What are the diagnostic and treatment approaches for urethritis?

Urethritis Diagnosis and Treatment

Diagnostic Criteria

Urethritis must be confirmed by objective evidence before treatment using any of the following: mucopurulent or purulent urethral discharge, Gram stain showing ≥5 WBCs per oil immersion field, positive leukocyte esterase test on first-void urine, or microscopic examination of first-void urine demonstrating ≥10 WBCs per high power field. 1, 2, 3

Preferred Diagnostic Approach

• Gram stain of urethral secretions is the preferred rapid diagnostic test because it simultaneously confirms urethritis (≥5 WBCs per oil immersion field) and identifies gonococcal infection if WBCs contain intracellular Gram-negative diplococci, with superior sensitivity and specificity compared to other rapid tests 1, 2

• First-void urine testing via leukocyte esterase test (positive result) or microscopic examination (≥10 WBCs per high power field) serves as an alternative when Gram stain is unavailable 1, 2, 4

• Visual inspection for mucopurulent or purulent discharge alone is sufficient to confirm urethritis 1, 2

Pathogen Testing

All patients with confirmed urethritis must be tested for both Neisseria gonorrhoeae and Chlamydia trachomatis using nucleic acid amplification tests (NAATs), which are more sensitive than culture for C. trachomatis. 2, 3, 4

• Testing for specific pathogens is strongly recommended because it improves partner notification, enhances treatment compliance, and allows for appropriate targeted therapy 1, 2

• C. trachomatis causes 15-55% of nongonococcal urethritis cases and is the most common identifiable pathogen 3, 4

Treatment Recommendations

First-Line Empiric Therapy

Initiate treatment immediately upon diagnosis with either azithromycin 1g orally as a single dose OR doxycycline 100mg orally twice daily for 7 days. 1, 3, 5

• Azithromycin has the advantage of single-dose administration ensuring compliance and allowing directly observed therapy, and is particularly effective against Mycoplasma genitalium. 1, 3, 6

• Doxycycline is highly effective for chlamydial urethritis but requires 7-day compliance 1, 3

• Both regimens achieve comparable clinical cure rates of 77-81% for nongonococcal urethritis 6

Alternative Regimens (if first-line options cannot be used)

• Erythromycin base 500mg orally four times daily for 7 days 1

• Erythromycin ethylsuccinate 800mg orally four times daily for 7 days 1

• Ofloxacin 300mg orally twice daily for 7 days 1

• Levofloxacin 500mg orally once daily for 7 days 1

When to Defer Treatment

• If none of the objective diagnostic criteria are present, defer treatment and test for N. gonorrhoeae and C. trachomatis, then follow closely for results. 1, 2

• Treat based on test results only if infection is confirmed 1

Empiric Treatment Without Documentation

• Empiric treatment without confirming urethritis is acceptable ONLY for high-risk patients unlikely to return for follow-up, and these patients should receive treatment covering both gonorrhea and chlamydia. 1, 2, 3

• This approach prevents loss to follow-up in vulnerable populations 1

Partner Management

All sexual partners within the preceding 60 days must be evaluated and treated, and partners should receive treatment effective against chlamydia regardless of whether a specific pathogen is identified in the index patient. 1, 2, 3

• Both patient and partners must abstain from sexual intercourse until 7 days after therapy is initiated and symptoms have resolved 1, 3

• A specific pathogen diagnosis facilitates partner notification and improves treatment compliance 1, 2

Management of Persistent or Recurrent Urethritis

Re-evaluation Algorithm

• Confirm objective signs of urethritis are present before initiating further antimicrobial therapy—symptoms alone without documentation of urethral inflammation are not sufficient basis for re-treatment. 1, 3

• First, rule out non-compliance with initial treatment or re-exposure to untreated partner 1, 3

• If compliance and partner treatment are confirmed, test for Trichomonas vaginalis via culture of intraurethral swab specimen 1

Treatment for Confirmed Persistent/Recurrent Urethritis

Metronidazole 2g orally as a single dose or tinidazole 2g orally as a single dose, PLUS azithromycin 1g orally as a single dose (if not used for initial episode). 1, 3, 7

• This regimen targets T. vaginalis and tetracycline-resistant Ureaplasma urealyticum 1, 7

• Consider emerging pathogens including Haemophilus influenzae, Corynebacterium, Ureaplasma, and Staphylococcus haemolyticus in refractory cases 8

Follow-Up

• Patients should return for evaluation if symptoms persist or recur after treatment completion 1, 3

• Test-of-cure is not recommended for asymptomatic patients who received recommended treatment. 3, 7

• Consider repeat testing 3-6 months after treatment due to high reinfection rates 3, 7

• Persistence of symptoms beyond 3 months should prompt evaluation for chronic prostatitis/chronic pelvic pain syndrome 1

Additional Testing

• All patients diagnosed with a new sexually transmitted disease should receive testing for other STDs, including syphilis and HIV 1, 3

• This is critical because antimicrobial agents used for urethritis may mask or delay symptoms of incubating syphilis 5

Common Pitfalls

• Do not treat based on symptoms alone without objective evidence of urethritis—this leads to antibiotic overuse and misuse 1, 3

• Do not extend antimicrobial duration for persistent symptoms without documented urethritis—the value of this approach has not been demonstrated 1

• Urologic examinations in recurrent cases usually do not reveal a specific etiology and are not routinely indicated 1

• Semen analysis showing no leukocytospermia is irrelevant for diagnosing urethritis—proper urethral testing must be performed 7