Scientists find first new antibacterial class in decades

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Urinary tract infections (UTIs) are a common problem, with up to 60% of women experiencing at least one in their lifetime. These infections are not only uncomfortable but can also lead to more serious health issues.

Traditionally, antibiotics have been the go-to solution, but with the rise of drug-resistant bacteria, finding effective treatments has become increasingly difficult. However, researchers at Vanderbilt University are making significant progress in this battle.

Led by Professor Neil Osheroff, a distinguished biochemist, the Vanderbilt team has been exploring a promising new antibacterial drug called gepotidacin. This drug represents a potential breakthrough in the treatment of UTIs, primarily caused by the bacterium Escherichia coli (E. coli).

The innovative aspect of gepotidacin is how it targets the bacteria. Most antibiotics focus on a single target within the bacteria, but gepotidacin goes a step further by attacking two critical enzymes, gyrase and topoisomerase IV.

These enzymes are essential for the bacteria’s DNA to function correctly. By inhibiting both enzymes simultaneously, gepotidacin significantly reduces the likelihood that the bacteria will develop resistance to the drug.

This dual targeting is a game-changer in antibiotic design because it means the bacteria would need to mutate in two separate places at the same time to resist the drug, a much less likely scenario.

The Vanderbilt researchers, in collaboration with the global biopharma company GlaxoSmithKline, have conducted a detailed study of how gepotidacin works against E. coli and the mechanisms behind potential drug resistance.

Their findings have been so compelling that they are part of the application to the Food and Drug Administration (FDA) for approval of gepotidacin as a treatment for UTIs in humans. If approved, gepotidacin would be the first new class of antibacterials introduced for human use in decades.

This research comes at a critical time. The rise of antibiotic-resistant bacteria is a global health threat, making the development of new treatments more urgent than ever.

The clinical trials for gepotidacin, reported in the prestigious medical journal The Lancet, have shown promising results. The trials, named EAGLE-2 and EAGLE-3, demonstrated that gepotidacin is not only effective in treating UTIs but also safe for oral use.

This is particularly good news for patients who either cannot tolerate existing antibiotics or for whom those antibiotics are no longer effective due to resistance.

Despite the excitement around gepotidacin’s potential, the authors of the clinical trial commentary urge caution. They highlight the importance of monitoring for any signs of emerging resistance to the drug once it is in regular use.

They also call for health economic analyses to ensure that the enthusiasm for this new antibiotic is balanced with an understanding of its best application in medical practice.

The work of the Vanderbilt team and their collaborators marks a significant stride towards combating bacterial infections in an era of increasing antibiotic resistance.

Gepotidacin’s development not only offers hope for those suffering from UTIs but also exemplifies the innovative approaches being taken to overcome one of the most pressing health challenges of our time.

The research findings can be found in ACS Infectious Diseases.

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