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
Definição
História e exame físico
Principais fatores diagnósticos
- dysuria
- urinary frequency
- hematuria
- back/flank pain
- costovertebral angle tenderness
- fever
Outros fatores diagnósticos
- urinary urgency
- suprapubic pain and tenderness
Fatores de risco
- 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
Investigações diagnósticas
Primeiras investigações a serem solicitadas
- urine dipstick
- urine microscopy
- urine culture and sensitivity
Investigações a serem consideradas
- postvoid residual (PVR)
- renal ultrasound
- abdominal/pelvic CT scan
- cystoscopy
Algoritmo de tratamento
uncomplicated
complicated suitable for outpatient therapy: not pregnant
complicated suitable for outpatient therapy: pregnant
complicated requiring inpatient therapy: not pregnant
complicated requiring inpatient therapy: pregnant
uncomplicated recurrent (3 or more in 12 months): related to sexual intercourse
uncomplicated recurrent (3 or more in 12 months): unrelated to sexual intercourse
Colaboradores
Autores
Una J. Lee, MD
Female Pelvic Medicine and Reconstructive Surgery
Section of Urology and Renal Transplantation
Virginia Mason Medical Center
Seattle
WA
利益声明
UJL declares that she has no competing interests.
鸣谢
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.
利益声明
EB, BNP, and HBG declare that they have no competing interests.
同行评议者
Priyanka Sharma, MD
Associate Staff
Cleveland Clinic Foundation
Cleveland
OH
利益声明
PS declares that she has no competing interests.
Timothy J. Benton, MD
Associate Residency Director
Texas Tech University Health Sciences Center
Amarillo
TX
利益声明
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
利益声明
PL declares that he has no competing interests.
Peer reviewer acknowledgements
BMJ Best Practice topics are updated on a rolling basis in line with developments in evidence and guidance. The peer reviewers listed here have reviewed the content at least once during the history of the topic.
Disclosures
Peer reviewer affiliations and disclosures pertain to the time of the review.
参考文献
关键文献
European Association of Urology. EAU guidelines on urological infections. Mar 2025 [internet publication].全文
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.全文 摘要
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. 摘要
The American College of Obstetricians and Gynecologists. Urinary tract infections in pregnant individuals. Obstet Gynecol. 2023 Aug 1;142(2):435-45.全文 摘要
参考文献
A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.
鉴别诊断
- Asymptomatic bacteriuria
- Pyelonephritis
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