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

From the Guidelines

For patients with osteomyelitis who have impaired renal function and are on hemodialysis, the recommended dose of piperacillin/tazobactam (Pip/Taz) is 2.25 grams (2 g piperacillin/0.25 g tazobactam) administered every 8 hours, with an additional dose after each dialysis session. This dosing regimen accounts for the reduced drug clearance in renal failure while ensuring adequate antimicrobial coverage for bone infections. It's essential to administer the dose after dialysis completion since hemodialysis can remove a significant portion of the medication from the bloodstream. For osteomyelitis treatment, therapy typically continues for 4-6 weeks total, though duration may be adjusted based on clinical response, causative organism, and surgical interventions 1. Blood levels should be monitored periodically if available, especially in prolonged treatment courses. This dosing recommendation balances the need for sufficient antibiotic concentration at the infection site while minimizing toxicity risks in patients with impaired drug elimination. Therapeutic drug monitoring may be beneficial in optimizing treatment in these complex cases. Key considerations include:

• Administering the dose after dialysis completion to avoid significant drug removal by hemodialysis
• Monitoring blood levels periodically, especially in prolonged treatment courses
• Adjusting the duration of therapy based on clinical response, causative organism, and surgical interventions
• Considering therapeutic drug monitoring to optimize treatment in complex cases. Given the provided evidence, the most relevant and recent guideline for managing infections in patients with impaired renal function, including those on hemodialysis, is from 1, which supports the recommended dosing regimen for piperacillin/tazobactam in this context.

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 recommended dose of piperacillin/tazobactam for a patient with impaired renal function on dialysis (hemodialysis) with osteomyelitis is 6 g/day (2 g every 8 hours), with an additional 1-g dose administered after each dialysis period 2.

From the Research

Dosing of Piperacillin/Tazobactam for Osteomyelitis in Patients on Dialysis

• The recommended dose of piperacillin/tazobactam (Pip/Taz) for patients with impaired renal function on dialysis (hemodialysis) with osteomyelitis is not explicitly stated in the provided studies, but several studies provide guidance on dosing in patients with renal impairment.
• A study from 1992 3 found that hemodialysis removed 31% and 39% of piperacillin and tazobactam, respectively, and recommended dosage alterations for creatinine clearance values less than 40 ml/min.
• Another study from 2011 4 demonstrated that dialysate drug levels predicted plasma free drug levels well, suggesting a strategy for therapeutic drug monitoring that minimizes blood loss from phlebotomy and simplifies analytic procedures.
• A study from 2001 5 recommended 8-hourly dosing of patients with renal failure on continuous venovenous hemofiltration (CVVH) or continuous venovenous hemodiafiltration (CVVHDF) with dialysis flow rates of 1 or 2 L/h treated with piperacillin 4 g/tazobactam 0.5 g.
• A study from 2018 6 found that for the target of 50% fT>MIC, 3-g of piperacillin infused over 0.5 hours every 8 hours was appropriate for susceptible organisms with MIC ≤16 mg/L in critically ill patients receiving sustained low-efficiency dialysis (SLED).
• A study from 2017 7 evaluated the pharmacodynamic exposure of piperacillin/tazobactam across the renal function range using 4.5 or 3.375 g dosing regimens and found that prolonged infusions of 4.5 g (3 hours) and 3.375 g (4 hours) every 6 hours resulted in ≥95% probability of target attainment (PTA) at MICs ≤ 16 μg/mL.

Considerations for Dosing

• The dosing of piperacillin/tazobactam in patients on dialysis should be guided by the frequency of dialysis treatments and the susceptibility of the known or suspected pathogen 6.
• Prolonged infusions of piperacillin/tazobactam may provide similar or better probability of target attainment compared to standard regimens 7.
• Therapeutic drug monitoring using dialysate effluent may be a useful strategy to minimize blood loss from phlebotomy and simplify analytic procedures 4.