Multidrug-resistant strain of K. pneumoniae detected in Northeastern Brazil

A strain of the bacterium Klebsiella pneumoniae isolated from an 86-year-old woman with a urinary tract infection who was hospitalized in northeastern Brazil in 2022 was found to be resistant to all available antibiotics. The patient died 24 hours after admission to the hospital.

A group of researchers sequenced the bacterium’s genome and compared it to a database of 48 similar sequences. Alarmingly, the results showed that the strain in question had previously been discovered in the United States, was already circulating in Brazil and could potentially spread around the world.

The study is published in The Lancet bug.

“The bacterium is so versatile that it adapts to changes in treatment, easily acquiring resistance mechanisms that are not targeted by existing drugs, alone or in combination. The bacterium could become endemic to healthcare facilities around the world,” says Nilton Lincopan, the last author of the article. a professor at the Biomedical Sciences Institute (ICB-USP) of the University of São Paulo in Brazil.

Lincopan manages One Health Brazilian Resistance (OneBR), a database of epidemiological, phenotypic and genomic data on bacteria classified as “critical priority pathogens” by the World Health Organization (WHO).

This classification includes bacteria for which few therapeutic options are available, which merit containment measures to prevent spread, and which should be prioritized for research and development of new antimicrobials.

OneBR’s database currently contains 700 genomes of human and animal pathogens.

Health authorities are obliged to inform the local epidemiological surveillance authority when such multi-drug resistant strains are detected. The patient should be isolated and all healthcare workers involved should take extra precautions to prevent transmission of the pathogen to other patients.

“As an opportunistic pathogen, the bacterium may not cause disease in patients with normal immunity, but in people with low immunity it can cause serious infections. In the hospital environment, patients may be in intensive care units [ICUs] or being treated for other illnesses may develop a secondary infection, such as pneumonia. Because there is no treatment available and the immune system is weakened, they often die,” Lincopan said.

Favored by the pandemic

The authors note that a rapid increase in pan-beta-lactam-resistant K. pneumoniae co-producing carbapenemases was observed throughout Latin America and the Caribbean during the COVID-19 pandemic. Carbapenemases are enzymes that hydrolyze most antimicrobial compounds, making them ineffective. Beta-lactams are the most commonly used class of antibiotics.

The spread of these bacteria was reported to the Pan American Health Organization (PAHO) and WHO, which issued an epidemiological alert.

A global genomic analysis published Recently, a group led by Fábio Sellera, a professor at the Metropolitan University of Santos (UNIMES) in Brazil, also reported a rapid growth of multidrug-resistant bacteria, highlighting that the high prevalence of K. pneumoniae strains indicates a new resistance trend and a serious threat to public health.

An antibiotic was developed that combines a third-generation cephalosporin, ceftazidime, with a new beta-lactamase inhibitor, avibactam. approved by the US Food and Drug Administration (FDA) in 2015 and is indicated for the treatment of K. pneumoniae carbapenemase (KPC)-producing bacteria.

Ceftazidime/avibactam was approved in 2018 by ANVISA, the Brazilian equivalent of the FDA, given the high number of reported KPC infections.

“The hospitalization of people with COVID-19 associated with secondary infections by this type of bacteria likely led to a global increase in the use of ceftazidime/avibactam, which promoted the emergence of strains resistant to this new antibiotic,” Lincopan said.

The standard procedure for patients admitted to hospital with suspected bacterial infections would consist of collecting clinical material to confirm the diagnosis and testing for susceptibility to the various antimicrobial agents available.

“KPC-producing strains treated with ceftazidime/avibactam likely evolved rapidly and acquired resistance to this latest therapeutic option. We now have carbapenemase co-producing strains that do not respond to treatment with beta-lactams,” he said.

In addition to the need for permanent monitoring of the disease-causing bacteria found in hospitals, the researchers also emphasize the importance of rational prescribing of antibiotics. The message for patients is that when antibiotics are prescribed, they should adhere to the full course of treatment, even if they feel well after two or three days. This will also prevent the emergence of more resistant strains.

The paper’s first author was Felipe Vásquez Ponce, a Ph.D. candidate at ICB-USP. The study was also supported by Johana Becerra, a researcher at ICB-USP and member of the OneBR team.