Standard dosing of amikacin and gentamicin in critically ill patients results in variable and subtherapeutic concentrations

Int J Antimicrob Agents. 2015 Jul;46(1):21-7. doi: 10.1016/j.ijantimicag.2015.02.009. Epub 2015 Mar 19.

Abstract

Low peak plasma concentrations (Cmax) of amikacin and gentamicin are reported in intensive care unit (ICU) patients after administration of the first dose. The present study aimed to describe the proportion of ICU patients in whom an adequate Cmax was achieved throughout the course of therapy. Septic ICU patients with an indication for intravenous amikacin or gentamicin were eligible for inclusion in this single-centre observational study. The first and subsequent doses and the corresponding Cmax values were recorded. The target Cmax was ≥60mg/L for amikacin and ≥30mg/L for gentamicin. Amikacin and gentamicin plasma concentrations were available in 66 and 24 patients, respectively (59±17 years; 79±19kg; height 169±12cm; SAPS II score 46±19). Pulmonary, abdominal and urinary tract infections were diagnosed in 64 patients. Culture-positive infection was confirmed in 65 patients (72%). A target first Cmax was achieved in 17/90 patients (19%). For amikacin, the target Cmax was achieved in 16/66 patients (24%) after the initial dose. In the 50 remaining patients, a change in dosing was performed in 14 patients, leading adequate peak plasma level in 2 patients. For gentamicin, the targeted Cmax was achieved in only 1/24 patient (4%) after the initial dose and was never achieved after the third dose. In conclusion, standard dosing of amikacin or gentamicin led to adequate Cmax in only 19% of patients. Subtherapeutic Cmax were not significantly corrected after subsequent doses.

Keywords: Aminoglycoside; ICU; Peak plasma concentration.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amikacin / administration & dosage*
  • Amikacin / pharmacokinetics*
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / pharmacokinetics*
  • Bacterial Infections / drug therapy
  • Cohort Studies
  • Critical Illness
  • Female
  • Gentamicins / administration & dosage*
  • Gentamicins / pharmacokinetics*
  • Humans
  • Intraabdominal Infections / drug therapy
  • Male
  • Middle Aged
  • Plasma / chemistry*
  • Pneumonia, Bacterial / drug therapy
  • Urinary Tract Infections / drug therapy

Substances

  • Anti-Bacterial Agents
  • Gentamicins
  • Amikacin