Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
BACKGROUND: The potential interest of antifungal treatment of non-immunocompromized patients with sepsis, extra-digestive Candida colonization and multiple organ failure is unknown. It represents three-quarters of antifungals prescribed in Intensive Care Units. It may allow early treatment of invasive fungal infection in the incubation phase but expose patients to unnecessary antifungal treatments with subsequent cost and fungal selection pressure. As early diagnostic tests for invasive candidiasis are still considered to be insufficient, the potential interest in this strategy needs to be demonstrated. METHODS: This prospective multicenter, double blind, randomized-controlled trial is conducted in 23 French Intensive Care Units. All adult patients, mechanically ventilated for more than four days with sepsis of unknown origin and with at least one extradigestive fungal colonization site and multiple organ failure are eligible for randomization. Patients with proven invasive candidiasis are not included. After a complete mycological screening, patients are allocated to receive micafungin 100 mg intravenously once a day or placebo for 14 days. We plan to enroll 260 patients. The main objective is to demonstrate that micafungin increases survival of patients without invasive candidiasis at day 28 as compared to placebo. Other outcomes include day 28 and 90 survival and organ failure evolution. Additionally, pharmacokinetics of micafungin in enrolled patients will be measured and evolution of fungal biomarkers and susceptibility profiles of infecting fungi will also be followed. DISCUSSION: This study will help to provide guidelines for treating non-immunocompromized patients with fungal colonization multiple organ failure and sepsis of unknown origin.Trial registration: Clinicaltrials.gov number NCT01773876.
ISSN: 1745-6215

inserm-00913515
http://www.hal.inserm.fr/inserm-00913515
http://www.hal.inserm.fr/inserm-00913515/document
http://www.hal.inserm.fr/inserm-00913515/file/1745-6215-14-399.pdf
PUBMED : 24261608

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 Oxford University Press (OUP)
Résumé : International audience
ISSN: 0305-7453

hal-01470808
https://hal.archives-ouvertes.fr/hal-01470808
DOI : 10.1093/jac/dkw352
PUBMED : 27609051