Inhaled Amikacin to Prevent Ventilator-Associated Pneumonia

被引：34

作者：

Ehrmann, Stephan ^{[1
,2
,3
]}

Barbier, Francois ^{[2
,8
]}

Demiselle, Julien ^{[9
,10
]}

Quenot, Jean-Pierre ^{[12
,13
,14
]}

Herbrecht, Jean-Etienne ^{[11
]}

Roux, Damien ^{[16
,17
]}

Lacherade, Jean-Claude ^{[19
]}

Landais, Mickael ^{[20
]}

Seguin, Philippe ^{[21
]}

Schnell, David

Veinstein, Anne ^{[22
]}

Gouin, Philippe ^{[27
]}

Lasocki, Sigismond ^{[30
]}

Lu, Qin ^{[18
,33
]}

Beduneau, Gaetan ^{[28
,29
]}

Ferrandiere, Martine ^{[4
]}

Plantefeve, Gaetan ^{[31
]}

Dahyot-Fizelier, Claire ^{[23
,24
]}

Chebib, Nader ^{[32
]}

Mercier, Emmanuelle ^{[1
]}

Heuze-Vourc'h, Nathalie ^{[2
,3
]}

Respaud, Renaud ^{[2
,3
,5
]}

Gregoire, Nicolas ^{[25
,26
]}

Garot, Denis ^{[1
,3
]}

Nay, Mai-Anh ^{[8
]}

Meziani, Ferhat ^{[9
,10
]}

Andreu, Pascal ^{[15
]}

Clere-Jehl, Raphael ^{[11
]}

Zucman, Noemie ^{[16
]}

Azais, Marie-Ange ^{[19
]}

Saint-Martin, Marjorie ^{[20
]}

Gandonniere, Charlotte Salmon ^{[1
,3
]}

Benzekri, Dalila ^{[8
]}

Merdji, Hamid ^{[9
,10
]}

Tavernier, Elsa ^{[6
,7
]}

机构：

[1] Ctr Hosp Reg Univ CHRU Tours, INSERM Ctr Invest Clin CIC 1415, Clin Res Intens Care & Sepsis Trial Grp Global Ev, Med Intens Reanim,French Clin Res Infrastruct,Res, Tours, France

[2] INSERM, Res Ctr Resp Dis, Paris, France

[3] Univ Tours, Tours, France

[4] CHRU Tours, Reanimat Chirurg, Tours, France

[5] CHRU Tours, Pharm, Tours, France

[6] CHRU Tours, INSERM CIC 1415, Tours, France

[7] Univ Tours & Nantes, Methods Patient Ctr Outcomes & Hlth Res, INSERM 1246, Tours, France

[8] Ctr Hosp & Univ CHU Orleans, Med Intens Reanimat, Orleans, France

[9] Hop Univ Strasbourg, Nouvel Hop Civil, Med Intens Reanimat, Strasbourg, France

[10] Univ Strasbourg, Fac Med, Unite Mixte Rech UMR 1260, INSERM, Strasbourg, France

[11] Hop Univ Strasbourg, Med Intens Reanimat, Hop Hautepierre, Strasbourg, France

[12] Burgundy Univ Hosp & Lipness Team, Dept Intens Care, INSERM, Res Ctr Lipids Nutr Canc LNC,UMR 1231, Dijon, France

[13] Univ Burgundy, LabEx LipST, Dijon, France

[14] Univ Burgundy, Clin Epidemiol, INSERM CIC 1432, Dijon, France

[15] Burgundy Univ Hosp, Dept Intens Care, Dijon, France

[16] Univ Paris Cite, Hop Louis Mourier, AP HP, Dept Med Univ Enseignements & Soins Proxim,Rech I, Colombes, France

[17] Univ Paris Cite, Inst Necker Enfants Malad, French Natl Ctr Sci Res, INSERM, Paris, France

[18] Sorbonne Univ, Pitie Salpetriere Hosp, Dept Anesthesiol & Crit Care, Multidisciplinary Intens Care Unit, Paris, France

[19] Ctr Hosp Dept Vendee, Med Intens Reanimat, La Roche Sur Yon, France

[20] Ctr Hosp CH Mans, Med Intens Reanimat, Le Mans, France

[21] CHU Rennes, Reanimat Chirurg, Rennes, France

[22] CHU Poitiers, Med Intens Reanimat, Poitiers, France

[23] Univ Poitiers, INSERM, Unite 1070, Pharmacol Antiinfect & Antibioresistance PHAR2, F-86000 Poitiers, France

[24] CHU Poitiers, Anesthesie Reanimat Med Peri Operat, F-86000 Poitiers, France

[25] Univ Poitiers, PHAR2 INSERM U1070, Poitiers, France

[26] CHU Poitiers, Serv Toxicol & Pharmacol, Poitiers, France

[27] CHU Rouen, Reanimat Chirurg, Rouen, France

[28] Univ Rouen Normandie, Normandie Univ, Grp Rech Handicap Ventilatoire & Neurol, Unite Rech 3830, Normandie, France

[29] Rouen Univ Hosp, Intens Care Med, Rouen, France

[30] CHU Angers, Reanimat Chirurg, Angers, France

[31] CH Argenteuil, Reanimat Polyvalente, Argenteuil, France

[32] Hosp Civils Lyon, Hop Croix Rousse, Reanimat Med, Lyon, France

[33] Zhejiang Univ, Affiliated Hosp 2, Dept Emergency Med, Sch Med, Hangzhou, Peoples R China

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2023年 / 389卷 / 22期

关键词：

DOSE NEBULIZED AMIKACIN; RESPIRATORY-TRACT; DOUBLE-BLIND; PHARMACOKINETICS; ANTIBIOTICS; MORTALITY; COLISTIN; ADULTS; IMPACT; RATES;

D O I：

10.1056/NEJMoa2310307

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 (82%) 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.) In a randomized trial involving critically ill patients who had undergone mechanical ventilation for 3 days, a 3-day course of inhaled amikacin reduced the burden of ventilator-associated pneumonia.

引用

页码：2052 / 2062

页数：11

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