Expert Insights: Q&A with Mark Ebell, MD, on Gepotidacin and UTI Management
Family physician and researcher Mark Ebell, MD, discusses the clinical implications, efficacy, and role of gepotidacin in UTI management.
The recent FDA approval of gepotidacin (Blujepa; GSK) introduces a novel treatment option for uncomplicated urinary tract infections (uUTIs) in female patients aged 12 and older. This approval marks the first introduction of a new class of oral antibiotics for uUTIs in nearly 30 years, addressing the growing concern of antibiotic resistance among uropathogens.
Gepotidacin operates through a unique mechanism, inhibiting bacterial DNA gyrase and topoisomerase IV, which are essential enzymes for bacterial replication. This distinct mode of action makes it effective against common uropathogens, including strains resistant to existing antibiotics. Nevertheless, the clinical emphasis remains on the drug's safety, efficacy, tolerability, and cost-effectiveness.
Despite its promise, the higher incidence of gastrointestinal side effects and anticipated higher cost position gepotidacin as a second- or third-line treatment option. Physicians should counsel patients on the benefits and risks associated with gepotidacin, considering individual patient circumstances and local antibiotic resistance patterns when selecting the most appropriate therapy.
Beyond the introduction of new antibiotics like gepotidacin, advancements in rapid, accurate, and cost-effective diagnostic tools are essential. To gain further insight into the challenges of managing uncomplicated UTIs and how gepotidacin fits into the evolving treatment landscape, we spoke with Mark H. Ebell, MD, deputy editor of the journal American Family Physician and a professor in the Department of Epidemiology and Biostatistics in the College of Public Health at the University of Georgia. In the following interview, Dr Ebell shares his perspectives on current gaps in UTI diagnosis and treatment, the role of gepotidacin, and the future of UTI management.
Patient Care: What are the most significant challenges physicians currently face in managing uUTIS, particularly concerning antibiotic resistance and treatment failures?
Mark H. Ebell, MD: Physicians don’t order a urine culture for someone with an uUTI, and we also don’t generally have access to knowledge about antibiotic resistance rates in the community. We generally choose a first-line antibiotic based on guidelines, something like fosfomycin or nitrofurantoin.
Patient Care: Beyond just bacterial eradication, what are the key unmet needs in the management of uUTIs from a physician perspective?
Dr Ebell: The diagnosis is primarily based on symptoms and urine dipstick testing, occasionally supplemented by urine microscopy, though that practice has declined due to time constraints and training requirements. A rapid, accurate, and inexpensive diagnostic test—similar to those available for strep throat or COVID-19—would be great, especially if it could provide information about drug resistant strains.
Patient Care: The recently approved gepotidacin is being hailed as a breakthrough treatment as it comes at a time when bacteria are becoming increasingly resistant to standard antibiotics. What are the key differentiating factors of gepotidacin's mechanism of action compared to other commonly prescribed oral antibiotics for uUTIs?
Dr Ebell: Gepotidacin uses a different mechanism than other antibiotics, inhibiting DNA gyrase and topoisomerase IV. While that’s a good marketing point, what really matters to physicians and their patients is whether it is safe, effective, and well tolerated at a reasonable cost.
Patient Care: How does the efficacy and safety profile of gepotidacin, as demonstrated in clinical trials, compare to current first-line treatments for uUTIs?
Dr Ebell: So far it has only been compared to nitrofurantoin, and it was found to be similar in efficacy in one study and slightly better in another. Adverse gastrointestinal (GI) effects were pretty common thoughwith gepotidacin—diarrhea occurred in 16% of patients, and nausea or vomiting in 11%. These rates are notably higher than those associated with nitrofurantoin (3% and 4%, respectively).
Patient Care: How should primary care physicians counsel patients about gepotidacin, including its benefits, risks, and potential alternatives?
Dr Ebell: Gepotidacin seems to be similar in efficacy to other first-line antibiotics including pivmecillinam, which was just approved in April 2024. The somewhat higher rate of GI side effects and the much higher cost make it a second- or third-line drug in my opinion.
Patient Care: Beyond new antibiotics, what other advancements or strategies (eg, diagnostics, preventative measures) do you believe hold promise for improving the management of uUTIs?
Dr Ebell: As I said, we need better ways to identify those patients who appear to have a uUTI but who are in reality at risk for hospitalization. A diagnostic test that helps us rapidly identify a pathogen and its susceptibility profile would also be helpful. Of course, these things have to be reasonable in cost as well.
