Predictors of insufficient amikacin peak concentration in critically ill patients receiving a 25?mg/kg total body weight regimen

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• 作者：Etienne de Montmollin (1)
  Lila Bouadma (1)
  Nathalie Gault (2) (3) (4)
  Bruno Mourvillier (1)
  Eric Mariotte (1)
  Sarah Chemam (1)
  Laurent Massias (5)
  Emmanuelle Papy (5)
  Florence Tubach (2) (3) (4)
  Michel Wolff (1)
  Romain Sonneville (1)
  
• 关键词：Amikacin ; Aminoglycoside ; Sepsis ; Loading dose ; Intensive care ; Pharmacodynamics
• 刊名：Intensive Care Medicine
• 出版年：2014
• 出版时间：July 2014
• 年：2014
• 卷：40
• 期：7
• 页码：998-1005
• 全文大小：
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• 作者单位：Etienne de Montmollin (1)
  Lila Bouadma (1)
  Nathalie Gault (2) (3) (4)
  Bruno Mourvillier (1)
  Eric Mariotte (1)
  Sarah Chemam (1)
  Laurent Massias (5)
  Emmanuelle Papy (5)
  Florence Tubach (2) (3) (4)
  Michel Wolff (1)
  Romain Sonneville (1)
  
  1. Service de Réanimation Médicale et des Maladies Infectieuse, H?pital Bichat–Claude-Bernard, Assistance Publique–H?pitaux de Paris, Université Paris Diderot, PRES Sorbonne Paris Cité, 46 rue Henri Huchard, 75877 cedex 18, Paris, France
  2. Département d’Epidémiologie et Recherche Clinique, H?pital Bichat–Claude-Bernard, Assistance Publique–H?pitaux de Paris, 46 rue Henri Huchard, 75877 cedex 18, Paris, France
  3. INSERM CIC, 1425-EC, UMR 1123 ECEVE, 75018, Paris, France
  4. Université Paris Diderot, PRES Sorbonne Paris Cité, UMR 1123 ECEVE, 75018, Paris, France
  5. Pharmacie, H?pital Bichat-Claude Bernard, Assistance Publique-H?pitaux de Paris, Université Paris Diderot, PRES Sorbonne Paris Cité, 46 rue Henri Huchard, Paris, 75877 cedex 18, France
  
• ISSN：1432-1238

文摘

Purpose Amikacin requires pharmacodynamic targets of peak serum concentration (C max) of 8-0 times the minimal inhibitory concentration, corresponding to a target C max of 60-0?mg/L for the less susceptible bacteria. Even with new dosing regimens of 25?mg/kg, 30?% of patients do not meet the pharmacodynamic target. We aimed to identify predictive factors for insufficient C max in a population of critically ill patients. Methods Prospective observational monocentric study of patients admitted to a general ICU and requiring a loading dose of amikacin. Amikacin was administered intravenously at the dose of 25?mg/kg of total body weight. Independent determinants of C max?<?60?mg/L were identified by mixed model multivariate analysis. Results Over a 1-year period, 181 episodes in 146 patients (SAPS 2?=?51 [41-8]) were included. At inclusion, the SOFA score was 8 [6-2], 119 (66?%) episodes required vasopressors, 150 (83?%) mechanical ventilation, and 81 (45?%) renal replacement therapy. The amikacin C max was 69 [54.9-4.4] mg/L. Overall, 60 (33?%) episodes had a C max?<?60?mg/L. The risk of C max?<?60?mg/L associated with BMI?<?25?kg/m2 varied across quarters of inclusion. Independent risk factors for C max?<?60?mg/L were a BMI?<?25?kg/m2 over the first quarter (odds ratio (OR) 15.95, 95?% confidence interval (CI) [3.68-9.20], p?<?0.001) and positive 24-h fluid balance (OR per 250-mL increment 1.06, 95?% [CI 1.01-.11], p?=?0.018). Conclusions Despite an amikacin dose of 25?mg/kg of total body weight, 33?% of patients still had an amikacin C max?<?60?mg/L. Positive 24-h fluid balance was identified as a predictive factor of C max?<?60?mg/L. When total body weight is used, low BMI tended to be associated with amikacin underdosing. These results suggest the need for higher doses in patients with a positive 24-h fluid balance in order to reach adequate therapeutic targets.