What is the appropriate intravenous dosing of piperacillin‑tazobactam (Tazocin) based on the patient's estimated glomerular filtration rate (eGFR)?

Piperacillin-Tazobactam (Tazocin) Dosing Based on eGFR

For patients with normal renal function (eGFR >40 mL/min), administer piperacillin-tazobactam 4.5 g every 6 hours as an extended infusion over 3-4 hours; for moderate renal impairment (eGFR 20-40 mL/min), reduce to 3.375 g every 6 hours; and for severe impairment (eGFR <20 mL/min), give 2.25 g every 8 hours. 1

Standard Dosing by Renal Function

eGFR >40 mL/min (Normal to Mild Impairment)

• Non-nosocomial infections: 3.375 g every 6 hours by IV infusion over 30 minutes 1
• Nosocomial pneumonia: 4.5 g every 6 hours (plus aminoglycoside if Pseudomonas aeruginosa suspected) 1
• Optimized regimen: Extended infusion over 3-4 hours significantly improves pharmacodynamic target attainment compared to standard 30-minute infusions, particularly for resistant organisms 2, 3

eGFR 20-40 mL/min (Moderate Impairment)

• Non-nosocomial infections: 2.25 g every 6 hours 1
• Nosocomial pneumonia: 3.375 g every 6 hours 1
• Extended infusions (3-4 hours) achieve ≥98% probability of target attainment at this renal function level 4

eGFR <20 mL/min (Severe Impairment)

• Non-nosocomial infections: 2.25 g every 8 hours 1
• Nosocomial pneumonia: 2.25 g every 6 hours 1
• Prolonged infusions maintain ≥93% probability of target attainment even at this reduced dosing frequency 4

Hemodialysis Patients

• All indications except nosocomial pneumonia: 2.25 g every 12 hours 1
• Nosocomial pneumonia: 2.25 g every 8 hours 1
• Supplemental dose: Administer 0.75 g (0.67 g piperacillin + 0.08 g tazobactam) immediately after each hemodialysis session, as dialysis removes 30-40% of the drug 1
• During high-volume hemodiafiltration in septic shock, 4 g every 8 hours as a 4-hour infusion achieves bactericidal targets 5

CAPD (Continuous Ambulatory Peritoneal Dialysis)

• All indications except nosocomial pneumonia: 2.25 g every 12 hours 1
• Nosocomial pneumonia: 2.25 g every 8 hours 1
• No supplemental dosing required 1

Critical Considerations for Dosing Optimization

Loading Dose Strategy

• Always administer a loading dose as a rapid bolus or short infusion to achieve therapeutic concentrations quickly, regardless of renal function 2, 3
• The loading dose is not affected by renal impairment—use the full standard dose initially, then adjust maintenance dosing based on eGFR 2

Extended vs. Standard Infusion

• Extended infusion (3-4 hours) is superior to standard 30-minute infusion for achieving 100% time above MIC, especially in severe infections and for organisms with MIC ≥8 mg/L 2, 3
• For patients with eGFR ≥100 mL/min (augmented renal clearance), standard dosing often fails to achieve targets; consider increasing to 18-22.5 g/day by continuous infusion 6
• Continuous infusion may be more effective than intermittent dosing in critically ill patients, particularly for relatively resistant organisms 2

Augmented Renal Clearance (eGFR ≥130 mL/min)

• Standard dosing regimens frequently result in subtherapeutic concentrations in patients with augmented renal clearance 7, 6
• The piperacillin:tazobactam ratio increases from 6:1 to 10:1 as eGFR rises from <20 to >120 mL/min, potentially compromising tazobactam coverage 6
• For eGFR 100-120 mL/min: Consider 18 g/day by continuous infusion 6
• For eGFR >120-160 mL/min: Consider 22.5 g/day by continuous infusion 6

Renal Function Assessment

• Calculate creatinine clearance using the U × V/P formula (24-hour urine collection) at treatment initiation and whenever clinical condition or renal function changes significantly 2
• Serum creatinine alone is unreliable in critically ill patients due to altered muscle mass and volume of distribution 2
• Reassess renal function every time therapeutic drug monitoring is performed to interpret results accurately 2

Therapeutic Drug Monitoring (TDM)

When to Monitor

• TDM is strongly recommended for critically ill patients with expected pharmacokinetic variability, especially those on renal replacement therapy 3
• Obtain samples 24-48 hours after therapy initiation and after any dosage changes 3

Target Concentrations

• For intermittent dosing: Measure trough concentrations; target ≥16 mg/L for organisms with MIC ≤16 mg/L 3
• For continuous infusion: Measure steady-state concentrations 3
• Aim for 50% free time above MIC for mild-moderate infections; 100% free time above MIC for severe infections including sepsis 2

Common Pitfalls to Avoid

• Do not assume normal dosing is safe based on "normal" serum creatinine alone—calculate actual creatinine clearance, especially in elderly or critically ill patients with reduced muscle mass 2
• Do not give supplemental hemodialysis doses before dialysis—always administer post-dialysis to prevent premature drug removal 1
• Do not continue standard 30-minute infusions in severe infections—extended infusions (3-4 hours) significantly improve outcomes 2, 3
• Do not overlook augmented renal clearance in younger, critically ill patients with sepsis—these patients often require higher doses despite "normal" eGFR 6
• Loading doses are required even in renal impairment—only maintenance doses need adjustment 2

Pediatric Dosing (≥2 Months, ≤40 kg)

Normal Renal Function

• Ages 2-9 months: 90 mg/kg (80 mg piperacillin + 10 mg tazobactam) every 8 hours for appendicitis/peritonitis; every 6 hours for nosocomial pneumonia 1
• Ages >9 months: 112.5 mg/kg (100 mg piperacillin + 12.5 mg tazobactam) every 8 hours for appendicitis/peritonitis; every 6 hours for nosocomial pneumonia 1
• Pediatric patients >40 kg: Use adult dosing 1
• Dosing in pediatric patients with renal impairment has not been established 1

Duration of Therapy

• Standard infections: 7-10 days 1
• Nosocomial pneumonia: 7-14 days 1