Clinical pearls related to emerging fungal pathogens
Candida auris. This organism has emerged simultaneously on several continents. It has pathogenicity factors typical of the genus, such as biofilm formation and production of phospholipases and proteinases, although it has greater thermal tolerance. In hospitals, it colonizes for weeks and months. In Argentina, it is resistant to multiple antifungal agents. Sensitivity is variable in different geographical regions. Most strains are resistant to fluconazole, and there is variable resistance to the other triazoles [which are not normally used to treat candidemia]. In the United States, in vitro resistance to amphotericin B is up to 30%, and resistance to echinocandins is up to 5%. New drugs such as rezafungin and ibrexafungerp are being studied. Infection control is similar to that used to control Clostridium difficile.
Fusarium. This genus affects immunocompromised patients, including transplant recipients of solid organs and hematopoietic progenitor cells and patients with neutropenia. The genus has various species, included within complexes, such as F. solani SC, F. oxysporum SC, and F. fujikuroi SC, with clinical manifestations similar to those of aspergillosis. In addition to the pulmonary and disseminated forms, there may be skin involvement attributable to dissemination from a respiratory focus or by contiguity from a focus of onychomycosis. In general, mortality is high, and responses to antifungal agents are variable. Some species are more sensitive to voriconazole or posaconazole, and others less so. All show in vitro resistance to itraconazole. In Argentina, voriconazole is usually used as initial treatment, and in special cases, liposomal amphotericin B or combinations. Fosmanogepix is being evaluated for the future.
Azole-resistant aspergillosis. This infection has shown resistance to itraconazole and third-generation azole drugs. In immunocompromised patients, mortlaity is high. Early detection is key. It is sensitive to amphotericin B and echinocandins. It is generally treated with liposomal amphotericin B. Olorofim and fosmanogepix are being studied.
Pulmonary aspergillosis associated with COVID-19. This infection is associated with high mortality among intubated patients. Signs and symptoms include fever, pleural effusion, hemoptysis, and chest pain, with infiltrates or cavitations on imaging. Determining the diagnosis is difficult. “We couldn’t perform lung biopsies, and it was difficult for us to get patients out of intensive care units for CT scans. We treated the proven cases. We treated the probable cases, and those that had a very low certainty of disease were also treated. We came across this emergency and tried to do the best we could,” said Dr. Afeltra. A digital readout lateral flow trial (Sona Aspergillus Galactomannan LFA) for the quantification of galactomannan, a cell wall component of the Aspergillus genus, proved to be a useful tool for screening and diagnosing patients with probable pulmonary aspergillosis associated with COVID-19. The incidence of invasive mycosis was around 10% among 185 seriously ill COVID-19 patients, according to an Argentine multicenter prospective study in which Dr. Afeltra participated.
Scedosporium and Lomentospora. These genera are rarer septate hyaline fungi. Scedosporium is a complex of species. One species, S. apiospermum, can colonize pediatric patients with cystic fibrosis. Lomentospora prolificans is a multiresistant fungus. It produces pulmonary compromise or disseminated infection. The response to antifungal agents is variable, with a high minimum inhibitory concentration for amphotericin B and isavuconazole. Patients are usually treated with voriconazole alone or in combination with terbinafine or micafungin. Olorofim is emerging as a promising treatment.
Dr. Afeltra has received fees from Biotoscana, Gador, Pfizer, Merck, and Sandoz.
This article was translated from the Medscape Spanish edition, a version appeared on Medscape.com.