Cristina Azevedo (Fiocruz News Agency)
A project resulting from a partnership between the Ministry of Health, Fiocruz, Lacen-PR, and the Federal University of São Paulo (Unifesp) was one of those selected by the U.S. Centers for Disease Control and Prevention (CDC) for funding, as part of the creation of two global networks aimed at fighting antimicrobial resistance. With Ana Paula Assef, head of the Hospital Infection Research Laboratory (LAPIH) at the Oswaldo Cruz Institute (IOC/Fiocruz), as the principal investigator, the Strengthening Brazilian Surveillance System for Antimicrobial Resistance program aims to reinforce the detection of multidrug-resistant bacteria and fungi (Candida) in hospitals, train professionals, and enable more accurate and rapid responses from health professionals.
"Bacteria are increasingly resistant to antibiotics and we need to see what is really happening inside Brazilian hospitals," says Ana Paula. "This project goes from improving diagnosis in hospitals to a deeper knowledge of bacteria with the sequencing of their total genome."
With annual funding of about US$800,000 from the CDC, the project will be evaluated every year and may extend until 2026. The Ministry of Health will also contribute with inputs and logistical support. The initiative will act on two fronts: one for antimicrobial resistance to bacteria and another for fungi (Candida).
The project builds on an earlier Ministry of Health initiative, BR-GLASS, which started the pilot project in Paraná. Five sentinel hospitals in the Southern Region monitor cases and send data to GLASS, a worldwide surveillance platform. With the new project, these five hospitals will be joined by ten more distributed throughout the five regions of the country. "The idea is to add more hospitals each year in order to cover the whole country," says Ana Paula.
Application for antimicrobial prescriptions
The samples of multiresistant bacteria and fungi from chosen patients are sent to the Central Public Health Laboratories (Lacen), then to the five regional reference Lacen, and finally to LAPIH and Lacen Paraná, which coordinate the project. The data will be posted on BR-GLASS so that real-time monitoring can be done, with alerts sent to hospitals when outbreaks are detected.
Hospital laboratories will receive rapid tests to detect carbapenemases, enzymes that make bacteria resistant to most antibiotics. "It is critical to know if these bacteria that are causing the infections produce carbapenemases, if the antibiotic resistance is because of these enzymes, and what the enzyme is. This test allows us to detect five different carbapenemases," said the researcher.
From the test, the doctor can see which antibiotic works or not, avoiding what Ana Paula calls "selective pressure", which leads bacteria to increase their resistance. The results will also allow the spread of the bacteria in the hospital to be controlled.
The medical prescription will have a further aid: a cell phone application - the Smart CDSS - in which the doctor describes the patient's data and the infection type. Based on the resistance profile of that location, the program previously developed by Lacen-PR and PUC-PR, with resources from the Bill & Melinda Gates Foundation and the Ministry of Health, will indicate the appropriate medication. "We have developed an algorithm, which uses the hospital's own data to calculate which drug is best to prescribe for that specific patient. It is the empirical prescription, based on local and updated evidence," says Marcelo Pillonetto, a researcher at Lacen-PR and PUC-PR, who idealized the application project and coordinates the project's laboratory activities with the CDC.
A Brazilian database
Some of the selected samples from the sentinel hospitals will go to the regional Lacen sites for further molecular testing to detect resistance genes. Then the total genome of these samples will be sequenced in the reference laboratories: LAPIH and Lacen Paraná, which are coordinating the project. This will provide a deeper understanding of which bacteria are multidrug-resistant in the country, whether there are any specific clones and the resistance mechanisms that are spreading, as well as to detect new resistance genes.
"We always follow the American or the European manual, based on the profile of the bacteria that they test. We need to know what happens in Brazil to see if those results fit. We want to establish our database and our manual," Ana Paula explained.
The same process will be employed with respect to fungi. Some laboratories cannot detect certain Candida spp. that are important in hospital-acquired infections. The project should strengthen Candida auris detection, for example, which is extremely resistant to antifungal drugs.
At the pandemic beginning, the WHO warned of the increased antimicrobial resistance possibility - also considered a pandemic. And indeed, a Fiocruz study showed the increase in hospital infection last year, when it went from nearly 1,000 positive samples studied in 2019 to approximately 2,000 in 2020.
"Patients stay in the hospital for a long time, they get intubated, they use a catheter... this is all a full plate for the bacteria that are in the hospital to cause an infection. The longer you are hospitalized, the greater the chance of acquiring a hospital infection and using antibiotics. This will make selective pressure within the hospital. That's why several initiatives arose and this CDC notice," Ana Paula explained.
In addition to the funding, the CDC will monitor the projects, exchanging ideas and giving suggestions. "This partnership is very interesting, it can help improve surveillance," says Ana Paula. "The proposal is to increase each year, both the hospitals and the Lacen, so that serves entire Brazil.
Besides Ana Paula Assef, Carla Freitas and Renata Tigulini de Souza Peral (Management Committee of Laboratory Resources - CGLAB, Ministry of Health); Hayne Felipe da Silva (Fiotec); Marcelo Pillonetto (Lacen Paraná); Carlos Roberto Veiga Kiffer (LEMC-Unifesp), Arnaldo Lopes Colombo and João Nóbrega de Almeida Júnior (LEMI-Unifesp) also participate in the project.
On Tuesday (12/7), the CDC announced two new global networks and research projects, granting US$ 22 million to approximately 30 organizations around the world to fight antimicrobial resistance and other health threats: the Global Health Care Action Network and the Global Network for Laboratories and Response to Antimicrobial Resistance - in which the project in which Fiocruz participates through Fiotec.
The two networks will span more than 50 countries and create programs focused on preventing infections in health care through infection control; building laboratory capacity to detect antimicrobial-resistant organisms in health care, the community, and the environment; and developing innovative ways to detect and respond to threats such as antimicrobial resistance and Covid-19 faster.
The Global Antimicrobial Resistance Laboratory and Response Network is a global collaborative initiative led by the US CDC to enhance capabilities to detect and respond to antimicrobial-resistant threats within the One Health spectrum. This work is funded by the CDC's AR Solutions Initiative. The CDC is a United States Department of Health and Human Services (HHS) agency.