Increasing Antifungal Drug Resistance in the United States: The example of Candidemia

Background: Candidemia is estimated to be the most common healthcare-associated bloodstream infection in the United States, and can lead to considerable morbidity and mortality. Recent reports of drug resistance to the newer class of antifungals, the echinocandins, as well as multidrug resistance have been reported. However, no nationally notifiable mandatory reporting exists for this infection. In lieu of national surveillance, the most comprehensive surveillance system for candidemia in the United States is conducted through the Emerging Infections Program run by CDC and state partners. Recent findings and trends are reviewed.

Methods: Incident episodes of candidemia were identified through active, population-based laboratory surveillance. In 2008, surveillance began in two U.S. locations where prior surveillance had occurred in the 1990s (metropolitan Atlanta, Georgia area, and Baltimore City and County in Maryland), and expanded to two new locations in 2011 (metropolitan Portland, Oregon area, and Knox County, Tennessee); total population under surveillance was 7.9 million in 2014. Demographic and clinical data were collected for all catchment-area residents with positive blood cultures for Candida spp. Multidrug resistance (MDR) was defined as resistance to both fluconazole and an echinocandin antifungal medication. Incidence rates per 100,000 persons were calculated using census data. 

Results: In 2008, the incidence of candidemia had increased compared with prior surveillance (in Maryland: 33.1 cases per 100,000 vs. 24.1 in the 1990s; Georgia: 14.4 vs. 9.1). From 2008 through 2012, rates declined considerably in these two sites, and from 2012 through 2014 rates remained relatively stable (13.2-15.5 cases per 100,000 people in Maryland, 8.5-9.4 in Georgia). Incidence rates in the other two sites have remained stable during 2011-2014 (8.7-10.7 in Tennessee, 3.4-4.2 in Oregon). Across all sites increases in echinocandin-resistant and MDR Candida have emerged. Most echinocandin-resistant isolates identified were Candida Glabrata (CG), and all but one MDR isolate was CG. The proportion of CG cases with MDR Candida increased from 1.8% to 2.6% from 2008 to 2014.

Conclusions:  Although overall candidemia rates have declined or remained stable, increases in multidrug resistant isolates have been detected in population-based surveillance and was most often seen with CG infections. Continued surveillance is needed to monitor the emergence of MDR Candida.