Experience with a once-daily dosing program of aminoglycosides in critically ill patients

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Updated: Sep 30, 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

S E Buijk1, J W Mouton, I C Gyssens

  • 1Dept. of Surgical Intensive Care, Erasmus MC Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. gyssens@bacl.azr.nl

Intensive Care Medicine
|July 18, 2002
PubMed
Abstract

Insights

Once-daily aminoglycoside (ODA) regimens in critically ill patients showed variable pharmacokinetics, especially in septic shock. Individual therapeutic drug monitoring is essential for optimizing ODA therapy and minimizing nephrotoxicity in this population.

Area of Science:

  • Pharmacology
  • Critical Care Medicine
  • Infectious Diseases

Background:

  • Aminoglycosides exhibit concentration-dependent killing, leading to the adoption of once-daily aminoglycoside (ODA) regimens.
  • Limited data exist on the efficacy and safety of ODA regimens in critically ill patient populations.

Purpose of the Study:

  • To evaluate the effectiveness of the ODA program in critically ill patients.
  • To characterize the pharmacokinetics of gentamicin and tobramycin in this demographic.
  • To assess the incidence of nephrotoxicity associated with ODA therapy.

Main Methods:

  • A prospective, descriptive study was conducted in a surgical and medical intensive care unit.
  • Eighty-nine critically ill patients receiving gentamicin or tobramycin for suspected infections were monitored.
  • Pharmacokinetic profiles were generated from serum samples collected at 1 and 6 hours post-infusion.

Main Results:

  • The volume of distribution for aminoglycosides was significantly higher in patients with septic shock.
  • Maximum concentration (Cmax) was lower in patients with septic shock, impacting Cmax/MIC ratios.
  • Dose adjustments were necessary in 49% of patients treated for over 24 hours; standard nomograms were accurate in only 62% of cases.
  • Nephrotoxicity occurred in 14% of patients, but was reversible in survivors.

Conclusions:

  • The ODA regimen at 7 mg/kg achieved Cmax/MIC ratios greater than 10 in most critically ill patients.
  • Septic shock and renal dysfunction significantly altered aminoglycoside pharmacokinetics, necessitating individual therapeutic drug monitoring.
  • While signs of renal impairment were common with shock, they were reversible, suggesting careful monitoring can mitigate risks.

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