What is the dose of piperacillin-tazobactam (Pip/Taz) for osteomyelitis in a patient with impaired renal function on dialysis?

From the Guidelines

For patients with osteomyelitis who have impaired renal function and are on dialysis, the recommended dose of piperacillin-tazobactam (Pip/Taz) should be adjusted to 2.25 grams (2 g piperacillin/0.25 g tazobactam) administered every 8 hours, with an additional dose after each dialysis session, as the standard dose of 3.375 g every 6 hours may lead to drug accumulation and toxicity due to reduced renal clearance 1. The dosage adjustment is necessary because piperacillin-tazobactam is primarily eliminated by the kidneys, and patients with renal impairment have reduced clearance of the medication.

• Key considerations for dosing in patients with impaired renal function on dialysis include:
  • Administering an additional dose after each dialysis session to maintain adequate drug concentrations
  • Monitoring for adverse effects such as seizures, electrolyte abnormalities, and liver function abnormalities
  • Considering therapeutic drug monitoring to ensure adequate drug concentrations
  • Treatment duration for osteomyelitis is generally 4-6 weeks, though this may vary based on clinical response and surgical interventions The standard dose of piperacillin-tazobactam for complicated intra-abdominal infections is 3.375 g every 6 hours, but this dose may need to be adjusted in patients with renal impairment 1.
• It is essential to note that the medication should be administered intravenously, typically over 30 minutes to avoid vein irritation. Regular assessment of clinical response and monitoring for adverse effects is essential during treatment. In patients on continuous renal replacement therapy (CRRT), a dose of 2.25-3.375 grams every 6-8 hours may be appropriate, but this should be individualized based on the patient's clinical response and renal function 1.

From the FDA Drug Label

For patients on hemodialysis, the maximum daily dose is 6 g/day (2 g every 8 hours). In addition, because hemodialysis removes 30% to 50% of piperacillin in 4 hours, a 1-g additional dose should be administered following each dialysis period. The dose of piperacillin-tazobactam for osteomyelitis in a patient with impaired renal function on dialysis is 6 g/day (2 g every 8 hours), with an additional 1-g dose administered after each dialysis period 2.

• Key points:
  • Maximum daily dose: 6 g/day
  • Dosing interval: every 8 hours
  • Additional dose after dialysis: 1 g

From the Research

Dosing of Piperacillin-Tazobactam for Osteomyelitis in Patients on Dialysis

The dosing of piperacillin-tazobactam (Pip/Taz) for osteomyelitis in patients with impaired renal function on dialysis is crucial for effective treatment.

• The study 3 recommends dosage alterations for creatinine clearance values less than 40 ml/min, as piperacillin and tazobactam total body clearance, area under the curve, and terminal elimination rate correlated with renal function.
• Hemodialysis removed 31% and 39% of piperacillin and tazobactam, respectively, indicating the need for adjusted dosing in patients undergoing dialysis.
• Another study 4 suggests 8-hourly dosing of patients with renal failure on continuous venovenous haemofiltration (CVVH) or continuous venovenous haemodiafiltration (CVVHDF) with dialysis flow rates of 1 or 2 L/h treated with piperacillin 4 g/tazobactam 0.5 g.

Considerations for Patients on Dialysis

• Patients with acute renal failure undergoing CVVH or CVVHDF may require adjusted dosing of piperacillin-tazobactam, as the elimination half-life and clearance of the drugs are affected by the dialysis process 4.
• The use of extended-infusion strategies, such as piperacillin/tazobactam 3.375 or 4.5 g given every 8 hours, may help maintain desired serum levels throughout the dosing interval in patients receiving Molecular Adsorbent Recirculating System (MARS) therapy 5.

Osteomyelitis Treatment

• While the studies 6 and 7 discuss the treatment of osteomyelitis, they do not provide specific dosing recommendations for piperacillin-tazobactam in patients on dialysis.
• The choice of antibiotic and dosing strategy should be individualized based on the patient's renal function, dialysis modality, and other clinical factors.