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Post-epidemic drug-resistant fungus epidemic in Brazil due to misuse of drugs and full of intensive care units

A group of researchers in Brazil has reported the largest outbreak of COVID-related candidemia to date, caused by the same drug-resistant strain of Candida parapsilosis, a fungus that invades the bloodstream and can cause death. The outbreak occurred in an intensive care unit (ICU) at a tertiary referral hospital in Salvador, Bahia state, at the height of the COVID-19 pandemic in 2020-21.

in an article published In the journal Emerging Microbes and Infections, researchers warn of the possibility of the emergence of other drug-resistant strains in the future and highlight the importance of practices that help prevent fungal infections in hospitals.

“We conducted a study in which we analyzed blood samples from patients with severe COVID-19 in hospital and found that 90% of those infected with this Candida strain had strains resistant or tolerant to the two main classes of antifungals, fluconazole and echinocandins, which are used to treat invasive candidiasis. 60 percent of them died,” he said. arnaldo colomboD., a professor at the Federal University of São Paulo School of Medicine (EPM-UNIFESP) and principal investigator of the study. Supported by FAPESP.

Researchers analyzed 60 isolates cultured from 57 patients who developed C. parapsilosis candidemia in the hospital’s COVID-19 intensive care unit. Genetic typing showed that 51 (85%) of the fluconazole resistant isolates belonged to the same cluster (has the same common ancestor), each of the susceptible isolates representing a separate lineage. Some of them were also echinocandin tolerant. Echinocandins are used against fluconazole-resistant strains of Candida.

Drug resistance can be defined as the development of the ability to multiply by a microorganism, usually even in the presence of a drug that kills it. When an antimicrobial reduces but does not inhibit proliferation, the microorganism is said to be tolerant to that drug.

“The circulation of the drug-resistant strain was likely facilitated by a healthcare worker failing to perform proper hand hygiene and contaminated vascular catheters used to administer drugs and other infusions directly into the bloodstream. This can happen when ICUs are overcrowded and staff are overworked,” he said. João Nobrega de Almeida Juniorco-author of the study.

Almeida Júnior is a researcher at FM-USP’s general and teaching hospital and Supported by FAPESP. Part of the research scholarship Supporting an internship at the Hackensack Meridian Health Center for Discovery and Innovation in the United States.

pandemic conditions

The strain also became drug resistant, possibly due to the indiscriminate use of antifungals in the treatment of high-risk patients with extended hospital stays. The practice is common in patients with severe disease who remain unstable.

“Testing to detect microorganisms takes time, and in emergencies doctors can use antibiotics and antifungals that empirically target the most likely infectious agents. Ideally, treatment for sepsis. [generalized infection] «It should require targeting several different microorganisms, but implementation must be rationalized to avoid the development of resistance, toxicity and additional costs,» said Colombo, a researcher and infectious disease specialist at São Paulo Hospital, which is also UNIFESP’s teaching hospital.

Most health centers in Brazil lack the necessary tools to perform susceptibility tests to antifungals, hindering the early recognition of drug-resistant strains. This problem facilitates the spread of fungal infections in the healthcare system. Similarly, if an agent is not characterized before an infection is treated, an ineffective drug may be given to the patient. In this context, the researchers stressed the importance of accurate diagnosis before antifungals are administered and the need for extensive molecular testing to characterize resistant agents.

The study showed that mutations in the ERG11 gene, normally considered an indicator of resistance to the fluconazole-containing class of antifungals, were present in only 35.8% of the samples. On the other hand, all resistant samples had a mutation in TAC1; this increased expression of CDR1, a gene responsible for efflux pumps; this is a mechanism of resistance where resistant fungal strains gain the ability to pump the drug out of their cells, reducing its concentration and therapeutic potential.

When this genetic mutation occurred in C. parapsilosis strains that were initially susceptible to fluconazole, drug doses had to be increased eightfold to begin to inhibit their growth. Other mutations were found in the FKS1 gene in a region where such changes are rare.

“They are drug tolerant. Killing them requires higher doses. This means that we may soon find strains resistant to this class of drugs currently prescribed for fluconazole-resistant fungi,” warned Almeida Júnior.

Suggestions

In light of their analysis of this epidemic, the researchers stress the importance of testing for fungal drug resistance in medical centers and recommend using liposomal amphotericin B to fight drug-resistant Candida, but it can have side effects and cost more than usual. fluconazole or echinocandins.

“We need to create decision-making algorithms and biomarkers to use antibiotics and antifungals sparingly, with the right dose and timing. This will prevent the emergence of resistant strains,” he said.

He also added that indiscriminate use of antibiotics is a risk factor for fungal infection. They kill intestinal microorganisms and make the intestinal walls more permeable, allowing Candida fungi, which live in the human intestine but do not cause disease under normal conditions, to pass into the bloodstream.

Systemic Candida infections occur primarily in the hospital setting where there are immunocompromised patients and where invasive procedures such as hemodialysis, mechanical ventilation and intravenous drug administration can introduce Candida into the bloodstream.

54% of the patients in the study sample were using a catheter when the infection was diagnosed. The overall 30-day mortality rate was 59.6%.

About the São Paulo Research Foundation (FAPESP)

The São Paulo Research Foundation (FAPESP) is a public institution with a mission to support scientific research in all areas of knowledge by providing fellowships, fellowships and grants to researchers affiliated with higher education and research institutions in the State of São Paulo, Brazil. FAPESP is aware that the best research can only be done by working with the best international researchers. For this reason, funding agencies in other countries recognized for the quality of their research have partnered with higher education, private companies and research organizations, and encourage scientists funded by their grants to further develop their international collaborations. Learn more about FAPESP at www.fapesp.br/en and visit the FAPESP news agency at www.agencia.fapesp.br/en to stay up to date with the latest scientific developments that FAPESP has helped to achieve through its many programs, awards and research centres. you can visit. You can also subscribe to the FAPESP news agency at https://agencia.fapesp.br/subscribe.

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