COVID-19 Creates Conditions for Emergence of Invasive “Superfungus” in Brazil

Fluorescence microscopy image illustrating the morphology of C. auris. Credit: João Nóbrega Almeida Junior/UNIFESP

Fully occupied intensive care units (ICUs). Physically and mentally exhausted health professionals. Chaotically overcrowded hospitals. These and similar problems caused by the COVID-19 pandemic in Brazil have created ideal conditions for the emergence of Candida auris, a microorganism that some are calling a “super fungus” due to the rate at which it has developed drug resistance.

The first two cases were confirmed in December 2020 at a hospital in Salvador (state of Bahia, Northeast Brazil) and are described in the Journal of Fungi by a group of researchers led by Arnaldo Colombo, head of the Special Mycology Laboratory at the Federal University of Sao Paulo (UNIFESP). The study was supported by FAPESP.

“Since then, nine other C. auris patients have been diagnosed at the same hospital, some colonized” [with the fungus in their organism but not doing harm] and others infected,” Colombo told Agência FAPESP. “No other cases have been reported in Brazil, but there is cause for concern. We follow the evolutionary features of C. auris isolates from patients in hospital in Salvador, and we have already found samples with reduced susceptibility to fluconazole and echinocandins. The latter belong to the most important class of drugs used to treat invasive candidiasis.”

With the exception of C. auris, fungi of the genus Candida are part of the human gut flora and only cause problems when there are imbalances in the organism, Colombo explained. These include infections such as vaginal yeast infection and thrush (oral candidiasis), often caused by C. albicans.

In some cases, however, the fungus enters the bloodstream and causes a systemic infection known as candidaemia, the most common form of invasive candidiasis, similar to bacterial sepsis. Invasion of the bloodstream and the aggravated immune system response to the pathogen can cause damage to various organs and even lead to death. According to scientific evidence, mortality among candidemia patients infected with C. auris can be up to 60%.

“The species quickly becomes resistant to multiple drugs and is not very sensitive to the disinfectants used by hospitals and clinics,” Colombo said. “As a result, it can persist in hospitals, colonizing health workers and eventually infecting patients with severe COVID-19 and other critical long-stay patients.”

Several factors make patients infected with SARS-CoV-2 ideal targets for C. auris, including long hospital stays, urinary and central venous catheters (allowing for bloodstream invasion), and steroids and antibiotics (which disrupt the gut flora).

“The virus can damage the intestinal mucosa of severe COVID-19 patients [facilitating invasion of the bloodstream by pathogens] so that the patient becomes vulnerable to candidemia,” Colombo said.

Several countries have reported the emergence of C. auris during the COVID-19 pandemic, he added, making the need to fight nosocomial infections across Brazil even more urgent. Rational use of antimicrobial drugs in ICUs is equally important. Since the start of the pandemic, azithromycin and other antibiotics have been prescribed more widely, usually without real justification.

Monitoring

C. auris was first isolated in Japan in 2009, but the scientific community paid little attention to it until several years later, when outbreaks of candidemia caused by the super fungus occurred in Asia and Europe. In 2016, a UNIFESP group article in the Journal of Infection reported the species’ arrival in the Americas via Venezuela. It was soon discovered in Colombia, Panama and Chile.

“In 2017, we participated in a task force convened by the Ministry of Health and ANVISA [Brazil’s health surveillance authority] and wrote a technical standard [Risk Notice 01/2017] health authorities are warning that precautions must be taken to control the possible arrival of C. auris in Brazil, which was only confirmed at the end of last year,” Colombo said.

Since then, the UNIFESP team has monitored the emergence of new fungal pathogens in bloodstream infections, documented by medical centers across Brazil, without detecting C. auris to date.

Five clades or genera of C. auris have been described in the world so far. According to Colombo, the clade isolated in Salvador is more similar to the Asian original than the variant discovered in Venezuela and other South American countries, indicating a second independent arrival of the super fungus on the continent.

“Alternatively, there may be a local environmental source, as none of the Brazilian patients infected with the fungus has traveled abroad or infected family members,” Colombo said.

Every month since December, the researchers have been receiving samples of the clade isolated at the hospital in Salvador to test its susceptibility to antifungal drugs in their lab.

“In these tests, we expose the cultured microorganism to progressive concentrations of antifungal agents to determine the lowest dose that can inactivate it. For example, in the case of C. auris present in samples recently isolated in Salvador, the dose must be four to five times greater than the dose used to inactivate the isolate grown in December 2020,” said Colombo.

In collaboration with Dutch colleagues, the UNIFESP group is conducting a genetic sequencing study to see whether the gene that confers resistance to C. auris has mutated over time.

“The mechanism that allows the species to develop drug resistance is not enzymatic degradation, as in so many bacteria that are resistant to antibiotics,” Colombo said. “The fungus develops structural modifications in the proteins to which the drug binds to inhibit cell wall synthesis.” [glucan synthase in the case of echinocandins], which is the key to its survival. We see this phenomenon happening here in Brazil.”

In addition to redoubled care with hygiene, surveillance efforts to detect suspected pathogens need to be stepped up, he added. Confirming the presence of C. auris in a sample is not a trivial task, requiring specific equipment. The most commonly used technique is matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry, quite common in microbiology labs, but not always available in hospitals in Brazil.

“If the analysis is performed using conventional automated methods, C. auris can be confused with other species, such as C. haemulonii or C. lusitaniae. Ideally, any strain of Candida showing drug resistance should be sent to a reference lab for analysis,” Colombo said.

Reference: “Emergence of Candida auris in Brazil in a COVID-19 Intensive Care Unit” by João N. de Almeida, Jr., Elaine C. Francisco, Ferry Hagen, Igor B. Brandão, Felicidade M. Pereira, Pedro H. Presta Dias, Magda M. de Miranda Costa, Regiane T. de Souza Jordão, Theun de Groot and Arnaldo L. Colombo, March 17, 2021, Journal of Fungi.
DOI: 10.3390 / jof7030220