Empirical Micafungin Treatment and Survival Without Invasive Fungal Infection in Adults With ICU-Acquired Sepsis, Candida Colonization, and Multiple Organ Failure The EMPIRICUS Randomized Clinical Trial - Université de Rennes Access content directly
Journal Articles Journal of the American Medical Association Year : 2016

Empirical Micafungin Treatment and Survival Without Invasive Fungal Infection in Adults With ICU-Acquired Sepsis, Candida Colonization, and Multiple Organ Failure The EMPIRICUS Randomized Clinical Trial

1 Département d'anesthésie-réanimation[Montpellier]
2 PhyMedExp - Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046]
3 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
4 CHU Pitié-Salpêtrière [AP-HP]
5 ICAN - Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases
6 Service de réanimation [CH Versailles]
7 Hôpital Edouard Herriot [CHU - HCL]
8 Service de réanimation médicale
9 HIFIH - Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques
10 LBP - Laboratoire de Biophotonique et Pharmacologie - UMR 7213
11 LOUVAIN - Endocrino - Département d'Endocrinologie et Nutrition
12 CIC - Grenoble
13 CSE
14 Epidémiologie pronostique des cancers et affections graves
15 Service de Réanimation médicale [CHRU Besançon]
16 Reanimation Médicale et Infectieuse [Bichat]
17 Service de Réanimation
18 Service de réanimation médicale
19 Irset - Institut de recherche en santé, environnement et travail
20 Service de Parasitologie-Mycologie [Rennes]
21 Institut de Biologie et Pathologie
22 U1129 - Epilepsies de l'Enfant et Plasticité Cérébrale
23 NRL - Naval Research Laboratory
24 Unité de Soins Intensifs et de Maladies Infectieuses
25 IAME (UMR_S_1137 / U1137) - Infection, Anti-microbiens, Modélisation, Evolution
26 AP-HP - Hopital Saint-Louis [AP-HP]
27 Service de Réanimation Médicale [Grenoble]
28 Service de Réanimation Médicale (CHU de Dijon)
29 TheREx
30 LMGE - Laboratoire Microorganismes : Génome et Environnement
Joel Cousson
  • Function : Author
  • PersonId : 946881
Adeline Paris
  • Function : Author
Michael Darmon
CSE
Vincent Das
  • Function : Author
  • PersonId : 910820
Danièle Maubon
Élie Azoulay
Muriel Cornet
  • Function : Author

Abstract


Importance Although frequently used in treating intensive care unit (ICU) patients with sepsis, empirical antifungal therapy, initiated for suspected fungal infection, has not been shown to improve outcome.

Objective To determine whether empirical micafungin reduces invasive fungal infection (IFI)–free survival at day 28.

Design, Setting, and Participants Multicenter double-blind placebo-controlled study of 260 nonneutropenic, nontransplanted, critically ill patients with ICU-acquired sepsis, multiple Candida colonization, multiple organ failure, exposed to broad-spectrum antibacterial agents, and enrolled between July 2012 and February 2015 in 19 French ICUs.

Interventions Empirical treatment with micafungin (100 mg, once daily, for 14 days) (n = 131) vs placebo (n = 129).

Main Outcomes and Measures The primary end point was survival without proven IFI 28 days after randomization. Key secondary end points included new proven fungal infections, survival at day 28 and day 90, organ failure, serum (1-3)-β-D-glucan level evolution, and incidence of ventilator-associated bacterial pneumonia.

Results Among 260 patients (mean age 63 years; 91 [35%] women), 251 (128, micafungin group; 123, placebo group) were included in the modified intent-to-treat analysis. Median values were 8 for Sequential Organ Failure Assessment (SOFA) score, 3 for number of Candida-colonized sites, and 99 pg/mL for level of (1-3)-β-D-glucan. On day 28, there were 82 (68%) patients in the micafungin group vs 79 (60.2%) in the placebo group who were alive and IFI free (hazard ratio [HR], 1.35 [95% CI, 0.87-2.08]). Results were similar among patients with a (1-3)-β-D-glucan level of greater than 80 pg/mL (n = 175; HR, 1.41 [95% CI, 0.85-2.33]). Day-28 IFI–free survival in patients with a high SOFA score (>8) was not significantly different when compared between the micafungin vs placebo groups (HR, 1.69 [95% CI, 0.96-2.94]). Use of empirical micafungin decreased the rate of new invasive fungal infection in 4 of 128 patients (3%) in the micafungin group vs placebo (15/123 patients [12%]) (P = .008).

Conclusions and Relevance Among nonneutropenic critically ill patients with ICU-acquired sepsis, Candida species colonization at multiple sites, and multiple organ failure, empirical treatment with micafungin, compared with placebo, did not increase fungal infection–free survival at day 28.

Trial Registration clinicaltrials.gov Idenitfier: NCT01773876
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Dates and versions

hal-01405822 , version 1 (30-11-2016)

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Kada Klouche, Samir Jaber, Jean-Louis Trouillet, Fabrice Bruneel, Laurent Argaud, et al.. Empirical Micafungin Treatment and Survival Without Invasive Fungal Infection in Adults With ICU-Acquired Sepsis, Candida Colonization, and Multiple Organ Failure The EMPIRICUS Randomized Clinical Trial. Journal of the American Medical Association, 2016, 316 (15), pp.1555--1564. ⟨10.1001/jama.2016.14655⟩. ⟨hal-01405822⟩
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