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Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
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Standard dosing of piperacillin and meropenem fail to achieve adequate plasma concentrations in ICU patients

J Petersson1,2, C G Giske3,4, E Eliasson5,6

  • 1Function Perioperative Medicine and Intensive Care, Karolinska University hospital Solna, Stockholm, Sweden. johan.petersson@karolinska.se.

Acta Anaesthesiologica Scandinavica
|September 23, 2016
PubMed
Abstract

Insights

Plasma concentrations of piperacillin-tazobactam and meropenem vary significantly in intensive care unit (ICU) patients. Standard dosing leads to suboptimal antibiotic levels in a substantial percentage of patients, even with similar renal function.

Area of Science:

  • Pharmacokinetics
  • Infectious Diseases
  • Critical Care Medicine

Background:

  • Optimal dosing of beta-lactam antibiotics in intensive care units (ICUs) remains debated.
  • The necessity of therapeutic drug monitoring for these antibiotics in critically ill patients is unclear.

Purpose of the Study:

  • To evaluate plasma concentrations of piperacillin-tazobactam and meropenem in ICU patients.
  • To compare measured antibiotic concentrations against established breakpoints for Pseudomonas aeruginosa.

Main Methods:

  • Studied ICU patients receiving piperacillin-tazobactam or meropenem, excluding those on renal replacement therapy.
  • Measured antibiotic concentrations at mid and end-dosing intervals, estimating glomerular filtration rate (GFR) using creatinine and cystatin C.
  • Compared concentrations to susceptibility breakpoints of 16 mg/l for piperacillin and 2 mg/l for meropenem.

Main Results:

  • Analyzed 33 and 31 samples from 20 and 19 patients, respectively.
  • Observed significant inter-patient variability in concentrations (e.g., piperacillin: 27.0 mg/l mid, 8.6 mg/l end; meropenem: 7.5 mg/l mid, 2.4 mg/l end).
  • Found 27% and 61% of piperacillin, and 6% and 48% of meropenem concentrations below breakpoints at mid and end-intervals, respectively.

Conclusions:

  • Standard doses of piperacillin-tazobactam and meropenem result in >10-fold variations in plasma concentrations in ICU patients.
  • A significant proportion of patients exhibit suboptimal antibiotic concentrations.
  • High inter-patient variability in drug levels persists even among patients with similar renal function.

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