88 Antifungal Therapy
Learning Outcomes
- Explain why antifungal therapy is becoming less successful in public health
Just like antibiotics cure bacterial infections, antifungal medications save lives by curing dangerous fungal infections. And just like some bacterial infections are resistant to antibiotics, some fungi no longer respond to the antifungal medications that are designed to cure them. This emerging phenomenon is known as antifungal resistance, and it’s primarily a concern for invasive infections with the fungus Candida.
Although antibiotic-resistant bacterial infections are a widely-recognized public health threat, less is known about the effects of antifungal resistance and the burden of drug-resistant fungal infections. This highlights the need for an improved understanding of the reasons for their emergence, heightened awareness among medical and public health communities about these infections, and greater attention to methods that can be used to prevent and control them.
The Problem
Invasive fungal infections cause substantial morbidity and mortality and are a costly, common problem in healthcare settings. The fungus Candida is the most common cause of healthcare-associated bloodstream infections in the United States.[1] Each case of Candida bloodstream infection (also known as candidemia) is estimated to result in an additional 3 to 13 days of hospitalization and $6,000 to $29,000 in healthcare costs.[2]
What’s also concerning is that some types of Candida are becoming increasingly resistant to first-line and second-line antifungal medications, namely, fluconazole and echinocandins (anidulafungin, caspofungin, and micafungin). Approximately 7% of all Candida bloodstream isolates tested at CDC are resistant to fluconazole, most of which are Candida glabrata.[3], [4] CDC’s surveillance data indicate that the proportion of Candida isolates that are resistant to fluconazole has remained fairly constant over the past twenty years.[5], [6], [7] Echinocandin resistance, however, appears to be on the rise, especially among Candida glabrata. CDC’s surveillance data indicate that up to 8% of Candida glabrata isolates in 2014 may not be susceptible to echinocandins; this proportion nearly doubled from 4% in 2008. This is especially concerning as echinocandins are the mainstay of treatment for Candida glabrata, which already has high levels of resistance to fluconazole.[8]
The stable yet substantial rates of fluconazole resistance and the emergence of echinocandin resistance are concerning because echinocandins are typically used to treat infections caused by C. glabrata, the species that’s most often associated with fluconazole resistance. For multi-drug resistant Candida infections (those that are resistant to both fluconazole and an echinocandin), the few remaining treatment options are expensive and can be toxic for patients who are already very sick. Not surprisingly, there is growing evidence to suggest that patients who have drug-re