Antifungal resistance of Candida auris contributes to treatment failure


Recent research published in journals biomedical aimed to determine the antifungal resistance of Candida auris (C. auris) Applies to all three classes of antifungal drugs commonly used to treat invasive candidiasis.

Microbial infections are caused by harmful bacteria, fungi, or viruses and affect millions of people worldwide. An increase in antimicrobial resistance (AMR) is being observed globally, threatening healthcare systems. Among AMR, antifungal resistance is mainly found in immunocompromised patients.

Research: Identification and elimination of antifungal resistance in Candida auris. Image Credit: Kateryna Kon Shutterstock

Background

Fungi thrive in warmer temperatures, and climate change has helped their growth. Scientists are particularly concerned about antifungal resistance due to the limited number of classes of antifungal drugs. Surprisingly, no new class of antifungal drugs has hit the market in over a decade.

One of the most common fungal infections is caused by: Candida yeast species. Clinicians have expressed particular concern about fungal infections caused by: C. auris Because it is resistant to antifungal drugs. This fungal pathogen is found in more than 47 countries around the world and has a mortality rate of up to 45% in patients with bloodstream infections.

C. auris Shows multidrug resistance. When a particular fungus is resistant to one or more of three or more antibiotics, it is known as multidrug resistance. In particular, in some cases C. auris It also shows pan-drug resistance, which was found to be insensitive to drugs belonging to all antibacterial classes.

It is important to note the difference between antifungal resistance and antifungal resistance. Antifungal resistance results from inherited genetic alterations that allow fungal cells to grow above the minimum inhibitory concentration (MIC) in a concentration-dependent manner. However, antifungal resistance results from phenotypic heterogeneity, a reversible phenomenon. Tolerant cells grow slowly beyond the MIC.

Understanding the mechanisms associated with resistance is essential. Candida Race. Previous studies have shown that multiple factors, such as aneuploidy, are associated with resistance. Candida Race. Hsp90-promoted azole resistance is C. aurisit is unknown whether this fungal species is resistant to non-azole antifungal drugs.

There are currently no clinical assays to identify antifungal resistance. This can be very informative in determining the efficacy of single and combination antifungal therapies.

About research

In this study, broth microdilution and disk diffusion assays were used with diskImageR to assess fungal resistance to different classes of antifungal drugs. Additionally, an analysis was performed to test whether fungal resistance could be eliminated by adjuvant antifungal therapy.

Minimum inhibitory concentration (MIC) of clinical C. auris isolates (apicture) grown in antifungal microwell plates to determine susceptibility/resistance to antifungal drugs. Mean MICs of five clinical C. auris isolates measured after 24 and 48 hours for four fungicides (fluconazole, itraconazole, posaconazole, and voriconazole) and two fungicides (amphotericin B and caspofungin). Different symbols indicate C. auris isolates with the same MIC.

each MIC C. auris Isolates were determined using a broth microdilution assay.of antifungal resistance C. auris It was analyzed against different classes of antifungal agents, including fluconazole, amphotericin B, itraconazole, anidulafungin, voriconazole micafungin, caspofungin and posaconazole.

Images of each disc diffuser were acquired at full resolution after 24 and 48 hours. Fungal resistance was quantified using supra-MIC growth from the microbroth dilution assay and growth rate (FoG) in the zone of inhibition (ZOI) from the disc diffusion assay.

The authors also analyzed the efficacy of combination therapy with an antifungal agent and an adjuvant (chloroquine) C. auris, C. parapsilosisand Isacenquia oriental.

Investigation result

Limited number of clinical C. auris The isolates were resistant to fungistatic agents such as fluconazole, voriconazole, itraconazole, and posaconazole, and bactericidal agents such as amphotericin B and caspofungin. Azole resistance is C. parapsilosis; but, I. Orientalis Maintained resistance to fluconazole.

Resistance was detected after 24 and 48 hours by FoG and recorded using diskImageR and ImageJ.This finding suggests that a specific subpopulation C. auris Insensitive to various antifungal agents.

Importantly, this resistance quantification method can be used in clinical diagnostic laboratories along with standard tests for antifungal susceptibility/resistance to develop better antifungal strategies.

Significantly fewer resistant fungal cells grew within the ZOI upon subculture than the parental population, indicating the presence of phenotypic heterogeneity rather than genetic variation.

In the future, related underlying mechanisms C. auris Tolerance should be studied. In particular, the authors observed reduced or lost tolerance in some patients. C. auris Combine and separate antifungal drugs (azoles, polyenes, echinocandins) and antimalarial drugs (chloroquine).

Conclusion

C. auris Several antifungal drugs such as caspofungin, fluconazole, posaconazole, voriconazole, itraconazole, and amphotericin B were resistant. Fungal resistance is a reversible phenomenon and can be detected at 24 and 48 hours.

This study is the first to demonstrate that combining an antifungal drug with the adjuvant chloroquine can eliminate resistance and tolerance in patients. C. aurisHowever, the findings should be validated using: in vitro and in vivo experiment.

written by

Dr. Priyom Bose

Priyom holds a Ph.D. He holds a PhD in Plant Biology and Biotechnology from the University of Madras, India. She is an active researcher and an experienced science her writer. Priyom has also co-authored several original research papers published in reputable peer-reviewed journals. She is an avid reader and amateur photographer.

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