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.
Timsit JF(1), Azoulay E(2), Schwebel C(3), Charles PE(4), Cornet M(5), Souweine
B(6), Klouche K(7), Jaber S(8), Trouillet JL(9), Bruneel F(10), Argaud L(11),
Cousson J(12), Meziani F(13), Gruson D(14), Paris A(15), Darmon M(16),
Garrouste-Orgeas M(17), Navellou JC(18), Foucrier A(19), Allaouchiche B(20), Das
V(21), Gangneux JP(22), Ruckly S(23), Maubon D(5), Jullien V(24), Wolff M(1);
EMPIRICUS Trial Group.
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.
DOI: 10.1001/jama.2016.14655
PMID: 27706483 [Indexed for MEDLINE]
- Intensive Care Med. 2016 Dec;42(12):2098-2100. doi: 10.1007/s00134-016-4448-7.
Epub 2016 Jul 18.
De-escalation of pivotal beta-lactam in ventilator-associated pneumonia does not
impact outcome and marginally affects MDR acquisition.
Weiss E(1), Zahar JR(2), Garrouste-Orgeas M(3), Ruckly S(4), Essaied W(5),
Schwebel C(6), Timsit JF(5)(7); OUTCOMEREA Study Group.
MESSAGES:
Après ajustement sur les facteurs confondant, la désescalade vers une antibiothérapie étroite n’impacte que de manière très marginale le risque d’émergence de bacilles à gram négatifs résistants.
DOI: 10.1007/s00134-016-4448-7
PMID: 27430221