An ongoing dialogue on HIV/AIDS, infectious diseases,
April 3rd, 2025
Gepotidacin — New Antibiotic or Rare Tropical Bird?
A Blujepa! (Drawing by Anne Sax.)
Imagine you’re birdwatching in the Costa Rican rainforest, Merlin app in hand. A flash of iridescent blue catches your eye. You scan the canopy and whisper excitedly:
Look, it’s the elusive Blujepa! A rare sighting!
No, not a real bird, but the brand name of gepotidacin, something rarer — and arguably more exciting — than a tropical bird, at least to us ID geeks: a brand new antibiotic class for treatment of uncomplicated urinary tract infections. That’s right, a first-in-class triazaacenaphthylene antibiotic, approved by the FDA on March 25 for the treatment of uncomplicated urinary tract infections (uUTIs).
(If you’re wondering about pronunciation, I have on good authority it’s, JEP-oh-TIE-dah-SIN. Say it fast — it kind of sounds like an obscure progressive rock band, doesn’t it? Pretty sure Gepotidacin opened for Emerson, Lake & Palmer in 1974.)
Approval of the drug was the direct result of favorable clinical trials, EAGLE-2 and EAGLE-3. (Yes, more birds. You’d think this antibiotic came with feathers.) In both of these studies, 5 days of gepotidacin was noninferior to nitrofurantoin; in EAGLE-3, it also met criteria for superiority. The most common side effect was diarrhea, but it was overall well-tolerated.
So cue the ID fanfare.
(Muted trumpets only—we ID docs must always maintain antimicrobial stewardship mode. And let’s be honest — no one really knows what a “triazaacenaphthylene antibiotic” is, but that seems to be the convention to cite the biochemical structure of new antibiotics, as if any of us speak that language. Linezolid was frequently introduced as “the first oxazolidinone antibiotic”, whatever that means.)
To put this gepotidacin approval into context: the last time we had a new class of antibiotics for this indication, people were listening to Genesis and Yes and ELP on cassette tapes — maybe even 8-track tapes if you were stuck driving around your beat-up Chevy Nova. Since then, our therapeutic options have largely consisted of dusting off the same old standbys — TMP-SMX, nitrofurantoin, and if needed, fosfomycin or a fluoroquinolone. The last of these, of course, has tumbled out of favor, what with the tendons, the CNS effects, the QT issues, and the black box warnings piling up on your bedside table like overdue library books. And fosfomycin isn’t really that effective, is it?
Enter gepotidacin. Not only is it orally bioavailable — always a win for treating UTIs outside the hospital — but it also has activity against some resistant gram negatives that have increasingly shrugged off our old reliables. The drug inhibits bacterial DNA replication by targeting two essential bacterial enzymes: DNA gyrase and topoisomerase IV. This dual inhibition mechanism is unique, and different enough (we hope) from quinolones to limit cross-resistance.
Of course, the excitement is tempered by the usual caveats:
- the approval is currently for uncomplicated UTIs only
- it won’t be cheap (pricing is not available yet, but one can presuppose)
- the package insert includes a warning about avoiding the drug in people with QT prolongation — a caveat that also applies to quinolones.
Finally, approval of any new antibiotic is accompanied by the low-level anxiety that overuse will have us back where we started by the time we learn how to pronounce it properly.
Still, if gepotidacin can keep some patients with resistant E. coli out of the hospital and away from IV carbapenems, that’s a net win.
And if the distinctive call of the Blujepa brings to mind Rick Wakeman noodling through a virtuosic keyboard solo, well, that’s just a bonus. Take it away, Rick!
Ok, I’ll stop now. This is getting way too silly.
Paul E. Sax, MD
Contributing Editor
NEJM Journal Watch
Infectious Diseases
Biography | Disclosures | Summaries
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