A Dark Horse in the Antibiotic World is Coming! Probably the Ultimate Weapon to Snipe Super-strong Bacteria

On April 5, 2024, a new study from a Swedish university caused a stir in the scientific community. Scientists have discovered a new class of antibiotics with potent activity against multidrug-resistant bacteria and successfully cured bloodstream infections in mice. The findings, published in the scientific journal Proceedings of the National Academy of Sciences, have sparked new hopes for antibiotic development. This article provides a detailed analysis of this.

▲Why the discovery of new antibiotics is so important for the future of mankind

Since the discovery of penicillin, antibiotics have been the cornerstone of modern medicine, and over the past century, they have dramatically improved the quality of life for people across the globe. However, with antibiotic resistance on the rise, our reliance on antibiotics is also facing significant challenges. Currently, resistance to gram-negative bacteria is a serious global problem, and many traditional broad-spectrum antibiotics have lost their effectiveness against these bacteria.

The discovery of new antibiotics is of great significance to mankind. As antibiotic resistance continues to increase, the search for new antibiotics is key to addressing this challenge. These new antibiotics can not only expand treatment options and improve the success rate of infectious diseases, but also reduce the risk of infection during surgery and medical procedures, thereby safeguarding public health and improving quality of life. Therefore, in order to ensure that effective antibiotics are still available in the future, it is essential to develop new therapies that are less susceptible to drug resistance.

▲What kind of new antibiotic is this? What is the pharmacological mechanism?

The antibiotics found in this study have potent antimicrobial activity against gram-negative bacteria by targeting the lipopolysaccharide synthesis pathway of bacteria. This pathway is necessary in most gram-negative bacteria and there is no analogue in humans, so this class of antibiotics is selective for bacteria. This new class of antibiotics acts on a protein called LpxH, which synthesizes the outermost protective layer, lipopolysaccharides, in gram-negative bacteria. These antibiotics have shown great potential for the successful treatment of bloodstream infections in mouse models with high activity against multidrug-resistant bacteria.

Specifically, this class of antibiotics is optimized to be active against wild-type bacterial strains (with efflux function) and can effectively inhibit bacteria expressing drug-resistant genes such as broad-spectrum β-lactamase, metallo β-lactamase, and carbapenemase. There is no pre-existing resistance in clinical isolates, so it is still effective against "superbugs" that have evolved in the direction of current resistance mechanisms. In vivo, it has a strong effect on bloodstream infections caused by E. coli and Klebsiella. In conclusion, this new class of antibiotics is characterized by specificity, potency, and lack of existing resistance, which is expected to provide a new solution to the challenge of antibiotic resistance. 

▲ Expectations are great, but there is still a long way to go for it to become a successful new drug

In fact, in the real world of new drug development, this research has only just begun. Determining the time required for research and development of new classes of antibiotics is complex and involves multiple phases. First, researchers need to conduct laboratory studies to understand the mechanism, activity, and toxicity of antibiotic classes, which can take years. The new drug investigator then conducts a preclinical study of an animal model to evaluate its efficacy and safety, which can take several years.

Subsequently, clinical trials are conducted, which are generally divided into 4 phases, to evaluate the effect, safety and dosage in humans, which take several years. Finally, if the clinical trial results are satisfactory, an application for regulatory approval is submitted, but the approval time varies by region and can take several years. Therefore, it generally takes at least 5 years or more for a new antibiotic class to be widely used.

▲ Summary

Taken together, this new class of antibiotics shows great potential and exciting future trends because they target entirely new bacterial targets. It is a class of antibiotics with targeted and potent activity and can be used to treat a wide range of gram-negative bacterial infections, such as bloodstream infections, respiratory tract infections, and urinary tract infections. In addition, it can be used in combination with other antibiotics to improve the therapeutic effect and reduce the development of drug resistance. This new antibiotic presents great potential compared to antibiotics currently in clinical development. 

References1

1. Huseby DL, Cao S, Zamaratski E, et al. Antibiotic class with potent in vivo activity targeting lipopolysaccharide synthesis in Gram-negative bacteria. 2024; 121(15): e2317274121.