Urethritis

Urethritis is an inflammation of the urethral mucosa. In men, this is most commonly caused by sexually transmitted pathogens, notably Chlamydia trachomatis, Neisseria gonorrhoeae, and Mycoplasma genitalium. Patients are often asymptomatic but may present with urethral discharge, dysuria, and/or itching of the urinary meatus. Diagnostics include initial microscopy of urethral secretions to confirm urethritis and distinguish between gonococcal and nongonoccal etiologies, followed by nucleic acid amplification testing (NAAT) of first-void urine for gonorrhea and chlamydia. If same-day NAAT is available, treatment is tailored to the specific pathogen. If only same-day microscopy is available, empiric treatment is provided with ceftriaxone and doxycycline for gonococcal urethritis and either doxycycline or azithromycin for nongonococcal urethritis. Evaluation and treatment of all recent sexual partners is necessary to prevent recurrent infections.

This article outlines the management of urethritis in men. In women, urethritis has a broader differential diagnosis that includes urinary tract infection, sexually transmitted infections, and genitourinary syndrome of menopause; diagnostics and treatment should be tailored to the likely etiology.

Urethritis is usually a symptom of sexually transmitted infection (STI); coinfections are common.

Common etiologies ^[1][2]

• Gonococcal urethritis: N. gonorrhoeae
• Nongonococcal urethritis ^[1]
  • C. trachomatis: most common cause of urethritis ^[3]
  • Causes of nonchlamydial nongonococcal urethritis include:
    • Mycoplasma genitalium
    • Trichomonas vaginalis
    • Gram-positive cocci
    • Ureaplasma spp.
    • Herpes simplex virus types 1 and 2
    • Adenovirus
    • Noninfectious etiologies ^[4]
      • Repeated urethral manipulation (e.g., during catheterization)
      • Chemical irritation (e.g., from soap or spermicides)
      • Inflammatory conditions (e.g., lichen sclerosis)

Risk factors for infectious urethritis

• Unprotected sexual intercourse
• Multiple sexual partners
• History of other STIs ^[5]

• Dysuria
• Burning or itching of the urethral meatus
• Urethral discharge: purulent, cloudy, blood-tinged, or clear
• Initial hematuria
• General symptoms (e.g., fever, chills, or myalgia) are uncommon in urethritis and should raise suspicion for complications (see “Complications” below).

Urethritis, especially nongonococcal urethritis, may be asymptomatic.

Approach ^[1][6]

• Perform a clinical evaluation for STIs.
• Confirm urethritis, ideally with point-of-care microscopy.
• Obtain NAAT for gonorrhea and chlamydia and screen for other STIs.
• Consider further tests depending on clinical symptoms and local prevalence of STIs.

Confirmation of urethritis ^[1]

• Preferred: point-of-care urethral smear microscopy with Gram stain, methylene blue (MB) stain, or gentian violet (GV) stain
  • Urethritis is confirmed if there are ≥ 2 WBCs per oil immersion field. ^[1]
  • If either of the following are present, make a presumptive diagnosis of gonococcal urethritis:
    • Gram-negative intracellular diplococci on Gram stain
    • Intracellular purple diplococci on MB or GV stain
  • If urethritis is confirmed but diplococci are not detected, make a presumptive diagnosis of nongonococcal urethritis.
• Alternative methods
  • First-void urine with either:
    • Positive leukocyte esterase test
    • ≥ 10 WBCs/hpf on examination of urine sediment
  • Clinical confirmation of mucoid, mucopurulent, or purulent urethral discharge

Symptoms of urethritis with no organism on Gram stain of a urethral specimen suggest nongonococcal urethritis (e.g., infection with C. trachomatis or M. genitalium).

Additional studies ^[1]

• All patients
  • NAAT of first-void urine for gonorrhea and chlamydia ^[1]
  • Screening for other STIs, including HIV and syphilis
• Specific indications: Consider selected additional studies.

All patients with any symptoms of urethritis should receive NAAT for gonorrhea and chlamydia. ^[1]

Because coinfection with other genitourinary tract infections is possible, the presence of one infection does not rule out urethritis.

• Acute cystitis
• Epididymitis
• Prostatitis
• Chronic pelvic pain syndrome

The differential diagnoses listed here are not exhaustive.

Approach ^[1][6]

• Start antimicrobial therapy immediately.
  • Same-day results available: Treat the underlying cause of urethritis, e.g., antibiotics for gonorrhea, antibiotics for genitourinary chlamydia.
  • Same-day results not available:
    • Provide empiric treatment for urethritis.
    • Narrow antibiotics if culture results become available.
• Patients with urethritis secondary to an STI
  • Advise patients on preventing onward transmission of a bacterial STI.
  • Provide management of sexual partners.
  • Offer patients counseling on STI prevention, including HIV PrEP if appropriate.
  • Report notifiable diseases (e.g., chlamydia and gonorrhea).
• Ensure appropriate follow-up for urethritis; patients with persistent symptoms may require further testing.

Empiric treatment for urethritis ^[1]

• Treat patients for gonococcal urethritis if:
  • A presumptive diagnosis of gonococcal urethritis is made
  • Urethritis was confirmed by a method other than microscopy
  • They are symptomatic with multiple risk factors for STIs and there are concerns about poor follow-up
• Treat all other patients for nongonococcal urethritis.

Empiric treatment for gonococcal urethritis

• Ceftriaxone IM once ^[1]
• PLUS oral doxycycline ^[1]

Empiric treatment for nongonococcal urethritis

• Recommended: doxycycline ^[1]
• Alternative: azithromycin ^[1]
• Suspected trichomoniasis : metronidazole or tinidazole ^[1]

Follow-up for urethritis ^[1][6]

For all patients diagnosed with chlamydia or gonorrhea, repeat NAAT 3 months after completion of treatment. ^[1]

Persistent or refractory symptoms

• Assess for reexposure and nonadherence to treatment.
  • If either is identified, consider repeating the initial treatment regimen.
  • Otherwise, repeat diagnostics for urethritis.
• If urethritis is confirmed on repeat testing, obtain diagnostics for M. genitalium infection and/or trichomoniasis and treat if positive. ^[1]
• If workup is negative, consider:
  • Culture with antibiotic sensitivity testing
  • Referral to urology and/or infectious diseases
  • Differential diagnoses of urethritis
  • Noninfectious etiologies of urethritis

Most cases of persistent gonococcal urethritis are due to repeat infection rather than treatment failure. ^[6]

• Other genitourinary tract infections, e.g., cystitis, epididymitis, prostatitis, cervicitis, pelvic inflammatory disease
• Urethral stricture or stenosis
• Infertility
• Disseminated gonococcal infection
• Reactive arthritis

We list the most important complications. The selection is not exhaustive.

See “Prevention of STIs” and “Screening for STIs.”