Dialytic Removal of Meropenem and Piperacillin-Tazobactam
Both meropenem and piperacillin-tazobactam are significantly removed by dialysis, requiring dose adjustments and post-dialysis supplementation to maintain therapeutic concentrations.
Meropenem Removal by Dialysis
Hemodialysis (HD)
- Meropenem is readily dialyzable, with approximately 50% of the drug eliminated during a standard intermittent hemodialysis session 1
- The half-life of meropenem extends dramatically from approximately 1 hour in healthy individuals to up to 13.7 hours in anuric patients with end-stage renal disease 1
- Meropenem and its metabolite are effectively removed by hemodialysis, necessitating dosage adjustments 2
Sustained Low-Efficiency Dialysis (SLED)
- During an 8-hour SLED session, the mean reduction of plasma meropenem concentration is 79.1% 3
- The half-life during SLED is approximately 3.6 hours, with significantly more drug removed in the first 4 hours compared to the remainder of the session 3
- The fraction of drug removal (fD) by SLED ranges from 44-77% across different antimicrobials, with meropenem showing substantial elimination 4
Continuous Renal Replacement Therapy (CRRT)
- Continuous venovenous hemofiltration (CVVHF) removes 25-50% of meropenem 1
- Continuous venovenous hemodiafiltration (CVVHDF) removes 13-53% of meropenem, demonstrating significant variability based on treatment modality 1
Piperacillin-Tazobactam Removal by Dialysis
Hemodialysis (HD)
- An additional dose of 0.75 g should be administered following each dialysis session on hemodialysis days, with post-dialysis administration preferred to avoid premature drug clearance 5
- Therapeutic drug monitoring (TDM) is recommended 24-48 hours after treatment initiation or after any dosage change in patients with impaired renal function 5
Sustained Low-Efficiency Dialysis (SLED)
- The fraction of drug removal (fD) by SLED for piperacillin-tazobactam is substantial, requiring modification of the dosing regimen to avoid subtherapeutic concentrations 4
- An 8-hour SLED session leads to significant elimination, with the half-life on-SLED substantially lower than off-SLED 4
Continuous Renal Replacement Therapy (CRRT)
- During CVVH, the mean 12-hour elimination is 29% for piperacillin and 37% for tazobactam 6
- During CVVHDF at 1 L/h, elimination increases to 42% for piperacillin and 57% for tazobactam 6
- During CVVHDF at 2 L/h, elimination further increases to 46% for piperacillin and 69% for tazobactam 6
- The elimination half-life of piperacillin during CVVH (7.7 hours) is significantly longer than during CVVHDF at 1 L/h (6.7 hours) or 2 L/h (6.1 hours) 6
- Eight-hourly dosing is recommended for patients on CVVH or CVVHDF with dialysis flow rates of 1 or 2 L/h treated with piperacillin 4 g/tazobactam 0.5 g 6
Critical Dosing Considerations
Common Pitfalls to Avoid
- Never administer doses before dialysis sessions, as this leads to premature removal of the drug and subtherapeutic levels 5
- Avoid using standard dosing regimens without appropriate adjustments for the type and intensity of renal replacement therapy 5
- Do not assume all dialysis modalities remove drugs equally—CVVHDF removes significantly more drug than CVVH, and higher flow rates increase clearance 6
Membrane-Specific Factors
- Polysulfone membranes demonstrate significantly higher permeability than AN69 membranes during CVVH, affecting drug clearance rates 7
- Drug binding to albumin contributes to decreased sieving coefficients, though this does not fully explain in vivo clearance values 7
Monitoring Recommendations
- Therapeutic drug monitoring should be performed in patients with expected pharmacokinetic variability, particularly those in the ICU 8
- Patients undergoing renal replacement therapy require particularly careful monitoring of both drug levels and electrolytes 8
- Measure plasma trough concentration for intermittent administration and plasma steady-state concentration for continuous administration 5