Claire Roger1,2, Benjamin Louart3,4, Loubna Elotmani3,4, Greg Barton5, Leslie Escobar6, Despoina Koulenti7,8, Jeffrey Lipman4,7,9, Marc Leone10, Laurent Muller3,4, Caroline Boutin3, Julien Amour11, Iouri Banakh12, Joel Cousson13, Jeremy Bourenne14, Jean-Michel Constantin15, Jacques Albanese16, Jason A Roberts4,7,9,17, Jean-Yves Lefrant3,4. 1. Department of Intensive Care Medicine, Division of Anesthesiology, Intensive Care, Pain and Emergency Medicine, Nîmes University Hospital, Place du Professeur Robert Debré, 30 029, Nîmes cedex 9, France. claire.roger@chu-nimes.fr. 2. Equipe D, Caractéristiques Féminines Des Interfaces Vasculaires (IMAGINE), Faculté de Médecine, Univ Montpellier, 2992, Montpellier, France. claire.roger@chu-nimes.fr. 3. Department of Intensive Care Medicine, Division of Anesthesiology, Intensive Care, Pain and Emergency Medicine, Nîmes University Hospital, Place du Professeur Robert Debré, 30 029, Nîmes cedex 9, France. 4. Equipe D, Caractéristiques Féminines Des Interfaces Vasculaires (IMAGINE), Faculté de Médecine, Univ Montpellier, 2992, Montpellier, France. 5. St Helens and Knowsley Hospitals NHS Trust, Liverpool, UK. 6. Faculty of Medicine, Universidad de Chile, Santiago, Chile. 7. The University of Queensland Centre for Clinical Research, The University of Queensland, Brisbane, Australia. 8. Second Critical Care Department, Attikon University Hospital, Athens, Greece. 9. Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, Australia. 10. Department of Anesthesiology and Intensive Care Medicine, University Hospital of Marseille, Marseille, France. 11. Institute of Perfusion, Critical Care Medicine and Anesthesiology in Cardiac Surgery (IPRA), Hôpital Privé Jacques Cartier, Massy, France. 12. Frankston Hospital, Frankston, VIC, Australia. 13. Department of Anesthesiology and Intensive Care Medicine, University Hospital of Reims, Reims, France. 14. Department of Emergency and Intensive Care Medicine, University Hospital of Marseille, Hôpital de La Timone, Marseille, France. 15. Department of Anesthesiology and Intensive Care Medicine, University Hospital of Clermont-Ferrand, Clermont-Ferrand, France. 16. Department of Anesthesiology and Intensive Care Medicine, University Hospital of Marseille, Hôpital de La Conception, Marseille, France. 17. Pharmacy Department, Royal Brisbane and Women's Hospital, Brisbane, Australia.
Abstract
BACKGROUND: While aminoglycosides (AG) have been used for decades, debate remains on their optimal dosing strategy. We investigated the international practices of AG usage specifically regarding dosing and therapeutic drug monitoring (TDM) in critically ill patients. We conducted a prospective, multicentre, observational, cohort study in 59 intensive-care units (ICUs) in 5 countries enrolling all ICU patients receiving AG therapy for septic shock. RESULTS: We enrolled 931 septic ICU patients [mean ± standard deviation, age 63 ± 15 years, female 364 (39%), median (IQR) SAPS II 51 (38-65)] receiving AG as part of empirical (761, 84%) or directed (147, 16%) therapy. The AG used was amikacin in 614 (66%), gentamicin in 303 (33%), and tobramycin in 14 (1%) patients. The median (IQR) duration of therapy was 2 (1-3) days, the number of doses was 2 (1-2), the median dose was 25 ± 6, 6 ± 2, and 6 ± 2 mg/kg for amikacin, gentamicin, and tobramycin respectively, and the median dosing interval was 26 (23.5-43.5) h. TDM of Cmax and Cmin was performed in 437 (47%) and 501 (57%) patients, respectively, after the first dose with 295 (68%) patients achieving a Cmax/MIC > 8 and 353 (71%) having concentrations above Cmin recommended thresholds. The ICU mortality rate was 27% with multivariable analysis showing no correlation between AG dosing or pharmacokinetic/pharmacodynamic target attainment and clinical outcomes. CONCLUSION: Short courses of high AG doses are mainly used in ICU patients with septic shock, although wide variability in AG usage is reported. We could show no correlation between PK/PD target attainment and clinical outcome. Efforts to optimize the first AG dose remain necessary. Trial registration Clinical Trials, NCT02850029, registered on 29th July 2016, retrospectively registered, https://www.clinicaltrials.gov.
BACKGROUND: While aminoglycosides (AG) have been used for decades, debate remains on their optimal dosing strategy. We investigated the international practices of AG usage specifically regarding dosing and therapeutic drug monitoring (TDM) in critically illpatients. We conducted a prospective, multicentre, observational, cohort study in 59 intensive-care units (ICUs) in 5 countries enrolling all ICU patients receiving AG therapy for septic shock. RESULTS: We enrolled 931 septic ICU patients [mean ± standard deviation, age 63 ± 15 years, female 364 (39%), median (IQR) SAPS II 51 (38-65)] receiving AG as part of empirical (761, 84%) or directed (147, 16%) therapy. The AG used was amikacin in 614 (66%), gentamicin in 303 (33%), and tobramycin in 14 (1%) patients. The median (IQR) duration of therapy was 2 (1-3) days, the number of doses was 2 (1-2), the median dose was 25 ± 6, 6 ± 2, and 6 ± 2 mg/kg for amikacin, gentamicin, and tobramycin respectively, and the median dosing interval was 26 (23.5-43.5) h. TDM of Cmax and Cmin was performed in 437 (47%) and 501 (57%) patients, respectively, after the first dose with 295 (68%) patients achieving a Cmax/MIC > 8 and 353 (71%) having concentrations above Cmin recommended thresholds. The ICU mortality rate was 27% with multivariable analysis showing no correlation between AG dosing or pharmacokinetic/pharmacodynamic target attainment and clinical outcomes. CONCLUSION: Short courses of high AG doses are mainly used in ICU patients with septic shock, although wide variability in AG usage is reported. We could show no correlation between PK/PD target attainment and clinical outcome. Efforts to optimize the first AG dose remain necessary. Trial registration Clinical Trials, NCT02850029, registered on 29th July 2016, retrospectively registered, https://www.clinicaltrials.gov.
Entities:
Keywords:
Aminoglycoside; Antibiotics; ICU; PK/PD; Therapeutic drug monitoring
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