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
a multicenter, randomized, double-blind, and parallel-group study
Background
Few randomized trials compared antifungals (fluconazole and capsofungin) to placebo empirically in critically ill septic patients. They failed to provide any benefit, however, empirical antifungal therapy is recommended for non immunocompromised critically ill patients with unresolved ICU-acquired sepsis.
No trial has compared empiric antifungal based on colonization
WHAT THEY DID
Compared micafungin 100mg daily with palcebo in critically ill patients with septic shock without invasive fungal infection with suspected invasive candidiasis
WHERE
19 ICUs in France, 235 total patients
INCLUSION CRITERIA
(1) mechanically ventilated at least 5 days (2) with at least 1 colonization site (other than rectal swab or stool) positive for Candida species using traditional culture methods (3) at least 1 additional organ dysfunction;
(4) previous treatment for more than 4 days using broad-spectrum antibacterial agents within the last 7 days; (5) 1 arterial or central vein catheter, and (6) 1 new finding of ICU-acquired sepsis of unknown origin
EXCLUSION CRITERIA
(1) neutrophil count of less than 500/mm3; (2) previous bone marrow or solid organ transplantation; (3) ongoing systemic immunosuppressant agent therapy other than corticosteroids at doses lower than 2 mg/kg/d of prednisolone or equivalent; and (4) antifungal treatment with an echinocandin agent for more than 1 day or with any other antifungal agent for more than 72 hours during the week prior to inclusion
MAIN RESULTS
Day-28 survival was similar between micafungin and placebo groups.
15 (12%) patients in the placebo group and 4 (3%) patients in the micafungin group developed at least 1 new proven invasive fungal infection (P = .008)
The drug was well tolerated with few adverse events.
LIMITATIONS
High risk patients not enrolled.
Dosing was not monitored with drug levels.
BOTTOMLINE
Empiric micafungin does not work in critically ill patient with sepsis, with high risk of fungal infection.
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