Addressing the Threat of Candida Infections Through Resistance and Management

Candida species are the leading cause of fungal infections in hospitalized patients, contributing significantly to morbidity and mortality. Invasive candidiasis, including candidemia, primarily affects immunocompromised or critically ill individuals, while mucocutaneous candidiasis, such as oral thrush and vulvovaginal candidiasis, can occur in otherwise healthy individuals. While mucocutaneous forms are not typically life-threatening, they can cause discomfort and complications, especially in patients with underlying conditions like diabetes or those on immunosuppressive therapies.

New host factors and antifungal resistance drive the rise of difficult-to-treat Candida infections. Pathogens such as Candida auris and fluconazole-resistant Candida parapsilosis pose global health risks. Recent taxonomic revisions have reclassified several Candida species, leading to potential confusion in clinical practice. Current management guidelines are limited in scope, with insufficient coverage of emerging pathogens and new treatment options.

In an email interview with Oliver A Cornely, professor of translational research at Cluster of Excellence, University of Cologne, he discussed how healthcare providers can best address the rise of Candida auris and fluconazole-resistant Candida parapsilosis, especially in immunocompromised patients. He said, "HCW cannot decolonize patients, so we focus on appropriate treatment. If Candida causes invasive infection, ie candidemia or organ involvement, treatment should start based on a microscopic result. It must be with echinocandins to have the highest likelihood to hit the yeast hard and early. As soon as susceptibility testing results become available, they need to be reviewed versus the chosen treatment." He added, "We actually regard all patients with candidemia or invasive candidiasis as immunocompromised."

To minimize confusion due to recent taxonomic revisions of Candida species, Cornely emphasized the need for microbiology labs to report both the old and new names for Candida species. He stated, "There is only one way: we need reports from the microbiology lab that carry both names – old and new. For the majority of physicians, Candida infection is a rare disease, so a period of such reporting needs to be very long, five years minimum."

When managing invasive and mucocutaneous candidiasis in patients with underlying conditions, such as diabetes or those on immunosuppressive therapies, Cornely said, "A key consideration is the duration of therapy, immunosuppression means more treatment days. Another consideration is drug-drug interactions as many of the patients in these groups will be on multiple medications."

Regarding antifungal resistance, Cornely noted that it is increasing rapidly. He explained, "Resistance is on the rise, and it gains speed. Just a few years ago, we knew azole-resistant Candida parapsilosis only from literature; now we all see them frequently. Candida auris comes with resistance towards azoles, and some clades towards echinocandins. Pan-resistance has been found, too. Our treatment options are rapidly narrowing; we need new drugs, eg, ibrexafungerp and fosmanogepix for systemic infection."

Cornely emphasized the critical need for reliable assays to trigger treatment, stating, "We lack reliable assays to trigger treatment, fever is too unspecific, and a positive blood culture appears to occur later in the development of invasive disease." He also advocated for more research into outbreaks, "We need to intensely study outbreaks, which are often overlooked, as they may involve more than one hospital. Infection control measures can help avoid transmissions and end outbreaks; however, they were not studied to the extent necessary. We transfer evidence from bacterial infections, which is not appropriate." He finished, "Overall, there was almost no public funding available over the last 25 years. That led to a lack of research that we are now facing."

Reference

Cornely OA, Sprute R, Bassetti M, et. Al. Global guideline for the diagnosis and management of candidiasis: an initiative of the ECMM in cooperation with ISHAM and ASM. Lancet Infect Dis. 2025 Feb 13:S1473-3099(24)00749-7. doi: 10.1016/S1473-3099(24)00749-7. Epub ahead of print. PMID: 39956121