FDA approves new oral antibiotics effective against resistant strains of gonorrhea
Two new oral antibiotics, zoliflodacin and gepotidacin, have been approved by the Food and Drug Administration (FDA) for treating patients with uncomplicated urogenital gonorrhea in patients age 12 years and older. The gepotidacin approval is restricted to patients with few or no other treatment choices because of limited safety data.
Zoliflodacin and gepotidacin have novel mechanisms of action, which means they are effective against strains of Neisseria gonorrhoeae that are resistant to currently recommended antibiotics. Gepotidacin and zoliflodacin act by inhibiting bacterial DNA replication.
The new antibiotics provide oral treatment options and alternative treatments for resistant strains of N gonorrhoeae.
Summary
Definition
Inflammation of the urethra, usually caused by a STI or, less often, by trauma or a chemical irritant. Urethritis typically presents as dysuria, urethral discharge, and/or pruritus at the end of the urethra. Urethral discharge is the classic physical finding. Women may have associated cervicitis or vaginitis, presenting with vaginal discharge and/or bleeding.[1][2][3]
Clinical diagnosis of urethritis may be based on observation of urethral discharge on exam, along with abnormal numbers of polymorphonuclear leukocytes on Gram stain of urethral discharge, or microscopy of urine sediment, or positive urine leukocyte esterase test.[1]
Urethritis is categorized as GU if N gonorrhoeae is isolated; NGU if N gonorrhoeae is not isolated. The most common etiologic agents in NGU are C trachomatis and Mycoplasma genitalium.[1]
This topic focuses on infectious causes of urethritis.[Figure caption and citation for the preceding image starts]: Gonorrhea with penile meatal dischargeCDC Image Library; Susan Lindsley [Citation ends].
History and exam
Key diagnostic factors
- urethral discharge
- urethral erythema, irritation and/or itching
- dysuria
- vaginal discharge and/or bleeding
Other diagnostic factors
- orchialgia
- testicular or epididymal pain
- pelvic pain (women)
Risk factors
- age 15-24 years
- men who have sex with men
- new or multiple sex partners
- prior or current STI
- unprotected sex
- circumcision
Diagnostic tests
1st tests to order
- Gram stain of urethral discharge
- urinalysis
- nucleic acid amplification testing
- HIV test
- syphilis test
Tests to consider
- urine flow cytometry
- urine culture
- nucleic acid amplification testing for Trichomonas vaginalis
- wet mount or culture for Trichomonas vaginalis
- extragenital nucleic acid amplification testing
- nucleic acid amplification testing for other organisms
- potassium hydroxide prep of urethral discharge
- antibiotic susceptibility testing
Treatment algorithm
presumptive diagnosis: nonpregnant
presumptive diagnosis: pregnant
confirmed urethritis: nonpregnant
confirmed urethritis: pregnant
recurrent or resistant urethritis
Contributors
Authors
Lisa Istorico Sanders, MD
Associate Professor
Pediatric Infectious Diseases
University of South Florida Morsani College of Medicine
Executive Director
Ybor Youth Clinic
Tampa, FL
Disclosures
LIS is part of the Adolescent Medicine Trials Network grant at the University of South Florida Department of Pediatrics. LIS is involved in a study (ATN 173) of doxycycline prophylaxis for sexually transmitted infections (STIs) in those identified as female at birth at risk for acquiring STIs.
Acknowledgements
Dr Lisa Istorico Sanders would like to gratefully acknowledge Dr Sheldon Morris and Dr Christina Bailey previous contributors to this topic.
Disclosures
CB declares that she has no competing interests.
Peer reviewers
Vani Dandolu, MD, MPH
Associate Professor
Ob/Gyn and Urology
Director
Division of Urogynecology
Associate Residency Program Director
Temple University Hospital
Philadelphia, PA
Disclosures
VD declares that he has no competing interests.
Khalil Ghanem, MD, PhD
Assistant Professor of Medicine
Associate Fellowship Program Director
Division of Infectious Diseases
Johns Hopkins University School of Medicine
Baltimore, MD
Disclosures
KG declares that he has no competing interests.
Christopher Fairley, PhD
Professor of Sexual Health
University of Melbourne
Director
Melbourne Sexual Health Centre
Carlton
Victoria
Australia
Disclosures
CF is an author of a number of references cited in this topic. CF has received program grants of 6 figures US$.
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.
References
Key articles
Workowski KA, Bachmann LH, Chan PA, et al. Sexually transmitted infections treatment guidelines, 2021. MMWR Recomm Rep. 2021 Jul 23;70(4):1-187.Full text Abstract
Crofts M, Blee K, Evans C, et al. British Association of Sexual Health and HIV national guideline on the management of non-gonococcal urethritis (NGU), 2026. Int J STD AIDS. 2026 Jun;37(7):690-703.Full text Abstract
European Association of Urology. Guidelines on urological infections. Mar 2026 [internet publication].Full text
Soni S, Fifer H, Al-Shakarchi Y, et al. British Association of Sexual Health and HIV national guideline for the management of infection with Mycoplasma genitalium, 2025. Int J STD AIDS. 2026 May;37(6):576-88.Full text Abstract
Horner PJ, Blee K, Falk L, et al; International Union against Sexually Transmitted Infections. 2016 European guideline on the management of non-gonococcal urethritis. Int J STD AIDS. 2016 Oct;27(11):928-37.Full text
Reference articles
A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.
Differentials
- Urinary tract infection
- Candida balanitis or vaginitis
- Noninfectious urethritis
More DifferentialsGuidelines
- Guidelines on urological infections
- Canadian guidelines on sexually transmitted and blood-borne infections
More GuidelinesPatient information
Chlamydia
Gonorrhea
More Patient information
Log in or subscribe to access all of BMJ Best Practice
Use of this content is subject to our disclaimer