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Hospital-Acquired Yeast Pathogen Not Controlled by Antifungals; Biofilm Concern


A new study published by the CDC in February 2017 reported that, due to its ability to form biofilm, the spread and prevalence of the highly virulent, multidrug-resistant, yeast pathogen Candida auris (C. auris) in hospital environments is not likely to be controlled with standard antifungal approaches.

 

The yeast pathogen C. auris was first detected in 2009 from an ear canal infection in Japan. This species initially attracted attention because of its reduced susceptibility to azoles, a class of oral antifungal drugs for the treatment of systemic fungal infections, and amphotericin B, an antifungal medication used for serious fungal infections, combined with the lack of reliable culture-based methods for its identification.

 

More recently, C. auris has been associated globally with life-threatening invasive nosocomial diseases, such as bloodstream and wound infections. C. auris has also caused hospital outbreaks across Asia and South America. In addition, in a UK intensive care unit, candidemia, the fourth most common cause of nosocomial bloodstream infections, developed in 20% of patients colonized with C. auris. Although the mode of transmission within hospitals is unknown, C. auris may substantially contaminate rooms of colonized or infected patients.

 

In addition to its multidrug-resistance, C. auris is also noteworthy for its virulence, the severity of the disease it causes. One factor increasing its virulence is this pathogen’s ability to form biofilm, a collective of one or more types of microorganisms that can grow on many different wet surfaces.

 

Researchers sought to examine C. auris in the context of biofilm-forming capacity, investigate its susceptibility to a panel of antifungal agents and the skin disinfectant chlorhexidine, and investigate its virulence in vivo.

 

Researchers used C. albicans, the most common species of Candida yeasts that cause infection in humans, and C. glabrata, the main species of Candida yeasts that exhibits multiazole, echinocandin (a new class of antifungal drugs), and multidrug resistance, as comparators for C. auris. C. albicans displayed the greatest biofilm mass, consistent with previous findings. Compared with C. albicans, all C. auris strains formed significantly reduced biofilms, between 1.5 and 3.1 times less depending on the strain. However, these strains formed significantly greater biofilms than those formed by C. glabrata, between 2.9 and 6.0 times more depending on the strain.

 

Researchers performed antifungal susceptibility testing using fluconazole, voriconazole, caspofungin, micafungin, liposomal amphotericin B, amphotericin B, and chlorhexidine. Fluconazole was ineffective against planktonic cells, single cells that may float or swim in a liquid medium, and sessile cells, yeast cells immobilized in biofilm, whereas voriconazole displayed minimal activity against planktonic cells. Although liposomal amphotericin B was active against planktonic C. auris at 0.25–1.0 mg/L, up to 16 mg/L was required to reduce biofilm metabolic viability by 90%. Amphotericin B was more effective, requiring only 4 mg/L to kill biofilms. Micafungin was the most active echinocandin, requiring less than 0.5 mg/L to inhibit planktonic cells, compared with 2–32 mg/L for caspofungin. However, these two echinocandin antifungal agents were ineffective against biofilms, requiring more than 32 mg/L to inhibit sessile cells. Of note, chlorhexidine exhibited the greatest activity, requiring less than 0.02% to effectively inhibit planktonic and sessile cells across all strains tested.

 

Killing assays in Galleria mellonella were performed to assess the pathogenicity of each Candida species. Survival data showed a significantly lower pathogenicity by C. glabrata than the other Candida species. Although C. albicans and C. auris had similar kill kinetics in this model, infection with one particular C. auris strain achieved a 100% death rate within 48 hours, compared with a rate of about 87% with C. albicans. Moreover, the strain of C. auris that produced the greatest amount of biofilm was significantly more pathogenic than other strains of C. albicans when a smaller amount of yeast cells was administered. These data suggest that that strain of C. auris has the capacity to form biofilms with enhanced virulence capacity.

 

The researchers concluded that biofilm formation is a key driver of C. albicans pathogenicity and is associated with patient death. The researchers showed that C. auris can differentially adhere to polymeric surfaces, form biofilms, and resist antifungal agents that are active against its planktonic counterparts. Of particular interest, caspofungin was predominately inactive against C. auris biofilms; this finding was unexpected because caspofungin is normally highly effective against Candida biofilms. These features contribute not only to C. auris virulence but also to its survival in hospital environments, increasing its ability to cause outbreaks. The results of the in vivo model used in this study were in line with the researchers’ clinical experience and validated by findings in other in vivo studies, affirming that C. auris is highly virulent or more virulent than C. albicans.

 

Although unable to form biofilms equivalent to C. albicans, C. auris has a noteworthy virulence capacity that merits further exploration, particularly given the apparent heterogeneity associated with different strains. These factors, together with the innate resistance of C. auris to most antifungal agents, may explain why it is an emerging pathogen. The researchers’ findings suggest it is improbable that the spread and prevalence of C. auris can be controlled with antifungal stewardship approaches alone. Research showed that chlorhexidine is effective against C. auris planktonic and sessile communities. Thus, use of chlorhexidine can be advocated for topical control of C. auris at standard concentrations used for skin and wound cleansing and disinfection (0.05%–4.0%). Infection-prevention measures targeting C. auris biofilms in patients, on medical devices (e.g., equipment in contact with patients), and in the hospital environment will be required.

 

See the CDC Report

 

See the CDC C. auris site

 

See also Medical Law Perspectives, June 2016 Report: How Risky Is Going to the Hospital? The Dangers and Liabilities of Healthcare-Associated Infections

 

See also Medical Law Perspectives, October 2015 Report: Unclean, Unsterile, Unsafe: Risks of Injury from Unsterilized Medical Equipment

 

See also Medical Law Perspectives, January 2012 Report: Hospital-Acquired Infections: Who is Liable and Why? 

 

 

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