Assessment of the National French recommendations regarding the dosing regimen of 8mg/kg of gentamicin in patients hospitalized in intensive care unit.

Introduction: 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 8 mg/kg administered in patients hospitalised in the intensive care unit (ICU). Patients and 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 > 30 mg/L. Twenty-four of 34 patients (71%) had a Cmax > 16 mg/L. Following multivariate analysis, the only factor associated with Cmax < 16 mg/L was a positive fluid balance 24 hours before gentamicin administration (per 1000 mL increment) (OR: 0.37, 95% CI: 0.18-0.77, P = 0.008). Conclusions: These results suggest that a Cmax > 30 mg/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 8 mg/kg in the ICU. A loading dose of 8 mg/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 4 mg/L. A Cmax > 16 mg/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. (C) 2016 Societe francaise d'anesthesie et de reanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.