In a test of drug resistance, isolates of Candida parapsilosis were cultured in the center of a plate with fluconazole, a widely used antifungal. The fungus is considered resistant when it surpasses 8 milligrams per liter on the scale in the center. In this sample, the level exceeded 256 mg/L. Credit: FAPESP
Key Points:
- Researchers have reported the largest outbreak of COVID-associated Candida parapsilosis to date in Brazil.
- 90% of people infected by the fungus had strains resistant to the standard antifungal treatment.
- The team says the excessive use of antifungals in treating high-risk patients with long hospital stays played a part in the resistance.
Researchers in Brazil have reported a large post-pandemic outbreak of drug-resistant fungus they say is due to excessive use of antifungals in the treatment of high-risk patients with long hospital stays.
Candida parapsilosis is an emerging major human pathogen that has dramatically increased in significance and prevalence over the past two decades, such that C. parapsilosis is now one of the leading causes of invasive candidal disease.
The Brazilian outbreak described in Emerging Microbes and Infections occurred in 2020-21 in an ICU at a tertiary referral hospital in Salvador, Bahia state, during one of the peaks of the COVID-19 pandemic.
The researchers analyzed 60 isolates cultured from 57 patients who had developed C. parapsilosis candidemia in the hospital’s COVID-19 ICU. Genetic typing showed that 51 (85%) of the fluconazole-resistant isolates belonged to the same cluster, whereas the susceptible isolates each represented a distinct lineage. Part of them were also echinocandin-tolerant. Echinocandins are used against fluconazole-resistant strains of Candida.
“Ninety percent of those infected by this species of Candida had strains resistant to or tolerant of fluconazole and echinocandins, the two main classes of antifungals used to treat invasive candidiasis. Almost 60% of these patients died,” said Arnaldo Colombo, a professor at the Federal University of São Paulo’s Medical School (EPM-UNIFESP) and principal investigator for the study.
The study showed that mutations in the gene ERG11, normally considered an indicator of resistance to the class of antifungals that includes fluconazole, were present in only 35.8% of the samples. On the other hand, all resistant samples had a mutation in TAC1, which increased expression of CDR1, a gene responsible for efflux pumps, a resistance mechanism whereby resistant fungal strains acquire the ability to pump the drug out of their cells, reducing its concentration and therapeutic potential.
When this genetic mutation emerged in strains of C. parapsilosis that were originally sensitive to fluconazole, doses of the medication had to be increased eightfold in order to start inhibiting their growth. Other mutations were found in the gene FKS1, in a region where alterations of the kind are uncommon.
The researchers say the strain probably became drug-resistant due to indiscriminate use of antifungals when treating high-risk patients with long hospital stays. The practice is common in patients with severe disease who remain unstable.
“We need to establish decision-making algorithms and biomarkers so as to use antibiotics and antifungals sparingly and with the right doses and timing. That would avoid the emergence of resistant strains,” said Colombo, who is working with ANVISA, the Brazilian health surveillance authority, on protocols for treatment of fungal infections by the SUS, the national health service.
Information provided by FAPESP.