• Stephan Ehrmann, François Barbier, Julien Demiselle, QuenotJean-PierreJPFrom Centre Hospitalier Régional Universitaire (CHRU) de Tours, Médecine Intensive Réanimation, INSERM Centre d'Investigation Clinique (CIC) 1415, Clinical Research in Intensive Care and Sepsis-Trial Group for Global Evaluation and Rese, Jean-Etienne Herbrecht, Damien Roux, Jean-Claude Lacherade, Mickaël Landais, Philippe Seguin, David Schnell, Anne Veinstein, Philippe Gouin, Sigismond Lasocki, Qin Lu, Gaëtan Beduneau, Martine Ferrandiere, Gaëtan Plantefève, Claire Dahyot-Fizelier, Nader Chebib, Emmanuelle Mercier, Nathalie Heuzé-Vourc'h, Renaud Respaud, Nicolas Gregoire, Denis Garot, Mai-Anh Nay, Ferhat Meziani, Pascal Andreu, Raphaël Clere-Jehl, Noémie Zucman, Marie-Ange Azaïs, Marjorie Saint-Martin, GandonnièreCharlotte SalmonCSFrom Centre Hospitalier Régional Universitaire (CHRU) de Tours, Médecine Intensive Réanimation, INSERM Centre d'Investigation Clinique (CIC) 1415, Clinical Research in Intensive Care and Sepsis-Trial Group for Global Evaluatio, Dalila Benzekri, Hamid Merdji, Elsa Tavernier, and Reva and CRICS-TRIGGERSEP F-CRIN Research Networks.
• From Centre Hospitalier Régional Universitaire (CHRU) de Tours, Médecine Intensive Réanimation, INSERM Centre d'Investigation Clinique (CIC) 1415, Clinical Research in Intensive Care and Sepsis-Trial Group for Global Evaluation and Research in Sepsis (CRICS_TRIGGERSep) French Clinical Research Infrastructure Network (F-CRIN) Research Network (S.E., E.M., D.G., C.S.G.), INSERM, Research Center for Respiratory Diseases (S.E., F.B., N.H.-V., R.R.), the University of Tours (S.E., N.H.-V., R.R.), CHRU de Tours, Réanimation Chirurgicale (M.F.), CHRU de Tours, Pharmacie (R.R.), and CHRU de Tours, INSERM CIC 1415 and Université de Tours et Nantes, Methods in Patient-Centered Outcomes and Health Research, INSERM 1246 (E.T.), Tours, Centre Hospitalier et Universitaire (CHU) d'Orléans, Médecine Intensive Réanimation, Orléans (F.B., M.-A.N., D.B.), Médecine Intensive-Réanimation, Hôpitaux Universitaires de Strasbourg, Nouvel Hôpital Civil and INSERM, Unité Mixte de Recherche (UMR) 1260, Regenerative Nanomedicine, Université de Strasbourg, Faculté de Médecine, Fédération de Médecine Translationnelle de Strasbourg (J.D., F.M., H.M.), and Hôpitaux Universitaires de Strasbourg, Hôpital Hautepierre, Médecine Intensive Réanimation (J.-E.H., R.C.-J.), Strasbourg, the Department of Intensive Care, Burgundy University Hospital and Lipness Team, INSERM Research Center Lipids, Nutrition, Cancer (LNC)-UMR1231 and LabEx LipSTIC, University of Burgundy, and INSERM CIC 1432, Clinical Epidemiology, University of Burgundy (J.-P.Q.), and the Department of Intensive Care, Burgundy University Hospital (P.A.), Dijon, Université Paris Cité, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Louis Mourier, Départements Médico-Universitaires Enseignements et Soins de Proximité, Recherche, Innovation et Territoires (DMU ESPRIT), Service de Médecine Intensive Réanimation, Colombes (D.R., N.Z.), INSERM/French National Center for Scientific Research, Institut Necker Enfants Malades, Université Paris Cité (D.R.), and Multidisciplinary Intensive Care Unit, Department of Anesthesiology and Critical Care, La Pitié-Salpêtrière Hospital, AP-HP, Sorbonne University (Q.L.), Paris, Centre Hospitalier Départemental Vendée, Médecine Intensive Réanimation, La Roche sur Yon (J.-C.L., M.-A.A.), Centre Hospitalier (CH) du Mans, Médecine Intensive Réanimation, Le Mans (M.L., M.S.-M.), CHU de Rennes, Réanimation Chirurgicale, Rennes (P.S.), CH Angoulême, Médecine Intensive Réanimation, Angoulême (D.S.), CHU de Poitiers, Médecine Intensive Réanimation (A.V.), Université de Poitiers, INSERM, Pharmacologie des Anti-Infectieux et Antibiorésistance (PHAR2), Unité 1070 and CHU de Poitiers, Anesthésie-Réanimation-Médecine Péri-Opératoire, F-86000 (C.D.-F.), Université de Poitiers, PHAR2 INSERM U1070 (N.G.), and CHU de Poitiers, Service de Toxicologie et Pharmacologie (N.G.). Poitiers, CHU de Rouen, Réanimation Chirurgicale (P.G.), University Rouen Normandie, Normandie University, Groupe de Recherche sur le Handicap Ventilatoire et Neurologique, Unité de recherche 3830 and Intensive Care Medicine, Rouen University Hospital (G.B.), Rouen, CHU Angers, Réanimation Chirurgicale, Angers (S.L.), CH d'Argenteuil, Réanimation Polyvalente, Argenteuil (G.P.), and Réanimation Médicale, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon (N.C.) - all in France; and the Department of Emergency Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China (Q.L.).
• N. Engl. J. Med. 2023 Nov 30; 389 (22): 205220622052-2062.

BackgroundWhether preventive inhaled antibiotics may reduce the incidence of ventilator-associated pneumonia is unclear.MethodsIn this investigator-initiated, multicenter, double-blind, randomized, controlled, superiority trial, we assigned critically ill adults who had been undergoing invasive mechanical ventilation for at least 72 hours to receive inhaled amikacin at a dose of 20 mg per kilogram of ideal body weight once daily or to receive placebo for 3 days. The primary outcome was a first episode of ventilator-associated pneumonia during 28 days of follow-up. Safety was assessed.ResultsA total of 850 patients underwent randomization, and 847 were included in the analyses (417 assigned to the amikacin group and 430 to the placebo group). All three daily nebulizations were received by 337 patients (81%) in the amikacin group and 355 patients (83%) in the placebo group. At 28 days, ventilator-associated pneumonia had developed in 62 patients (15%) in the amikacin group and in 95 patients (22%) in the placebo group (difference in restricted mean survival time to ventilator-associated pneumonia, 1.5 days; 95% confidence interval [CI], 0.6 to 2.5; P = 0.004). An infection-related ventilator-associated complication occurred in 74 patients (18%) in the amikacin group and in 111 patients (26%) in the placebo group (hazard ratio, 0.66; 95% CI, 0.50 to 0.89). Trial-related serious adverse effects were seen in 7 patients (1.7%) in the amikacin group and in 4 patients (0.9%) in the placebo group.ConclusionsAmong patients who had undergone mechanical ventilation for at least 3 days, a subsequent 3-day course of inhaled amikacin reduced the burden of ventilator-associated pneumonia during 28 days of follow-up. (Funded by the French Ministry of Health; AMIKINHAL ClinicalTrials.gov number, NCT03149640; EUDRA Clinical Trials number, 2016-001054-17.).Copyright © 2023 Massachusetts Medical Society.

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