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Updated: Jun 27, 2026

Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
11:17

Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses

Published on: August 30, 2018

Suboptimal aminoglycoside dosing in critically ill patients

Rhonda S Rea1, Blair Capitano, Robert Bies

  • 1Department of Pharmacy and Therapeutics, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Therapeutic Drug Monitoring
|December 6, 2008
PubMed

Insights

Critically ill patients often receive inadequate aminoglycoside (AG) dosing. Current regimens achieve the target peak concentration to minimum inhibitory concentration (MIC) ratio in only 20-40% of medical intensive care unit (MICU) patients.

Area of Science:

  • Pharmacology
  • Critical Care Medicine
  • Infectious Diseases

Background:

  • Maximal aminoglycoside (AG) killing requires a peak serum concentration to minimum inhibitory concentration (Cmax/MIC) ratio of ≥10.
  • This ratio is associated with faster infection resolution in the general population.
  • Critically ill patients may be underdosed due to altered pharmacokinetics, such as increased volume of distribution.

Purpose of the Study:

  • To determine the Cmax/MIC target attainment rate in medical intensive care unit (MICU) patients receiving gentamicin or tobramycin.
  • To evaluate the adequacy of current AG dosing regimens in this population.

Main Methods:

  • Retrospective review of MICU patients who received intravenous gentamicin or tobramycin.
  • Development of a population pharmacokinetic model.
  • Analysis of 211 AG serum concentrations from 102 patients.
  • Calculation of Cmax/MIC and probability of attaining the pharmacodynamic (PD) target using MIC distributions.

Main Results:

  • Mean AG clearance (CL) was 3.14 L/h and volume of distribution (V) was 53 L.
  • Glomerular filtration rate and standardized body weight were significant covariates for CL and V.
  • Only 20% and 40% of patients achieved the PD target with standard gentamicin and tobramycin doses, respectively.

Conclusions:

  • The majority of critically ill patients are predicted to not achieve the AG pharmacodynamic target under current dosing.
  • Larger volume of distribution in ICU patients may contribute to underdosing.
  • Recommendations include higher initial doses (7 mg/kg), Cmax monitoring, and MIC-guided dose adjustments for AG therapy in MICU patients.

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