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Urethritis

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Here is a thorough overview of urethritis drawn from multiple authoritative sources.

Urethritis

Definition

Urethritis is inflammation of the urethra, most commonly caused by sexually transmitted pathogens. Typical symptoms include urethral discharge, dysuria, urethral stinging or itching, and penile tip irritation, though many cases are entirely asymptomatic. There are an estimated 2.8 million cases annually in the United States.

Classification

Urethritis is divided into two major categories:
TypeCauseKey Features
Gonococcal Urethritis (GU)Neisseria gonorrhoeae~5-20% of urethritis cases; profuse, purulent (white/yellow/green) discharge
Non-Gonococcal Urethritis (NGU)C. trachomatis, M. genitalium, others~80-95% of urethritis cases; thin, clear or gray discharge
Urethral discharge comparison - A: Gonococcal (purulent), B: Non-gonococcal (clear/thin)
A: Gonococcal urethritis discharge (purulent). B: Non-gonococcal urethritis discharge (thin, clear). (Courtesy Stephanie N. Taylor, MD) - Goldman-Cecil Medicine

Etiology of NGU

The causative organisms of NGU in order of frequency:
  1. Chlamydia trachomatis - 15-40% of NGU cases; most common in men under 24
  2. Mycoplasma genitalium - 15-25% of symptomatic NGU; 20-30% of persistent/recurrent cases
  3. Trichomonas vaginalis - prevalence varies widely by region (2-13%)
  4. Ureaplasma urealyticum - weak association, consider when no other pathogen identified
  5. HSV-1, HSV-2, adenovirus - less common causes
  6. Idiopathic - many men have no definitive pathogen identified

Clinical Features

Symptoms:
  • Urethral discharge (purulent in GU, mucopurulent or clear in NGU)
  • Dysuria
  • Urethral burning, itching, or stinging
  • Meatal irritation/erythema
  • Often asymptomatic (especially in women and ~10% of men with GU)
Gonococcal urethritis: Incubation 2-6 days; profuse, purulent discharge; meatal erythema; penile lymphedema can occur.
Non-gonococcal urethritis: Symptoms generally less prominent; clinical features alone cannot reliably distinguish from GU - coinfection is common.

Diagnosis

Urethritis can be confirmed by any of the following:
  1. Mucoid, mucopurulent, or purulent discharge on examination
  2. Gram stain of urethral secretions showing ≥2 WBCs per oil immersion field (CDC updated threshold - previous threshold of ≥5 WBC/hpf missed significant chlamydia and gonorrhea cases)
  3. Positive leukocyte esterase on first-void urine
  4. >10 WBCs/hpf from first-void urine
Gram stain findings:
  • Gram-negative intracellular diplococci = presumptive N. gonorrhoeae (diagnostic in symptomatic men; sensitivity limited, so negative result does not rule out)
  • ≥2 WBCs with no intracellular diplococci = NGU
NAATs (Nucleic Acid Amplification Tests):
  • Preferred method for detecting both N. gonorrhoeae and C. trachomatis (highest sensitivity)
  • First-catch urine is the preferred specimen in males
  • NAATs also available for T. vaginalis and M. genitalium (no FDA-approved M. genitalium NAAT yet)
  • Note: NAATs are NOT FDA-cleared for rectal, oropharyngeal, or conjunctival gonorrhea - culture is preferred in those sites and in cases of sexual assault
When to culture: Suspected treatment failure, sexual assault in prepubescent patients, antimicrobial resistance surveillance.

Treatment

Gonococcal Urethritis

Current CDC-recommended regimen (note: resistance has driven regimen changes over the years):
  • Ceftriaxone 500 mg IM single dose (1 g if weight ≥150 kg) - the mainstay
  • If ceftriaxone unavailable: Cefixime 400 mg PO + Azithromycin 1 g PO (both in single doses)
  • Cephalosporin allergy: Azithromycin 2 g PO once + gemifloxacin 320 mg PO OR gentamicin 240 mg IM
Important note: Treat for chlamydia co-infection empirically if not ruled out by NAAT.

Non-Gonococcal Urethritis

First-line (initial episode):
  • Doxycycline 100 mg PO twice daily for 7 days (preferred per Rosen's EM; higher cure rates for M. genitalium)
  • OR Azithromycin 1 g PO single dose (cure rates for M. genitalium have dropped from 85% to ~40% due to resistance)
Alternative regimens:
  • Erythromycin base 500 mg PO QID x 7 days
  • Levofloxacin 500 mg PO once daily x 7 days
  • Ofloxacin 300 mg PO twice daily x 7 days

Treatment Algorithm for NGU

NGU treatment algorithm - initial and recurrent/persistent management
Treatment algorithm for NGU. (Campbell-Walsh-Wein Urology)

Persistent or Recurrent NGU

Consider resistant M. genitalium or T. vaginalis. Distinguish between:
  • Non-adherence or re-exposure to untreated partner - Repeat the initial regimen
  • Treatment failure despite completion and no re-exposure:
    • If azithromycin was used initially: Moxifloxacin 400 mg PO daily x 7-14 days
    • If doxycycline was used initially: Azithromycin 1 g PO x 1 dose
    • In areas of high T. vaginalis prevalence: Add Metronidazole 2 g PO once OR Tinidazole 2 g PO once

Trichomoniasis (when T. vaginalis identified)

  • Metronidazole 2 g PO once OR Tinidazole 2 g PO once

Complications

ComplicationNotes
EpididymitisMost common; unilateral pain/swelling; treat with ceftriaxone 500 mg IM + doxycycline 100 mg BID x 10 days
OrchitisOften accompanies epididymitis (epididymo-orchitis)
Prostatitis
Proctitis
Pelvic Inflammatory Disease (PID)In women with ascending infection; risk of tubal scarring, infertility, ectopic pregnancy
Disseminated Gonococcal Infection (DGI)Rare; treat with ceftriaxone 1 g IV/IM every 24 hours
Reiter SyndromePost-chlamydial reactive arthritis
Periurethral abscess / penile cellulitisUsually responds to standard single-dose GU treatment

Partner Management

  • Partners with sexual contact within the preceding 60 days should be referred for evaluation, testing, and presumptive treatment
  • Patients should abstain from intercourse for 7 days after single-dose treatment, or until completion of multi-day therapy with symptom resolution
  • Screen concurrently for gonorrhea, chlamydia, syphilis, HIV (and trichomoniasis where appropriate)
  • 3-month re-testing is recommended (not a test of cure at <3 weeks due to residual nucleic acids)

Special Considerations

Antimicrobial resistance: A major and growing challenge.
  • N. gonorrhoeae has developed resistance to penicillin, tetracycline, fluoroquinolones, and azithromycin - ceftriaxone remains the mainstay
  • M. genitalium is increasingly resistant to azithromycin; moxifloxacin is the rescue agent
  • The CDC's Gonococcal Isolate Surveillance Project (GISP) monitors trends
Women: Often asymptomatic for both GU and NGU; may present with cervicitis or sequelae (PID). NAATs of first-void urine or self-collected vaginal swab are the standard.
HIV: HIV status does not change antibiotic regimens for urethritis.
Sources: Campbell-Walsh-Wein Urology; Goldman-Cecil Medicine; Rosen's Emergency Medicine; Tintinalli's Emergency Medicine
Recent guideline note (2026): A 2026 German practice guideline (PMID 41779165) provides a practical update on urethritis management - the core treatment framework above remains consistent with current standards, though monitoring local resistance patterns for M. genitalium and N. gonorrhoeae is increasingly emphasized.
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