Nicolas Allou1, Jérôme Allyn2, Yaël Levy3, Astrid Bouteau4, Marie Caujolle5, Benjamin Delmas6, Dorothée Valance7, Caroline Brulliard8, Olivier Martinet9, David Vandroux10, Philippe Montravers11, Pascal Augustin12. 1. Réanimation polyvalente, CHU Felix-Guyon, allée des Topazes, 97405 Saint-Denis, France. Electronic address: nicolas.allou@hotmail.fr. 2. Réanimation polyvalente, CHU Felix-Guyon, allée des Topazes, 97405 Saint-Denis, France. Electronic address: allyn.jer@gmail.com. 3. Réanimation polyvalente, CHU Felix-Guyon, allée des Topazes, 97405 Saint-Denis, France. Electronic address: l.yael@hotmail.fr. 4. Département d'Anesthésie-Réanimation, AP-HP, CHU Bichat-Claude-Bernard, 46, rue Henri-Huchard, 75018 Paris, France. Electronic address: astridbouteau@gmail.com. 5. Réanimation polyvalente, CHU Felix-Guyon, allée des Topazes, 97405 Saint-Denis, France. Electronic address: caujollemarie@hotmail.com. 6. Réanimation polyvalente, CHU Felix-Guyon, allée des Topazes, 97405 Saint-Denis, France. Electronic address: benjamindelmas.desar@yahoo.fr. 7. Réanimation polyvalente, CHU Felix-Guyon, allée des Topazes, 97405 Saint-Denis, France. Electronic address: dorothee.valance@gmail.com. 8. Réanimation polyvalente, CHU Felix-Guyon, allée des Topazes, 97405 Saint-Denis, France. Electronic address: carolinebrulliard@gmail.com. 9. Réanimation polyvalente, CHU Felix-Guyon, allée des Topazes, 97405 Saint-Denis, France. Electronic address: olivier.martinet@chu-reunion.fr. 10. Réanimation polyvalente, CHU Felix-Guyon, allée des Topazes, 97405 Saint-Denis, France. Electronic address: david.vandroux@chu-reunion.fr. 11. Département d'Anesthésie-Réanimation, AP-HP, CHU Bichat-Claude-Bernard, 46, rue Henri-Huchard, 75018 Paris, France. Electronic address: philippe.montravers@bch.aphp.fr. 12. Département d'Anesthésie-Réanimation, AP-HP, CHU Bichat-Claude-Bernard, 46, rue Henri-Huchard, 75018 Paris, France. Electronic address: pascal.augustin@bch.aphp.fr.
Abstract
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 8mg/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>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.
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 8mg/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>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: N Allou; Y Charifou; P Augustin; T Galas; D Valance; L Corradi; O Martinet; D Vandroux; J Allyn Journal: Eur J Clin Microbiol Infect Dis Date: 2016-05-03 Impact factor: 3.267
Authors: Rajbharan Yadav; Jürgen B Bulitta; Elena K Schneider; Beom Soo Shin; Tony Velkov; Roger L Nation; Cornelia B Landersdorfer Journal: Antimicrob Agents Chemother Date: 2017-11-22 Impact factor: 5.191
Authors: Caspar J Hodiamont; Annemieke K van den Broek; Suzanne L de Vroom; Jan M Prins; Ron A A Mathôt; Reinier M van Hest Journal: Clin Pharmacokinet Date: 2022-06-27 Impact factor: 5.577