Emerging Fungal Infections: New Species, New Names, and Antifungal Resistance

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Introduction

Infections caused by fungi can be important causes of morbidity and mortality in certain patient populations, including those who are highly immunocompromised or critically ill. Invasive mycoses can be caused by well-known species, as well as emerging pathogens, including those that are resistant to clinically available antifungals. This review highlights emerging fungal infections, including newly described species, such as Candida auris, and those that having undergone taxonomic classification and were previously known by other names, including Blastomyces and Emergomyces species, members of the Rasamsonia argillacea species complex, Sporothrix brasiliensis, and Trichophyton indotinae.

Antifungal resistance also is highlighted in several of these emerging species, as well as in the well-known opportunistic pathogen Aspergillus fumigatus. Finally, the increased recognition and importance of fungal co-infections with respiratory pathogens, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is discussed. Examples of emerging fungal pathogens are shown in Fig.  1.

Candidia Infections and Candida auris

Candida species are common causes of invasive infections in patients with healthcare exposure. Candida species have emerged with higher rates of antifungal resistance, especially to fluconazole. One new species, Candida auris, was first isolated from the external ear canal of a patient in Japan. Genomically, C. auris has been separated into 5 geographic clades.

Each clade differs by >10 000 single nucleotide polymorphisms (SNPs). There appear to be clade-specific antifungal resistance patterns with the majority of isolates in Clades I and III being fluconazole resistant. C. auris frequently colonizes the axilla, groin, nares, respiratory tract, and urinary tract of patients. This species has also been found on numerous objects within patient rooms and can also colonize healthcare workers. Commonly used disinfectants in healthcare settings have limited activity against this organism.

In the US approximately 90% of isolates are fluconazole resistant, 30% are resistant to amphotericin B, and 5% are also resistant to the echinocandins, which are currently the drugs of choice for the treatment of invasive infections.

Aspergillosis Including Azole-Resistant Aspergillus and Co-Infections with Viral Pneumonia

Aspergillus species are important causes of invasive and chronic infections that typically involve the lungs. Highly immunocompromised patients are one of the groups recognized as being at greatest risk for invasive disease. Fumigatus may occur in 3.5% to 5% of clinical isolates. The most prevalent of the environmental exposure mechanisms of resistance are TR34/L98H and TR46/Y121F/T289A. Both acute and chronic forms of aspergillosis are most often caused by a handful of species. There are over 200 individual species within the genus Aspergillus.

Several cryptic species have reduced susceptibility to different antifungals, and many have been associated with invasive disease in both humans and animals. Invasive Aspergillus tracheobronchitis (IATB) is an important manifestation of. invasive aspergillosis in those with severe viral pneumonia. Plaques in the trachea and bronchi are observed due to epithelial erosion caused by viral replication.

Mucormycosis and COVID-19

Mucormycosis is a well-known type of fungal infection. However, the incidence of this highly aggressive and destructive invasive mycosis has increased in several countries due to increases in the numbers of patients at risk, which includes those with poorly controlled diabetes mellitus, patients with profound neutropenia or other forms of immunosuppression. Even with appropriate treatment, mucormycosis is often associated with substantial morbidity and mortality. Recently, there have Emerging Fungal Infections: New Species, also been numerous reports of mucormycosis in patients with SARS-Cov-2 infection, termed COVID-19–associated mucormycosis (CAM).

CAM has been documented in several countries, and many of these infections were identified during the second COVID-19 surge that occurred in India in the winter and spring of 2021, with many of these patients suffering from rhino-orbital cerebral mycosis.

Changes in Fungal Taxonomy and Recognition of Mycoses Due to New Species

There are many examples of fungi that are newly recognized as distinct species due to changes in fungal taxonomy brought on by phylogenetic analysis. Several of these are also now considered emerging pathogens, either due to increased awareness secondary to advances in diagnostic assays or concern due to antifungal resistance (Table  1).

Conclusion

Over the last several years, there have been numerous reports of emerging fungal infections, many of which may be difficult to diagnose and treat and are associated with substantial morbidity and mortality in at-risk patient populations. Clinicians and clinical microbiology laboratories should remain vigilant toward these emerging fungal infections as well as the development of antifungal resistance, which can occur in both well-known pathogens and newly described fungal species. Some of these emerging fungal infections and those that cause co-infections with respiratory viruses have been associated with corticosteroid use.

Source:   Nathan P Wiederhold, Emerging Fungal Infections: New Species, New Names, and Antifungal Resistance, Clinical Chemistry, Volume 68, Issue 1, January 2022, Pages 83–90, https://doi.org/10.1093/clinchem/hvab217