Title : Candida auris infections are global health challenge
Abstract:
The CDC classifies C. auris as an urgent antimicrobial resistance threat, the highest level of concern due to its resistance to multiple antifungal drugs and the ease of transmission in healthcare settings. The WHO places it in the critical priority group of fungal pathogens. C. auris has five recognized clades worldwide classified as South Asian, East Asian, African, and South American. Clade V was recently discovered in Singapore and Bangladesh and has close genetic relationship to Clade IV but represents a distinct lineage. C. auris’ spread in the U.S. has been alarming, with number of clinical cases increasing markedly since its first reported cases in 2016. Since 2023, there has been well over 4,000 cases. C. auris is known for its multidrug resistance profile and can cause severe and often life-threatening infection. The fungus spreads easily in healthcare facilities and primarily affects people who are already immunocompromised or have co-morbid conditions. Worldwide, this fungal pathogen is rapidly emerging across six continents over 60 countries, with outbreaks particularly concentrated in hospitals and healthcare facilities, makes it a serious global epidemic concern. It should be noted a C. auris case was first reported in 2009 by Japanese investigators, though retrospective samples show it existed as early as 1996 in South Korea. C. auris infections present with nonspecific symptoms and vary depending on the site of infection, most often involving the bloodstream, wounds, or ears. Interestingly, in Western Europe, Spain currently has the highest number of reported cases of C. auris with nearly 2,000 cases between 2013 and 2023. Columbia has also reported more than 2,000 cases and has a high incidence of C. auris candidemia, while South Africa, India, and US (particularly NY and NJ) are experiencing significant number of cases. It seems for many countries, sustained hospital outbreaks, gaps in infection control, and robust surveillance that detects more cases are the main challenging gaps – Once established in the healthcare facilities, the fungus is extremely difficult to eradicate from their environments. Many patients are colonized without symptoms, but invasive infections can be severe risking mortality. Usually candidemia presents with fever, chills, hypotension, tachycardia, or sepsis-like symptoms often indistinguishable from other causes of sepsis. C. auris otitis presents with pain, pressure, or fullness in the ear. Other sites include urinary tract, respiratory tract, and intra-abdominal infections, though less common. The core pathophysiologic features of C. auris include its ability to colonize skin and hospital environments, resist antifungal drugs, evade immune defenses, and cause invasive bloodstream infections in vulnerable patients. The fungus has evolved having extraordinary ability to form multilayer biofilms and to resist both antifungal
2 | P a g e
drugs and hospital cleaning protocols. Fungal biofilms can block penetration of antifungal drugs, especially azoles and echinocandins. The extracellular matrix acts like a shield, trapping and neutralizing drugs before they reach fungal cells. Biofilms allow the fungal pathogen to survive for weeks on surfaces resisting standard disinfectants. This type of persistence seems to be a major reason for outbreaks that are hard to control once the fungus enters a healthcare setting. Clinical isolates show enhanced adherence due to amplification of adhesin genes such as ALS4, which increases surface colonization and biofilm capacity. In addition, a newly identified adhesin, Scf1, is critical for biofilm formation on skin and devices, highlighting potential therapeutic targets. The clinical impacts are concerning worldwide, one of the urgent concerns is that biofilm-associated resistance leads to high treatment failure rates and frequent relapses. Recent studies show about 90% of isolates are resistant to at least one antifungal drug. About 30% are resistant to two or more drug classes. Rare strains show pan-resistant patterns to azoles, echinocandins and amphotericin B. Mutations in ERG11 (azole target) and FKS1 (echinocandin target) reduce drug binding. Alterations in sterol biosynthesis pathways confer amphotericin B resistance. Mortality rates for invasive C. auris infections remain 30–60%, especially in critically ill patients. The current guidelines for management of C. auris infections emphasize echinocandins as the 1st-line therapy and mandatory reporting to public health authorities. For adults & children ≥ 2 months, anidulafungin, caspofungin, or micafungin are recommended as the initial treatment. For infants < 2 months, amphotericin B deoxycholate (1 mg/kg daily) is recommended. If echinocandin resistance is suspected or confirmed, switch to liposomal amphotericin B (5 mg/kg daily). For management of pan-resistant strains, consider investigational antifungals (e.g., fosmanogepix, ibrexafungerp) under expanded access programs.
