Echinocandin resistance in Candida glabrata bloodstream infection 2009-2015 at a single institution

Background:

Candida is a frequent cause of healthcare associated bloodstream infection (BSI). There are growing, but sporadic, reports of echinocandin resistance (ECH-R) via mutations in the FKS subunits of the glucan synthase gene. This has been most frequently observed in C. glabrata, which already demonstrates increased fluconazole resistance. This creates a difficult clinical scenario given that the time to appropriate antifungal therapy remains an important determinant in the outcome of Candida BSI.

Methods:

All clinical isolates of Candida have been stored at the University of Alabama at Birmingham since 2003. All isolates were tested for micafungin resistance using broth microdilution. All C. glabrata isolates were referred to the Centers for Disease Control and Prevention for genetic sequencing of FKS 1 and 2. We reviewed patients with BSI caused by C. glabrata with decreased susceptibility to micafungin. Additionally, we assessed 30-day mortality in all episodes of C. glabrata BSI during the same years.

Results:

The first C. glabrata BSI with decreased susceptibility to micafungin occurred in 2009. Among 303 isolates, 7 were ECH-R between 2009 and 2015 (Figure 1). The minimum inhibitory concentration (MIC) ranged from 0.125 to 2mcg/ml. 3 of 5 isolates were found to have FKS mutations; 2 tests are pending. Only 1 isolate with a sensitive MIC had an FKS mutation. Mean age was 39 years. More than half of episodes occurred in inpatients with total parenteral nutrition, intravenous antibiotics, a central venous catheter, and prior echinocandin exposure.   Mean APACHE-II score was 20. Mortality at 30 days was 71%, compared to all other C. glabrata BSIs with 30-day mortality of 34%.

Conclusion:

Time to effective antifungal therapy for candidemia is often delayed, and this has a significant impact on mortality. The latest IDSA guidelines for the treatment of candidemia recommend initial therapy with an echinocandin until fluconazole sensitivity can be demonstrated. With increasing reports of echinocandin resistance in C. glabrata, it is important to know accurate rates at individual sites. We demonstrated cases present since 2009, but remain unusual at our institution. Further investigation into the impact of ECH-R on clinical outcomes is needed.

Figure 1