Target attainment with continuous dosing of piperacillin/tazobactam in critical illness: A prospective observational study

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Abstract

Optimal dosing of β-lactam antibiotics in critically ill patients is a challenge given the unpredictable pharmacokinetic profile of this patient population. Several studies have shown intermittent dosing to often yield inadequate drug concentrations. Continuous dosing is an attractive alternative from a pharmacodynamic point of view. This study evaluated whether, during continuous dosing, piperacillin concentrations reached and maintained a pre-defined target in critically ill patients. Adult patients treated with piperacillin by continuous dosing in the intensive care unit of a university medical centre in The Netherlands were prospectively studied. Total and unbound piperacillin concentrations drawn at fixed time points throughout the entire treatment course were determined by liquid chromatography-tandem mass spectrometry. A pharmacokinetic combined target of a piperacillin concentration ≥80 mg/L, reached within 1 h of starting study treatment AND maintained throughout the treatment course, was set. Eighteen patients were analysed. The median duration of monitored piperacillin treatment was 60 h (interquartile range, 33-96 h). Of the 18 patients, 5 (27.8 %) reached the combined target; 15 (83.3%) reached and maintained a less strict target of >16 mg/L. In this patient cohort, this dosing schedule was insufficient to reach the pre-defined target. Depending on which target is to be met, a larger initial cumulative dose is desirable, combined with therapeutic drug monitoring.

Original languageEnglish
Pages (from-to)68-73
Number of pages6
JournalInternational journal of antimicrobial agents
Volume50
Issue number1
Early online date10-May-2017
DOIs
Publication statusPublished - Jul-2017

Keywords

  • EFFICACY
  • PHARMACODYNAMICS
  • INTENSIVE-CARE-UNIT
  • CONTINUOUS VENOVENOUS HEMOFILTRATION
  • ILL PATIENTS
  • CONTINUOUS-INFUSION
  • SEVERE SEPSIS
  • SEPTIC SHOCK
  • PHARMACOKINETICS
  • TAZOBACTAM
  • beta-Lactam
  • Critical care
  • Continuous dosing
  • Piperacillin

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