title: Standard dosing of amikacin and gentamicin in critically ill patients results in variable and subtherapeutic concentrations.
abstract: Low peak plasma concentrations (Cmax) of amikacin and gentamicin are reported in intensive care unit (ICU) patients after administration of the first dose. The present study aimed to describe the proportion of ICU patients in whom an adequate Cmax was achieved throughout the course of therapy. Septic ICU patients with an indication for intravenous amikacin or gentamicin were eligible for inclusion in this single-centre observational study. The first and subsequent doses and the corresponding Cmax values were recorded. The target Cmax was ≥60mg/L for amikacin and ≥30mg/L for gentamicin. Amikacin and gentamicin plasma concentrations were available in 66 and 24 patients, respectively (59±17 years; 79±19kg; height 169±12cm; SAPS II score 46±19). Pulmonary, abdominal and urinary tract infections were diagnosed in 64 patients. Culture-positive infection was confirmed in 65 patients (72%). A target first Cmax was achieved in 17/90 patients (19%). For amikacin, the target Cmax was achieved in 16/66 patients (24%) after the initial dose. In the 50 remaining patients, a change in dosing was performed in 14 patients, leading adequate peak plasma level in 2 patients. For gentamicin, the targeted Cmax was achieved in only 1/24 patient (4%) after the initial dose and was never achieved after the third dose. In conclusion, standard dosing of amikacin or gentamicin led to adequate Cmax in only 19% of patients. Subtherapeutic Cmax were not significantly corrected after subsequent doses.
authors: Service des reanimations, Pôle Anesthésie Réanimation Douleur Urgence, CHU Nîmes, Place du Professeur Robert Debré, 30 029 Nîmes Cedex 9, France; EA 2992, Faculté de Médicine Montpellier Nîmes, Avenue JF Kennedy, 30 000 Nîmes, France.
authors: Claire
authors: C
authors: Roger
authors: Service des reanimations, Pôle Anesthésie Réanimation Douleur Urgence, CHU Nîmes, Place du Professeur Robert Debré, 30 029 Nîmes Cedex 9, France.
authors: Bastian
authors: B
authors: Nucci
authors: Department of Biostatistics, UMR 729 MISTEA, Montpellier University Hospital, Avenue Gaston Giraud, Montpellier 34093, France.
authors: Nicolas
authors: N
authors: Molinari
authors: Service Biostatistique Epidémiologie, Santé Publique Information Médicale, CHU Nîmes, Place du Professeur Robert Debré, 30 029 Nîmes Cedex 9, France.
authors: Sophie
authors: S
authors: Bastide
authors: Service des reanimations, Pôle Anesthésie Réanimation Douleur Urgence, CHU Nîmes, Place du Professeur Robert Debré, 30 029 Nîmes Cedex 9, France.
authors: Gilbert
authors: G
authors: Saissi
authors: Service des reanimations, Pôle Anesthésie Réanimation Douleur Urgence, CHU Nîmes, Place du Professeur Robert Debré, 30 029 Nîmes Cedex 9, France; Service de Réanimation, CH Avignon, 84 000 Avignon, France.
authors: Gael
authors: G
authors: Pradel
authors: Service des reanimations, Pôle Anesthésie Réanimation Douleur Urgence, CHU Nîmes, Place du Professeur Robert Debré, 30 029 Nîmes Cedex 9, France.
authors: Saber
authors: S
authors: Barbar
authors: Service de Pharmacie, CHU Nîmes, Place du Professeur Robert Debré, 30 029 Nîmes Cedex 9, France.
authors: Clément
authors: C
authors: Aubert
authors: Service des reanimations, Pôle Anesthésie Réanimation Douleur Urgence, CHU Nîmes, Place du Professeur Robert Debré, 30 029 Nîmes Cedex 9, France.
authors: Sophie
authors: S
authors: Lloret
authors: Service des reanimations, Pôle Anesthésie Réanimation Douleur Urgence, CHU Nîmes, Place du Professeur Robert Debré, 30 029 Nîmes Cedex 9, France.
authors: Loubna
authors: L
authors: Elotmani
authors: Laboratoire de Biochimie, CHU Nîmes, Place du Professeur Robert Debré, 30 029 Nîmes Cedex 9, France.
authors: Anne
authors: A
authors: Polge
authors: Service des reanimations, Pôle Anesthésie Réanimation Douleur Urgence, CHU Nîmes, Place du Professeur Robert Debré, 30 029 Nîmes Cedex 9, France; EA 2992, Faculté de Médicine Montpellier Nîmes, Avenue JF Kennedy, 30 000 Nîmes, France. Electronic address: jean-yves.lefrant@wanadoo.fr.
authors: Jean-Yves
authors: JY
authors: Lefrant
authors: Burns, Trauma and Critical Care Research Centre, The University of Queensland, Royal Brisbane and Women's Hospital, Herston, Brisbane 4029, QLD, Australia.
authors: Jason A
authors: JA
authors: Roberts
authors: Service des reanimations, Pôle Anesthésie Réanimation Douleur Urgence, CHU Nîmes, Place du Professeur Robert Debré, 30 029 Nîmes Cedex 9, France; EA 2992, Faculté de Médicine Montpellier Nîmes, Avenue JF Kennedy, 30 000 Nîmes, France.
authors: Laurent
authors: L
authors: Muller
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000583:Amikacin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001424:Bacterial Infections / Q000188:drug therapy; D015331:Cohort Studies; D016638:Critical Illness; D005260:Female; D005839:Gentamicins / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006801:Humans; D059413:Intraabdominal Infections / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry*; D018410:Pneumonia, Bacterial / Q000188:drug therapy; D014552:Urinary Tract Infections / Q000188:drug therapy
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins; D000583:Amikacin
keywords: Aminoglycoside; ICU; Peak plasma concentration