Éditeur(s) : HAL CCSD American Medical Association (AMA)
Résumé : International audience
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.
ISSN: 0098-7484

hal-01405822
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01405822
DOI : 10.1001/jama.2016.14655
PUBMED : 27706483

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The chemical investigations of Dicorynia guianensis heartwood led to the isolation of four new indole alkaloids for the first time in this plant. Compound (1) identified as spiroindolone 20,30,40,90-tetrahydrospiro [indoline-3,10pyrido[3,4-b]-indol]-2-one, and compound (3) described as nitrone 1-methyl-4,9-dihydro-3H-pyrido [3,4-b] indole 2-oxide and were isolated for the first time as natural products. ABTS antioxidant activity guided their isolation.
ISSN: 1874-3900

hal-01138910
https://hal.archives-ouvertes.fr/hal-01138910
DOI : 10.1016/j.phytol.2015.03