The EMPIRICUS trial

From a recent issue of JAMA:

Question Does empirical antifungal therapy increase invasive fungal infection–free survival at day 28 in nonneutropenic critically ill patients with sepsis, multiple Candida colonization, and multiple organ failure exposed to broad-spectrum antibacterials?

Findings In this randomized clinical trial of 260 adults, there was no significant difference in the rate of survivors without any fungal infection at day 28 between micafungin-treated (87/128 [68%]) and placebo-treated (74/123 [60.2%]) groups.

Meaning The use of micafungin as a routine empirical treatment in critically ill patients with suspected fungal infection did not improve fungal infection–free survival at 28 days.

These were patients with hospital acquired suspected infections with multiple risk factors for invasive candida infection (apart from neutropenia and certain other forms of severe immunosuppression). The practice of using antifungals in such patients is widespread. This may be practice changing, though some caveats were pointed out in a related editorial:

The study was well powered to assess difference in mortality between groups and the results are largely generalizable to critically ill patients with characteristics similar to the study inclusion criteria. Nonsignificant improvement in survival was noted among patients with high Sequential Organ Failure Assessment scores, which may suggest that certain critically ill subgroups may benefit from empirical therapy. Additionally, there was low participation among patients with postoperative gastrointestinal leakage and acute necrotizing pancreatitis, among which there is a high risk of invasive fungal infection. Previous studies have shown surgical patients may benefit from empirical therapy.

Based on the above, the “empirical” use of antifungal therapy in such patients may need to be more targeted. (The quotation marks point out that the use of antifungal agents such as is described herein is based more on theory and rationale than evidence and so is hardly empirical).