Oct 252017

The antifungal micafungin is often given empirically to patients in ICUs with sepsis who are also at high risk for invasive fungal infections. IDSA guidelines endorse the use of empiric antifungals for patients with unresolving ICU-acquired sepsis, but any benefits of this are unknown. A randomized trial published in JAMA sheds light on the practice.

French investigators at 19 ICUs randomized 260 patients with sepsis acquired in the ICU who were at high risk for invasive fungal infections to receive either micafungin or placebo. Patients had multiple sites of Candida colonization (e.g., skin, sputum, but excluding stool or rectal swabs), had received broad spectrum antibiotics, and had central lines and multiple organ failure, but were not neutropenic, transplant recipients, or on immune suppression.

At 28 days, 68% of patients taking micafungin were alive without an invasive fungal infection (composite endpoint, defined as negative fungal blood cultures), vs. 60% in the placebo group (not statistically significant). Nor was there a statistically significant benefit in patients with high levels of the fungal marker (1-3)-β-D-glucan (i.e., a high burden of Candida colonization) or high SOFA organ failure scores.

However, empiric micafungin did result in fewer invasive fungal infections (3% vs 12% with placebo), which was statistically significant. The hazard ratios (higher = better in this trial) were 1.4 - 1.6 in the sicker patients with higher fungal markers, and the low end of the confidence interval for benefit approached 1.0 in the sickest patients with SOFA scores >8.

This was a negative trial, and echoed an 2014 trial testing caspofungin among 222 patients. But considering that in both trials patients receiving empiric antifungals had fewer invasive fungal infections, there is little here to dissuade the nervous physician from prescribing micafungin to very ill patients with ICU-acquired sepsis and risk factors for invasive fungal infections.

Authors disclosed financial relationships with pharmaceutical companies including Astellas, which manufactures micafungin and helped fund the trial.

Read more:

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 Trial. JAMA. 2016;316(15):1555-1564.

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Empiric micafungin didn’t save lives in ICU-acquired sepsis