Piperacillin Population Pharmacokinetics in Critically Ill Adults During Sustained Low-Efficiency Dialysis

Ann Pharmacother. 2018 Oct;52(10):965-973. doi: 10.1177/1060028018773771. Epub 2018 May 7.


Background: Sustained low-efficiency dialysis (SLED), is increasingly being used in intensive care units (ICUs) but studies informing drug dosing for such patients is lacking.

Objective: To describe the population pharmacokinetics (PKs) of piperacillin/tazobactam in critically ill adults receiving SLED and to provide dosing recommendations.

Methods: This prospective population PK study was conducted in adult ICU patients prescribed piperacillin/tazobactam while receiving SLED; 321 blood samples were obtained from 34 participants during and between approximately 50 SLED treatments for quantification of piperacillin and tazobactam concentrations in plasma. A population PK model was developed. Monte Carlo simulation was used to determine the probability of target attainment and pathogen-specific fractional target attainment at different doses.

Results: From a 2-compartment linear model with zero-order input, the mean (SD) clearance of piperacillin on SLED and off SLED were 4.81 (8.48) and 1.42 (1.54) L/h, respectively. Tazobactam concentrations were not sufficient for analysis. For the target of 50% fT>MIC (unbound concentrations of drug are above the minimum inhibitory concentration for >50% of the dosing interval), 3-g of piperacillin infused over 0.5 hours every 8 hours was appropriate for susceptible organisms with MIC ≤16 mg/L. For life-threatening infections where the target of 100% fT>MIC is preferred, a 9-g dose administered as a continuous infusion every 24 hours was appropriate for susceptible organisms with MIC ≤32 mg/L.

Conclusions and relevance: In critically ill patients receiving SLED, piperacillin doses need to be guided by the frequency of SLED treatments and susceptibility of the known or suspected pathogen.

Keywords: dialysis; drug dosing; pharmacokinetics; piperacillin; piperacillin-tazobactam; renal replacement therapy.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacokinetics
  • Critical Illness / epidemiology
  • Critical Illness / therapy*
  • Female
  • Humans
  • Intensive Care Units
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Piperacillin / administration & dosage
  • Piperacillin / blood
  • Piperacillin / pharmacokinetics*
  • Piperacillin, Tazobactam Drug Combination / administration & dosage
  • Piperacillin, Tazobactam Drug Combination / blood
  • Piperacillin, Tazobactam Drug Combination / pharmacokinetics
  • Prospective Studies
  • Renal Dialysis* / methods
  • Renal Replacement Therapy / methods
  • Tazobactam / administration & dosage
  • Tazobactam / blood
  • Tazobactam / pharmacokinetics


  • Anti-Bacterial Agents
  • Piperacillin, Tazobactam Drug Combination
  • Tazobactam
  • Piperacillin