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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
Summary
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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