title: Predictors of insufficient amikacin peak concentration in critically ill patients receiving a 25 mg/kg total body weight regimen.
abstract: OBJECTIVE
  Amikacin requires pharmacodynamic targets of peak serum concentration (Cmax) of 8-10 times the minimal inhibitory concentration, corresponding to a target Cmax of 60-80 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 Cmax 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 Cmax < 60 mg/L were identified by mixed model multivariate analysis.
  
  
  RESULTS
  Over a 1-year period, 181 episodes in 146 patients (SAPS 2 = 51 [41-68]) were included. At inclusion, the SOFA score was 8 [6-12], 119 (66%) episodes required vasopressors, 150 (83%) mechanical ventilation, and 81 (45%) renal replacement therapy. The amikacin Cmax was 69 [54.9-84.4] mg/L. Overall, 60 (33%) episodes had a Cmax < 60 mg/L. The risk of Cmax < 60 mg/L associated with BMI < 25 kg/m(2) varied across quarters of inclusion. Independent risk factors for Cmax < 60 mg/L were a BMI < 25 kg/m(2) over the first quarter (odds ratio (OR) 15.95, 95% confidence interval (CI) [3.68-69.20], p < 0.001) and positive 24-h fluid balance (OR per 250-mL increment 1.06, 95% [CI 1.01-1.11], p = 0.018).
  
  
  CONCLUSIONS
  Despite an amikacin dose of 25 mg/kg of total body weight, 33% of patients still had an amikacin Cmax < 60 mg/L. Positive 24-h fluid balance was identified as a predictive factor of Cmax < 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.
authors.affiliation: Service de Réanimation Médicale et des Maladies Infectieuse, Hôpital Bichat-Claude-Bernard, Assistance Publique-Hôpitaux de Paris, Université Paris Diderot, PRES Sorbonne Paris Cité, 46 rue Henri Huchard, 75877 cedex 18, Paris, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: de Montmollin
authors.forename: Lila
authors.initials: L
authors.lastname: Bouadma
authors.forename: Nathalie
authors.initials: N
authors.lastname: Gault
authors.forename: Bruno
authors.initials: B
authors.lastname: Mourvillier
authors.forename: Eric
authors.initials: E
authors.lastname: Mariotte
authors.forename: Sarah
authors.initials: S
authors.lastname: Chemam
authors.forename: Laurent
authors.initials: L
authors.lastname: Massias
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Papy
authors.forename: Florence
authors.initials: F
authors.lastname: Tubach
authors.forename: Michel
authors.initials: M
authors.lastname: Wolff
authors.forename: Romain
authors.initials: R
authors.lastname: Sonneville
mesh_terms: D000368:Aged; D000583:Amikacin / Q000008:administration & dosage* / Q000097:blood*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000097:blood*; D015992:Body Mass Index; D001835:Body Weight; D016638:Critical Illness; D004305:Dose-Response Relationship, Drug; D005260:Female; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy; D006801:Humans; D007262:Infusions, Intravenous; D007267:Injections; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D000900:Anti-Bacterial Agents; D000583:Amikacin