A new class of antibiotic for the treatment of urinary tract infections is about to hit pharmacies.
And unlike most of the drugs we know, this one is not as susceptible to the plague of antibiotic resistance.
Gepotidacin was developed by a group of researchers from Venderbilt University (USA), in partnership with biopharmaceutical company Glaxo Smith Kline.
The results obtained in the two studies have been submitted to the Food and Drug Administration (FDA), where they are awaiting approval.
If the result is positive, gepotidacin will become the first antibiotic to be approved for use in humans in decades.
In recent years, science has been focused on discovering new antibiotics. However, the truth is that the vast majority of candidates do not pass all the clinical trials required to be approved.
For this reason, if gepotidacin is approved, it will be a great victory for science (and for all of us).
In the two trials carried out, EAGLE-2 and EAGLE-3, gepotidacin therapy proved to be very effective. Not only were the results not inferior to those obtained with nitrofurantoin, an antibiotic commonly used as first-line treatment for patients with urinary tract infections, but they were even superior.
In EAGLE-2, around 50.6% of patients treated with gepotidacin managed to stop the infection developing. Nitrofurantoin, on the other hand, had a success rate of 47% in the same study. In EAGLE-3, the success rate was 58.5% for gepotidacin, compared to 43.6% with nitrofurantoin.
The first study in which these results were published became one of the most read articles of the last 10 years in the journal ACS Infectious Diseases, where it was published, which reinforces the importance of these results and the potential of this antibiotic at a time when antibiotic resistance has become a serious public health problem.
"Overall, the results of the EAGLE-2 and EAGLE-3 trials provide strong evidence that gepotidacin is an effective and safe oral antibiotic for the treatment of uncomplicated urinary tract infections," explain the study's authors.
"Gepotidacin has all the potential to become a new treatment, especially for patients who are resistant to other antibiotics or intolerant of first-line treatments," they add.
But the importance of gepotidacin lies not only in its efficiency as an antibiotic, but also in its ability not to generate resistance so easily. To better understand this characteristic, it's important to understand how antibiotic resistance develops.
When an antibiotic is used on a large scale over a long period of time, there is a possibility that the bacteria it acts on will become resistant to the antibiotic: the drug stops working and can no longer control the infection.
As a result, the bacteria multiply, the infection increases and the antibiotic is completely ineffective. In these cases, the bacterium is said to have gained resistance to the antibiotic.
But how does this work in practice? For an antibiotic to work, it has to bind to the bacteria it is going to fight. What happens when a bacterium gains resistance is that it acquires a genetic mutation that means the antibiotic can no longer bind.
Now, if the drug doesn't bind to its target, then its action will obviously be null. Since the bacteria with the mutation are at an advantage in terms of survival, they end up multiplying exponentially, until a point is reached where all the bacteria have this mutation and, therefore, all the bacteria in that strain are resistant to the antibiotic.
But even when it comes to antibiotic resistance, gepotidacin has the edge. This is because its mechanism of action involves binding to two enzymes in the bacteria (topoisomerase gyrase type II and topoisomerase IV).
In other words, for a bacterium to become resistant to gepotidacin, it has to accumulate at least two mutations in these specific proteins, which is much less likely to happen.
"This discovery is critical because it means that in order to become resistant to geoptidacin, there must be simultaneous mutations in two different enzymes. This makes the development of resistance much less likely," says Neil Osheroff, a researcher at Venderbilt University and lead author of the study.
"Once gepotidacin enters regular clinical use, and as evidence of its use begins to emerge, signs of resistance should be monitored," adds Osheroff.
" Health economics must be developed in such a way as to moderate clinical enthusiasm for new antibiotics, in order to control the episodes of resistance that arise above all from unbridled and often unnecessary use," explains the study's author in a final note.
