by In 2022, 23,303 people died in Spain within 30 days of being diagnosed with an infection caused by multidrug-resistant bacteria (MRB), according to the study.SEIMC-BMR 2023‘. The World Health Organization (WHO), the misuse of antibiotics is reducing their effectiveness and generating resistant bacteria that could be responsible for 10 million deaths worldwide by 2050.
Therefore, the arrival of a new drug from a new class of antibiotics that has proven to be effective against a superbacteria that is multi-resistant to most antibiotics is great news to start 2024.
The compound belongs to a new class of antibiotics and is presented in two articles published in ‘Nature‘. At the moment, it has proven to be effective against a bacterial species that is resistant to multiple classes of existing antibiotics, Acinetobacter baumannii. Baumannii can be the causative agent of infections such as pneumonia, bacteremia, meningitis, urinary tract and soft tissue infectionsbeing associated with high mortality.
Drug-resistant bacterial infections represent an imminent threat to global public health and increasingly contribute to the deaths of infected people. Of particular concern are diseases caused by bacteria.Gram-negative«, since these microbes are wrapped in both internal and external membranes that are difficult for most antibiotics to penetrate.
Carbapenem-resistant Acinetobacter baumannii (CRAB) is particularly difficult to treat. For more than 50 years, no new classes of antibiotics have been approved for Gram-negative bacteria. Treatment options for CRAB infections continue to decline as mortality rates increase, with some estimated mortality rates reaching approximately 50% for invasive infections.
This superbacteria It is a major concern for the WHO, as it is classified as a priority 1 critical pathogen by said organization and an urgent threat to humans. Centers for Disease Control and Prevention from the US and Europe.
A. baumannii is a species of Gram-negative bacteria, which is difficult to eliminate because it has an outer membrane that contains lipopolysaccharides (LPS), which is resistant to the penetration of several antibiotics. Stopping LPS synthesis and its transport to the outer membrane reduces cell viability and may increase susceptibility to some antibiotics.
The new antibiotic discovered, identified by laboratory researchers Hoffmann-La Roche in Basel (Switzerland) and Harvard University (USA), is a macrocyclic peptide called zosurabalpin that shows promising antibacterial activity against CRAB.
Zosurabalpin prevents LPS from reaching the outer membrane of the bacteria by inhibiting the transport complex that facilitates its movement through the bilayer.
The future looks bright with the possibility that a new class of antibiotics is finally on the horizon
In the trials carried out, it has been seen that the drug effectively treats highly CRAB-resistant bacteria in the laboratory and in mouse models.
Furthermore, its activity against clinically resistant CRAB shows that zosurabalpin can circumvent existing resistance mechanisms, although the authors acknowledge that the possibility of the emergence of resistance to this new compound requires further investigation under clinically relevant conditions.
Tests on people
Based on the promising results obtained in the laboratory, clinical trials have begun in people carrying this super-resistant CRAB bacteria.
These studies will also serve to develop similar compounds directed against other Gram-negative bacteria.
“This discovery opens the door to targeting the LPS transport system of other problematic Gram-negative bacteria, such as Pseudomonas aeruginosa, Klebsiella pneumoniae and Escherichia coli», point out in a comment that accompanies the article Morgan Gugger and Paul Hergenrother, of the university of illinois (USA.).
But the studies, explain Gugger and Hergenrother, provide relevant information since it is recognized that the interruption of normal bacteria in the intestine (the microbiome) is harmful to human health; Such disturbance is a practical consequence of all antibiotics used clinically. «Given the high specificity of zosurabalpin for A. baumannii, it could be a microbiome-sparing antibiotic.», they point out.
The focus toward bacteria-specific antibiotics is a new development and may be facilitated by diagnostics that can rapidly identify specific harmful bacteria in infected individuals.
Because zosurabalpin is already being tested in clinical trials, the researchers write, “the future looks bright, with the possibility that a new class of antibiotics for invasive CRAB infections may finally be on the horizon.”
