Introduction
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. Invasive mycoses can be caused by well-known species, as well as emerging pathogens, including those that are resistant to clinically available antifungals. 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.
Candidia Infections and Candida auris
Candida species are common causes of invasive infections in patients with healthcare exposure, including bloodstream infections, which are associated with substantial morbidity and mortality. Genomically, C. auris has been separated into 5 geographic clades, including: Clade I (South Asian clade), Clade II (East Asian clade), Clade III (African clade), Clade IV (South American clade), and Clade V (Iranian clade).
The high number of SNPs between the clades and the low number within each clade suggests simultaneous emergence in multiple locations rather than a clonal source. Interestingly, there appear to be clade-specific antifungal resistance patterns with the majority of isolates in Clades I and III being fluconazole resistant, while those in Clade II are susceptible to antifungals.
Unfortunately, there are now several reports of C. auris co-infections in critically ill patients with COVID-19. In one intensive care unit (ICU) setting in New Delhi, India, between April and July 2020, candidemia was diagnosed in 15 of 596 (2.5%) patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, of which 10 were due to C. auris.
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, although dissemination to other organs can occur. They are also now increasingly recognized as important causes of mycoses in critically ill patients that traditionally have not been considered at high risk, including those with acute chronic obstructive pulmonary disease. This is important as several cryptic species have reduced susceptibility to different antifungals, and many have been associated with invasive disease in both humans and animals.
Although an association between severe influenza and invasive pulmonary aspergillosis was described decades ago, we are now gaining a better understanding of influenza associated pulmonary aspergillosis (IAPA). Virus-induced anatomical and/or immunological changes are likely involved in the development of IAPA, and invasive Aspergillus tracheobronchitis (IATB) is an important manifestation of invasive aspergillosis in those with severe viral pneumonia. Invasive pulmonary aspergillosis has also recently been reported with COVID-19 disease (termed COVID-19–associated pulmonary aspergillosis, or CAPA). Studies have reported incidence rates of CAPA of between 1% to 33% in intubated patients, and overall mortality rates ranged from 44% to 74%.
Mucormycosis and COVID-19
Invasive pulmonary aspergillosis has also recently been reported with COVID-19 disease (termed COVID-19–associated pulmonary aspergillosis, or CAPA). Studies have reported incidence rates of CAPA of between 1% to 33% in intubated patients (44–47), and overall mortality rates ranged from 44% to 74%. Similar to invasive aspergillosis, 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, including the use of corticosteroids, and those suffering from major burns or through traumatic inoculation.
Even with appropriate treatment, mucormycosis is often associated with substantial morbidity and mortality. Recently, there have 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).
Another fungal infection that may be caused by several newly described species is that of sporotrichosis.
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. In addition, consideration should also be given to the emergency of fungal co-infections with other microbes, including those caused by respiratory viruses, such as influenza and SARS-CoV-2. 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
