What is the dosing for piperacillin(tazobactam) in adults with normal renal function and impaired renal function?

Piperacillin/Tazobactam Dosing

For adults with normal renal function, the standard dose is 3.375 g every 6 hours for most infections, or 4.5 g every 6 hours for nosocomial pneumonia, administered as an intravenous infusion over 30 minutes. 1

Standard Dosing in Adults with Normal Renal Function

For infections other than nosocomial pneumonia:

• Dose: 3.375 g (3 g piperacillin/0.375 g tazobactam) every 6 hours 1
• Total daily dose: 13.5 g (12 g piperacillin/1.5 g tazobactam) 1
• Duration: 7-10 days 1

For nosocomial pneumonia:

• Dose: 4.5 g (4 g piperacillin/0.5 g tazobactam) every 6 hours 1
• Total daily dose: 18 g (16 g piperacillin/2 g tazobactam) 1
• Duration: 7-14 days 1
• Must be combined with an aminoglycoside initially; continue aminoglycoside if Pseudomonas aeruginosa is isolated 1

For critically ill patients, higher doses may be required:

• 4.5 g every 6 hours is recommended for critically ill patients with intra-abdominal infections 2
• Some guidelines suggest doses up to 24 g/day in patients with augmented renal clearance 2

Extended Infusion Strategy

Extended infusion (3-4 hours) is strongly preferred over standard 30-minute infusions to optimize pharmacodynamic targets, particularly in critically ill patients or infections with less susceptible organisms. 2, 3

• Extended infusion increases the time above MIC (T>MIC), which is the critical pharmacodynamic parameter for beta-lactams 2
• Meta-analyses demonstrate improved outcomes with extended/continuous infusion in critically ill patients with sepsis 2
• This approach is especially important for organisms with higher MICs (e.g., Pseudomonas aeruginosa) 2

Dosing in Renal Impairment

Dose reduction is mandatory when creatinine clearance falls below 40 mL/min to prevent drug accumulation and neurotoxicity. 1

Specific Renal Dosing Adjustments

For CrCl 20-40 mL/min:

• Non-nosocomial infections: 2.25 g every 6 hours 1
• Nosocomial pneumonia: 3.375 g every 6 hours 1

For CrCl <20 mL/min:

• Non-nosocomial infections: 2.25 g every 8 hours 1
• Nosocomial pneumonia: 2.25 g every 6 hours 1

For hemodialysis patients:

• Non-nosocomial infections: 2.25 g every 12 hours 1
• Nosocomial pneumonia: 2.25 g every 8 hours 1
• Administer an additional 0.75 g after each dialysis session (hemodialysis removes 30-40% of the dose) 1, 4
• Give the dose after dialysis to facilitate directly observed therapy and avoid premature drug removal 5

For CAPD patients:

• Non-nosocomial infections: 2.25 g every 12 hours 1
• Nosocomial pneumonia: 2.25 g every 8 hours 1
• No supplemental dose needed 1

Critical Considerations in Renal Impairment

The dosing frequency should be reduced while maintaining the milligram dose per administration to preserve concentration-dependent bactericidal effects. 5

• Smaller doses may reduce drug efficacy 5
• Patients with residual renal function (CrCl >50 mL/min) may have significantly higher drug clearance even while on CRRT, requiring higher doses 3, 6
• Therapeutic drug monitoring is strongly recommended for patients on CRRT due to significant pharmacokinetic variability 3

Neurotoxicity Risk

Neurotoxicity is a significant concern in renal impairment due to drug accumulation, particularly when piperacillin levels exceed 157 mg/L in combination with tazobactam. 2, 3

• Piperacillin plasma concentrations above 157 mg/L predict neurological disorders with 97% specificity in ICU patients 2
• When the free minimum concentration to MIC ratio (fCmin/MIC) exceeds 8, approximately 50% of ICU patients develop neurological deterioration 2
• Regular monitoring of renal function is essential during therapy, especially in critically ill patients with fluctuating renal status 3
• Consider therapeutic drug monitoring 24-48 hours after starting treatment, after dosage changes, or with significant clinical changes 3

Pediatric Dosing (≥2 months, ≤40 kg)

For children 2-9 months:

• Appendicitis/peritonitis: 90 mg/kg every 8 hours 1
• Nosocomial pneumonia: 90 mg/kg every 6 hours 1

For children >9 months:

• Appendicitis/peritonitis: 112.5 mg/kg every 8 hours 1
• Nosocomial pneumonia: 112.5 mg/kg every 6 hours 1

Pediatric patients >40 kg should receive adult dosing 1

Pediatric dosing in renal impairment has not been established 1