US FDA approves gepotidacin, a first-in-class antibiotic for UTIs in women
Gepotidacin has recently been approved by the US Food and Drug Administration (FDA) - the first in a new class of oral antibiotics for adult females with uncomplicated UTIs. This new treatment option is appropriate for uUTIs caused by: Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii complex, Staphylococcus saprophyticus, and Enterococcus faecalis. It has also been approved for use in children ≥12 years of age weighing at least 40 kg.
Gepotidacin is a first-in-class triazaacenaphthylene bacterial type II topoisomerase inhibitor with a novel mechanism of action; inhibiting bacterial DNA replication by blocking two essential topoisomerase enzymes. Mutations in both enzymes would likely be necessary for resistance to occur, raising hopes that the drug will be able to maintain long-term effectiveness and have a lower potential for resistance.
In two randomized clinical trials (EAGLE-2 and EAGLE-3), gepotidacin was noninferior to nitrofurantoin in both studies and superior to nitrofurantoin in EAGLE-3.[88]
Gepotidacin has the potential to cause QTc prolongation, so should be avoided in patients with a history of QTc prolongation, or those with relevant pre-existing cardiac disease, and in patients receiving drugs that prolong the QTc interval. It also should be avoided in patients taking strong CYP3A4 inhibitors, in patients with severe hepatic impairment (Child-Pugh Class C), and in patients with severe renal impairment (estimated glomerular filtration rate [eGFR] <30 mL/min).
Urinary tract infections (UTIs) are among the most common conditions encountered by clinicians across a range of settings. The development of gepotidacin marks a major milestone, as it is the first new oral antibiotic for UTIs in more than 20 years. It is anticipated that gepotidacin will be available in the US in the second half of 2025. Gepotidacin has not been approved in Europe as yet.
Summary
Definition
History and exam
Key diagnostic factors
- dysuria
- urinary frequency
- hematuria
- back/flank pain
- costovertebral angle tenderness
- fever
Risk factors
- sexual activity
- spermicide use
- postmenopause
- positive family history of UTIs
- history of recurrent UTI
- presence of a foreign body
- insulin-treated diabetes
- high lifetime number of UTIs
- recent antibiotic use
- poor bladder emptying
- increasing age
Diagnostic tests
Tests to consider
- postvoid residual (PVR)
- renal ultrasound
- abdominal/pelvic CT scan
- cystoscopy
Treatment algorithm
Contributors
Authors
Una J. Lee, MD
Female Pelvic Medicine and Reconstructive Surgery
Section of Urology and Renal Transplantation
Virginia Mason Medical Center
Seattle
WA
Disclosures
UJL declares that she has no competing interests.
Acknowledgements
Dr Una J. Lee would like to gratefully acknowledge Dr Elliot Blau for his contribution to this monograph, and Dr Bhavin N. Patel and Dr Howard B. Goldman, previous contributors to this topic.
Disclosures
EB, BNP, and HBG declare that they have no competing interests.
Peer reviewers
Priyanka Sharma, MD
Associate Staff
Cleveland Clinic Foundation
Cleveland
OH
Disclosures
PS declares that she has no competing interests.
Timothy J. Benton, MD
Associate Residency Director
Texas Tech University Health Sciences Center
Amarillo
TX
Disclosures
TJB declares that he has no competing interests.
Paul Little, BA (Oxon), MBBS, MRCP, MSc, FRCGP, MD
Professor of Primary Care Research
Community Clinical Sciences Division
University of Southampton
Southampton
UK
Disclosures
PL declares that he has no competing interests.
References
Key articles
European Association of Urology. EAU guidelines on urological infections. Mar 2025 [internet publication].Full text
Nicolle LE, Gupta K, Bradley SF, et al. Clinical practice guideline for the management of asymptomatic bacteriuria: 2019 update by the Infectious Diseases Society of America. Clin Infect Dis. 2019 Mar 21.Full text Abstract
Bent S, Nallamothu BK, Simel DL, et al. Does this woman have an acute uncomplicated urinary tract infection? JAMA. 2002 May 22-29;287(20):2701-10. Abstract
The American College of Obstetricians and Gynecologists. Urinary tract infections in pregnant individuals. Obstet Gynecol. 2023 Aug 1;142(2):435-45.Full text Abstract
Reference articles
A full list of sources referenced in this topic is available here.
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