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

Kada Klouche 1 Samir Jaber 2 Jean-Louis Trouillet 3, 4 Fabrice Bruneel 5 Laurent Argaud 6 Joel Cousson 7 Ferhat Meziani 8, 9 Didier Gruson 10 Adeline Paris 11 Michael Darmon 12 Maïté Garrouste-Orgeas 13 Jean-Christophe Navellou 14 Arnaud Foucrier 15 Bernard Allaouchiche 16 Vincent Das 17 Jean-Pierre Gangneux 18, 19 Stephane Ruckly 13 Danièle Maubon 20 Vincent Jullien 21 Michel Wolff 22 Jean-François Timsit 23, 24 Élie Azoulay 25 Carole Schwebel 26 Pierre Emmanuel Charles 27 Muriel Cornet 28 Bertrand Souweine 29
12 CSE
CESSP - Centre européen de sociologie et de science politique
28 TheREx
TIMC-IMAG - Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525
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 (100mg, once daily, for 14 days) (n = 131) vs placebo (n = 129). MAIN OUTCOMES AND MEASURES The primary end pointwas 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)-beta-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)-beta-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)-beta-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.
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Submitted on : Wednesday, November 30, 2016 - 3:11:42 PM
Last modification on : Tuesday, July 16, 2019 - 1:32:58 AM

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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, American Medical Association (AMA), 2016, 316 (15), pp.1555--1564. ⟨10.1001/jama.2016.14655⟩. ⟨hal-01405822⟩

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