title: Assessment of the National French recommendations regarding the dosing regimen of 8mg/kg of gentamicin in patients hospitalised in intensive care units.
abstract: BACKGROUND
  To assess the French National Agency for Medicines and Health Products Safety (ANSM) guidelines concerning the peak plasma concentration (Cmax) of gentamicin when using a loading dose of 8mg/kg administered in patients hospitalised in the intensive care unit (ICU).
  
  
  METHODS
  A prospective observational cohort study conducted in one ICU.
  
  
  RESULTS
  During the study period, 34 patients with a median simplified acute physiology score 2 of 54 [44-70] received a median dose of 8 [7.9-8.1] mg/kg of gentamicin. The median Cmax was 17.5 [15.4-20.7] mg/L and no patient had a Cmax>30mg/L. Twenty-four of 34 patients (71%) had a Cmax>16mg/L. Following multivariate analysis, the only factor associated with Cmax<16mg/L was a positive fluid balance 24hours before gentamicin administration (per 1000mL increment) (OR: 0.37, 95% CI: 0.18-0.77, P=0.008).
  
  
  CONCLUSIONS
  These results suggest that a Cmax>30mg/L [which corresponds to approximately 8 times the minimal inhibiting concentrations (MIC) breakpoints for Pseudomonas aeruginosa and Enterobacteriaceae with intermediate sensitivity] of gentamicin as recommended by ANSM guidelines seems impossible to obtain with a loading dose of 8mg/kg in the ICU. A loading dose of 8mg/kg should probably not be used in the empiric antibiotic treatment of infection due to non-fermenting Gram-negative bacilli and Enterobacteriaceae with intermediate sensitivity whose MIC breakpoint is 4mg/L. A Cmax>16mg/L was not reached in almost 30% of patients, particularly in the group with a positive fluid balance who require higher doses than currently recommended.
authors.affiliation: Réanimation polyvalente, CHU Felix-Guyon, allée des Topazes, 97405 Saint-Denis, France. Electronic address: nicolas.allou@hotmail.fr.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Allou
authors.affiliation: Réanimation polyvalente, CHU Felix-Guyon, allée des Topazes, 97405 Saint-Denis, France. Electronic address: allyn.jer@gmail.com.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Allyn
authors.affiliation: Réanimation polyvalente, CHU Felix-Guyon, allée des Topazes, 97405 Saint-Denis, France. Electronic address: l.yael@hotmail.fr.
authors.forename: Yaël
authors.initials: Y
authors.lastname: Levy
authors.affiliation: Département d'Anesthésie-Réanimation, AP-HP, CHU Bichat-Claude-Bernard, 46, rue Henri-Huchard, 75018 Paris, France. Electronic address: astridbouteau@gmail.com.
authors.forename: Astrid
authors.initials: A
authors.lastname: Bouteau
authors.affiliation: Réanimation polyvalente, CHU Felix-Guyon, allée des Topazes, 97405 Saint-Denis, France. Electronic address: caujollemarie@hotmail.com.
authors.forename: Marie
authors.initials: M
authors.lastname: Caujolle
authors.affiliation: Réanimation polyvalente, CHU Felix-Guyon, allée des Topazes, 97405 Saint-Denis, France. Electronic address: benjamindelmas.desar@yahoo.fr.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Delmas
authors.affiliation: Réanimation polyvalente, CHU Felix-Guyon, allée des Topazes, 97405 Saint-Denis, France. Electronic address: dorothee.valance@gmail.com.
authors.forename: Dorothée
authors.initials: D
authors.lastname: Valance
authors.affiliation: Réanimation polyvalente, CHU Felix-Guyon, allée des Topazes, 97405 Saint-Denis, France. Electronic address: carolinebrulliard@gmail.com.
authors.forename: Caroline
authors.initials: C
authors.lastname: Brulliard
authors.affiliation: Réanimation polyvalente, CHU Felix-Guyon, allée des Topazes, 97405 Saint-Denis, France. Electronic address: olivier.martinet@chu-reunion.fr.
authors.forename: Olivier
authors.initials: O
authors.lastname: Martinet
authors.affiliation: Réanimation polyvalente, CHU Felix-Guyon, allée des Topazes, 97405 Saint-Denis, France. Electronic address: david.vandroux@chu-reunion.fr.
authors.forename: David
authors.initials: D
authors.lastname: Vandroux
authors.affiliation: Département d'Anesthésie-Réanimation, AP-HP, CHU Bichat-Claude-Bernard, 46, rue Henri-Huchard, 75018 Paris, France. Electronic address: philippe.montravers@bch.aphp.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Montravers
authors.affiliation: Département d'Anesthésie-Réanimation, AP-HP, CHU Bichat-Claude-Bernard, 46, rue Henri-Huchard, 75018 Paris, France. Electronic address: pascal.augustin@bch.aphp.fr.
authors.forename: Pascal
authors.initials: P
authors.lastname: Augustin
mesh_terms: D018806:APACHE; D000368:Aged; D000465:Algorithms; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D015331:Cohort Studies; D003422:Critical Care / Q000592:standards*; D004755:Enterobacteriaceae / Q000187:drug effects; D005260:Female; D005602:France; D005839:Gentamicins / Q000008:administration & dosage* / Q000627:therapeutic use*; D017408:Guidelines as Topic; D006760:Hospitalization; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D018805:Sepsis / Q000188:drug therapy* / Q000401:mortality; D012772:Shock, Septic / Q000188:drug therapy* / Q000401:mortality; D014882:Water-Electrolyte Balance
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins
keywords: Gentamicin; Intensive care unit; Pharmacokinetics/pharmacodynamics; Severe sepsis/septic shock