Tuesday, April 16, 2024

CANDIDA AURIS / FUNGEMIA

Coquilla, D. September 2023

Introduction or background for CANDIDA AURIS / FUNGEMIA:

Candida auris is an emerging multidrug-resistant yeast that was first identified as a new species in 2009 (Kathuria et al., 2015). It has become a significant nosocomial pathogen, causing a wide range of infections, including fungemia and deep-seated infections, particularly in intensive care settings (Briano et al., 2022). C. auris is often misidentified as other Candida species, such as C. haemulonii, Candida famata, and Rhodotorula glutinis (Kathuria et al., 2015). Its global distribution remains unclear due to misidentification by current commercial diagnostic methods (Chatterjee et al., 2015).

Problem Statement:

The emergence of multidrug-resistant Candida auris poses a significant challenge for healthcare providers. This pathogen is resistant to multiple antifungal agents, including fluconazole, amphotericin B, and echinocandins (Ong et al., 2019; Arikan-Akdagli et al., 2018). The high mortality rate associated with C. auris infections further highlights the urgent need for effective treatment options (Briano et al., 2022). Additionally, the misidentification of C. auris as other Candida species can lead to delayed diagnosis and inappropriate treatment (Kathuria et al., 2015; Chatterjee et al., 2015).

Significance:

Solving the problem of Candida auris infections is crucial for several reasons. Firstly, C. auris has the potential to cause severe infections, especially in vulnerable populations such as critically ill patients and solid organ transplant recipients (Briano et al., 2022; Vu et al., 2022). Secondly, the global spread of C. auris and its multidrug resistance pose a threat to public health (Chen et al., 2020; Zhu et al., 2020). Lastly, the misidentification of C. auris highlights the need for accurate diagnostic methods to ensure appropriate treatment and infection control measures (Kathuria et al., 2015; Chatterjee et al., 2015; Ong et al., 2019).

Objectives or Aims:

The objectives of research on Candida auris include:

  1. Understanding the target proteins of C. auris and their role in the pathogenesis of the disease.
  2. Investigating the mechanism of action of C. auris and its resistance to antifungal agents.
  3. Identifying antibodies that can target the proteins of C. auris and potentially be used for treatment.
  4. Exploring new methods, compounds, or molecules that could serve as potential cures for C. auris and understanding their mechanisms of action.

Existing Competing Drugs and Newly Discovered Compound Candidates:

There are currently limited treatment options for Candida auris infections due to its multidrug resistance (Arikan-Akdagli et al., 2018). Existing antifungal drugs, such as fluconazole, amphotericin B, and echinocandins, may have variable efficacy against C. auris (Ong et al., 2019). However, new compounds with antifungal activity against multidrug-resistant C. auris have been identified (Wall et al., 2019). These compounds, discovered through the Medicines for Malaria Venture’s Pathogen Box, offer potential alternatives for treating C. auris infections (Wall et al., 2019).

Challenges and Overcoming Them with FDA Regulatory Experts:

There are several challenges in addressing Candida auris infections. These include the multidrug resistance of C. auris, the misidentification of the pathogen, and the need for accurate diagnostic methods (Kathuria et al., 2015; Chatterjee et al., 2015; Ong et al., 2019). Additionally, the development of new drugs or compounds requires rigorous testing and regulatory approval. Overcoming these challenges would require collaboration with FDA regulatory experts to ensure the safety and efficacy of potential treatments. This collaboration would involve conducting preclinical and clinical trials, obtaining regulatory approvals, and implementing appropriate infection control measures.

References:
Arikan-Akdagli, S., Ghannoum, M., & Meis, J. (2018). Antifungal resistance: specific focus on multidrug resistance in candida auris and secondary azole resistance in aspergillus fumigatus. Journal of Fungi, 4(4), 129. https://doi.org/10.3390/jof4040129
Briano, F., Magnasco, L., Sepulcri, C., Dettori, S., Menzaghi, B., Mikulska, M., … & Bassetti, M. (2022). Candida auris candidemia in critically ill, colonized patients: cumulative incidence and risk factors. Infectious Diseases and Therapy, 11(3), 1149-1160. https://doi.org/10.1007/s40121-022-00625-9
Chatterjee, S., Alampalli, S., Nageshan, R., Chettiar, S., & Tatu, U. (2015). Draft genome of a commonly misdiagnosed multidrug resistant pathogen candida auris. BMC Genomics, 16(1). https://doi.org/10.1186/s12864-015-1863-z
Chen, J., Tian, S., Han, X., Chu, Y., Wang, Q., Zhou, B., … & Shang, H. (2020). Is the superbug fungus really so scary? a systematic review and meta-analysis of global epidemiology and mortality of candida auris. BMC Infectious Diseases, 20(1). https://doi.org/10.1186/s12879-020-05543-0
Kathuria, S., Singh, P., Sharma, C., Prakash, A., Masih, A., Kumar, A., … & Chowdhary, A. (2015). Multidrug-resistant candida auris misidentified as candida haemulonii: characterization by matrix-assisted laser desorption ionization–time of flight mass spectrometry and dna sequencing and its antifungal susceptibility profile variability by vitek 2, clsi broth microdilution, and etest method. Journal of Clinical Microbiology, 53(6), 1823-1830. https://doi.org/10.1128/jcm.00367-15
Mohammad, H., Eldesouky, H., Hazbun, T., Mayhoub, A., & Seleem, M. (2019). Identification of a phenylthiazole small molecule with dual antifungal and antibiofilm activity against candida albicans and candida auris. Scientific Reports, 9(1). https://doi.org/10.1038/s41598-019-55379-1
Ong, C., Chen, S., Clark, J., Halliday, C., Kidd, S., Marriott, D., … & Heath, C. (2019). Diagnosis, management and prevention ofcandida aurisin hospitals: position statement of the australasian society for infectious diseases. Internal Medicine Journal, 49(10), 1229-1243. https://doi.org/10.1111/imj.14612
Vu, C., Jimenez, A., Anjan, S., & Rojas, P. (2022). Challenges and opportunities in stewardship among solid organ transplant recipients with candida auris bloodstream infections. Transplant Infectious Disease, 24(5). https://doi.org/10.1111/tid.13919
Wall, G., Herrera, N., & Lopez-Ribot, J. (2019). Repositionable compounds with antifungal activity against multidrug resistant candida auris identified in the medicines for malaria venture’s pathogen box. Journal of Fungi, 5(4), 92. https://doi.org/10.3390/jof5040092
Zhu, Y., O’Brien, B., Leach, L., Clarke, A., Bates, M., Adams, E., … & Lutterloh, E. (2020). Laboratory analysis of an outbreak of candida auris in new york from 2016 to 2018: impact and lessons learned. Journal of Clinical Microbiology, 58(4). https://doi.org/10.1128/jcm.01503-19

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