Suboptimal aminoglycoside dosing in critically ill patients

Rhonda S. Rea, Blair Capitano, Robert Bies, Kristin L. Bigos, Randall Smith, Howard Lee

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

Maximal aminoglycoside (AG) killing requires that the ratio of peak serum concentrations (Cmax) to the minimum inhibitory concentration (MIC) of the pathogen exceeds by ≥10. This has been shown to hasten resolution of infection in the general patient population. It was postulated that critically ill patients, likely to have larger intravascular volumes, are underdosed. The primary aim was to determine Cmax to MIC target attainment rate in medical intensive care unit (MICU) patients. A retrospective review of MICU patients who received at least 1 intravenous dose and serum concentration of either gentamicin or tobramycin was performed. A population pharmacokinetic model was developed, and MIC distributions for AG were used in determining the Cmax/MIC and in calculating the probability of attaining the pharmacodynamic (PD) target. One hundred two unique patients with 211 AG concentrations were analyzed to determine population pharmacokinetic parameters. Mean maximum clearance (CL) was 3.14L/h (95% confidence interval: 1.26-4.54 L/h), and mean volume of distribution (V) was 53 L (95% confidence interval: 38-66.8 L/h). Glomerular filtration rate and standardized body weight were identified as significant covariates for clearance in the final model. Standardized body weight also significantly affected V. There was only a 20% and 40% probability that patients receiving 7 mg/kg of gentamicin and tobramycin, respectively, will achieve PD target over the range of MIC distributions. Based on these data, the majority of critically ill patients would not be predicted to achieve the PD target under current dosing regimens. This may be a result of intensive care unit patients having a larger volume of distribution than reported in the literature. Future recommendations for treating gram-negative infections in the MICU population include using initial doses of 7 mg/kg of either gentamicin or tobramycin, measuring Cmax after the first dose, and determining MIC for the pathogen(s) with adjustment of subsequent doses to achieve the PD target.

Original languageEnglish (US)
Pages (from-to)674-681
Number of pages8
JournalTherapeutic Drug Monitoring
Volume30
Issue number6
DOIs
StatePublished - Dec 2008
Externally publishedYes

Fingerprint

Aminoglycosides
Critical Illness
Microbial Sensitivity Tests
Tobramycin
Intensive Care Units
Gentamicins
Population
Pharmacokinetics
Body Weight
Confidence Intervals
Infection
Serum
Glomerular Filtration Rate

Keywords

  • Aminoglycosides
  • Intensive care unit
  • Pharmacodynamics
  • Pharmacokinetics

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

Cite this

Suboptimal aminoglycoside dosing in critically ill patients. / Rea, Rhonda S.; Capitano, Blair; Bies, Robert; Bigos, Kristin L.; Smith, Randall; Lee, Howard.

In: Therapeutic Drug Monitoring, Vol. 30, No. 6, 12.2008, p. 674-681.

Research output: Contribution to journalArticle

Rea, Rhonda S. ; Capitano, Blair ; Bies, Robert ; Bigos, Kristin L. ; Smith, Randall ; Lee, Howard. / Suboptimal aminoglycoside dosing in critically ill patients. In: Therapeutic Drug Monitoring. 2008 ; Vol. 30, No. 6. pp. 674-681.
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