Subtherapeutic piperacillin concentrations in neurocritical patients

J Crit Care. 2019 Dec:54:48-51. doi: 10.1016/j.jcrc.2019.07.007. Epub 2019 Jul 10.

Abstract

Purpose: Increased renal elimination is the leading cause for subtherapeutic concentrations of renally cleared antibiotics and it has been hypothesized that brain damaged patients in the intensive care unit (ICU) are particularly at risk. The objective of this study is to determine the prevalence of subtherapeutic piperacillin concentrations in neurocritical patients and to investigate if having a neurocritical diagnosis is a risk factor for this.

Materials and methods: Single center retrospective analysis of a prospective cohort study of adult ICU patients receiving continuous infusion piperacillin/tazobactam. Patients were categorized as either having a neurocritical diagnosis or not. An unbound piperacillin concentration > 4× the epidemiologic cut-off value (ECOFF) of Pseudomonas aeruginosa was selected as the PKPD target of choice. Multivariable logistic regression was performed to identify risk factors for subtherapeutic piperacillin concentrations.

Results: 356 patients had a measured creatinine clearance (mCrCl) and matched piperacillin concentration, 52 of which had a neurocritical diagnosis. Subtherapeutic piperacillin concentrations were reported significantly more frequent in neurocritical patients. In multivariate analysis, the only risk factor identified for subtherapeutic piperacillin concentration was an increasing mCrCl.

Conclusion: Subtherapeutic piperacillin concentrations are common in neurocritical patients yet having a neurocritical admission diagnosis was not identified as an independent risk factor.

Keywords: Beta-lactam antibiotics; Critically ill; Neurocritical care; Piperacillin/tazobactam; Subtherapeutic antibiotic concentrations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anti-Bacterial Agents / pharmacokinetics*
  • Anti-Bacterial Agents / therapeutic use
  • Critical Care / organization & administration*
  • Critical Illness
  • Female
  • Humans
  • Intensive Care Units
  • Kidney / drug effects*
  • Kidney Function Tests
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Piperacillin / pharmacokinetics*
  • Piperacillin / therapeutic use
  • Piperacillin, Tazobactam Drug Combination / therapeutic use*
  • Prospective Studies
  • Pseudomonas aeruginosa
  • Retrospective Studies
  • Risk Factors

Substances

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