Abstract
BackgroundThe 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.MethodsThis 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.DiscussionThis study will help to provide guidelines for treating non-immunocompromized patients with fungal colonization multiple organ failure and sepsis of unknown origin.Trial registrationClinicaltrials.gov number NCT01773876
Highlights
The potential interest of antifungal treatment of non-immunocompromized patients with sepsis, extra-digestive Candida colonization and multiple organ failure is unknown
Regarding benefits to expect from empirical or preemptive systemic antifungal therapy (SAT) in critically ill non-immunocompromized patients, the current literature is inconclusive and trials demonstrating the efficacy of SAT in colonized patients with unresolved sepsis and organ dysfunction are warranted
Randomized control trials (RCTs) have demonstrated that SAT is effective in cases of proven invasive fungal infection, but these latter represent only 15 to 20% of the SAT prescribed in ICU [12,35]
Summary
This prospective multicenter, double blind, randomized-controlled trial is conducted in 23 French Intensive Care Units. 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. 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. Pharmacokinetics of micafungin in enrolled patients will be measured and evolution of fungal biomarkers and susceptibility profiles of infecting fungi will be followed
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