when eGFR is <20 mL/min, further reduce to 2.25 g every 8 hours (or 2.25 g every 6 hours for nosocomial pneumonia). 1
Standard Dosing Algorithm by Renal Function
The FDA-approved dosing regimen is structured as follows 1:
For All Indications Except Nosocomial Pneumonia:
- eGFR >40 mL/min: 3.375 g every 6 hours (total 13.5 g/day) 1
- eGFR 20-40 mL/min: 2.25 g every 6 hours (total 9 g/day) 1
- eGFR <20 mL/min: 2.25 g every 8 hours (total 6.75 g/day) 1
For Nosocomial Pneumonia:
- eGFR >40 mL/min: 4.5 g every 6 hours (total 18 g/day) 1
- eGFR 20-40 mL/min: 3.375 g every 6 hours (total 13.5 g/day) 1
- eGFR <20 mL/min: 2.25 g every 6 hours (total 9 g/day) 1
All doses should be administered as 30-minute intravenous infusions 1.
Special Considerations for Dialysis Patients
Hemodialysis:
- All indications except nosocomial pneumonia: 2.25 g every 12 hours 1
- Nosocomial pneumonia: 2.25 g every 8 hours 1
- Post-dialysis supplementation: Administer an additional 0.75 g (0.67 g piperacillin/0.08 g tazobactam) after each hemodialysis session, as dialysis removes 30-40% of the administered dose 1
CAPD (Continuous Ambulatory Peritoneal Dialysis):
- Same dosing as hemodialysis but no additional post-dialysis dose required 1
Critical Illness and Pharmacokinetic Optimization
In critically ill patients with sepsis or septic shock, standard dosing may be inadequate due to altered pharmacokinetics 2:
- Extended or continuous infusion of beta-lactams increases the time above MIC (T>MIC) and may improve outcomes, particularly for resistant organisms 2
- A loading dose should be administered as a bolus or rapid infusion to rapidly achieve therapeutic levels, followed by extended infusion over several hours 2
- For severe infections targeting 100% T>MIC, consider increasing dose frequency (e.g., 3.375 g every 6 hours instead of 4.5 g every 8 hours for the same total daily dose) 2
Important Caveats and Pitfalls
Risk of Nephrotoxicity in Renal Impairment:
- Higher doses (4.5 g) are associated with increased acute kidney injury (AKI) risk even when dose frequency is reduced in patients with baseline renal impairment 3
- In patients with eGFR 10-40 mL/min receiving 4.5 g doses, AKI occurred in 25-38.5% of cases, compared to only 5.6% with 2.25 g doses 3
- Monitor renal function closely when using higher doses in patients with any degree of renal impairment 3
Therapeutic Drug Monitoring:
- TDM is recommended in critically ill patients with expected pharmacokinetic variability, particularly those on renal replacement therapy 2
- For intermittent dosing, measure trough concentrations; for continuous infusion, measure steady-state concentrations 2
- Perform TDM 24-48 hours after treatment initiation and after any dosage changes 2
Inadequacy of Standard Dosing for Resistant Organisms:
- Standard dosing achieves adequate exposure for pathogens with MIC ≤8 mg/L in >90% of critically ill patients 4
- For Pseudomonas aeruginosa with MIC of 16 mg/L, there is a narrow therapeutic window between efficacy and toxicity even with doses up to 20 g/24 h 4
- Consider continuous infusion (12-20 g/24 h) for difficult-to-treat infections with higher MICs, guided by TDM to avoid toxicity 5, 4