Researchers are working to increase bacterial resistance to carbapenem antibiotics

Enterobacteriaceae, such as Escherichia coli and Klebsiella pneumoniae, are terrifying hospital bacteria that can cause serious intestinal and urinary tract infections. The risk of infection by these pathogens is due to their increasing resistance worldwide and resistance to the carbapenem, a group of antibiotics that effectively make up an important reserve of emergencies. Is growing. The new combination of the two antibacterial substances was seen as a sign of hope for treatment, which was made by recent studies at the University of Giessen (JLU) and the German Center for Infection Research (DZIF). It was crushed. Even before the substance was used in Germany, scientists were able to find bacteria that this new combination could no longer touch.

In 2017, the World Health Organization (WHO) published a list of 12 Multidrug resistant pathogen There is an urgent need for new active substances. The top priorities are Acinetobacter baumanni and Pseudomonas aeruginosa, as well as the above-mentioned carbapenem-resistant gut microbiota. For them, the new combination of the two antibacterial substances (azutreonam and avivactam) is seen as a sign of hope.

Beacon of hope for a particular resistance

“Aztreonam avivactam is a combination of the old antibiotic aztreonam and the new inhibitor avivactam, which can negate the effectiveness of resistance to carbapenem and make the bacterium vulnerable again,” JLU said. DZIF scientist Dr. Can Imirzalioglu explains. Co-author of the Institute of Medical Microbiology and Research. Especially against intestinal bacteria, the mechanism of resistance is based on a specific type of carbapenemase enzyme, so excellent effects are expected.So far, infections due to such carbapenem resistance Pathogen Treatment options with existing antibiotics are often very difficult because they are severely restricted or no longer exist, “adds the researchers.

Currently, the fixed combination of these two substances is not yet freely available as a treatment and is only used in clinical research. In Europe, Greece and Italy are one of the countries that have high hopes for the combination of Aztreonam and Abivactam. This type of carbapenemase is more widespread than in Germany. However, the incidence of carbapenem-resistant pathogens is steadily increasing worldwide. Against this background, a team led by Dr. Patrice Nordmann, a resistance researcher at the University of Friborg (Switzerland), was able to identify the mechanisms that lead to resistance to aztreonam-avivactam. In addition, they have already detected pathogens with these properties. Dr. Yancheng Yao, co-author of the study and DZIF scientist at the Institute for Medical Microbiology at JLU Giessen, explains these mechanisms as follows: Specific resistance gene. “

Studies detect early German resistance

A Giessen-based research group, in collaboration with Fribourg scientists, will be the first in Germany to detect such pathogens through bacterial genome analysis conducted as part of a surveillance study of highly resistant pathogens in Hessen. Now (SurvCARE). “I’m worried because this combination of active substances hasn’t been used clinically yet,” said Tori, director of the JLU Institute for Medical Microbiology and coordinator of healthcare-related and antibiotic research areas. Dr. Nadchakrabolti explains. Resistant bacterial infection in DZIF. “It is also alarming that this resistance has also been detected in bacteria that carry carbapenemase, which is very common in Germany. As a result, the potential for aztreonam-avivactam as an initial treatment is greatly limited. Infections Expectations as a desired combination in Germany may not be met by carbapenem-resistant pathogens, “the scientists conclude.

Studies currently published in journals Antibiotics and chemotherapyAlso points out the importance of genome-based surveillance of such pathogens. “Genome-based analysis of highly resistant pathogens is important not only for the analysis of outbreaks and infectious events, but also an important guard for the development of new resistance and early detection of new pathogens when used continuously. It also works, “says the professor. .. Dr. Linda Falgenhauer, co-author of the study, a DZIF scientist, and a professor of genome-based surveillance and epidemiology of multidrug-resistant pathogens at the JLU Institute of Hygiene and Environmental Medicine. The data collected was jointly exchanged in digital form to enable rapid access to significant developments in transregional or international relevance.

This study reiterates the importance of developing new antibiotics, which is the focus of DZIF. DZIF is a recently formed founding member. INCATE An initiative aimed at filling the pipeline of new drugs.

Provided by German Center for Infection Research