What is the treatment for a patient with suspected urethritis?

Treatment of Suspected Urethritis

For patients with suspected urethritis, confirm the diagnosis with objective evidence (urethral discharge, Gram stain showing ≥5 WBCs per oil immersion field, positive leukocyte esterase test, or first-void urine with ≥10 WBCs per high-power field) before treating, then initiate empiric dual therapy with doxycycline 100 mg orally twice daily for 7 days PLUS ceftriaxone 250 mg intramuscularly as a single dose to cover both chlamydia and gonorrhea. 1, 2, 3

Diagnostic Confirmation Required Before Treatment

• Urethritis must be confirmed by at least one objective criterion: mucopurulent or purulent urethral discharge on examination, Gram stain of urethral secretions 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, 4, 2

• If none of these criteria are present, defer treatment and test for N. gonorrhoeae and C. trachomatis using nucleic acid amplification tests (NAATs), which are more sensitive than culture for detecting these pathogens 1, 4

• The only exception: Empiric treatment without documentation is acceptable for high-risk patients unlikely to return for follow-up (e.g., adolescents with multiple partners), and these patients must receive dual coverage for both gonorrhea and chlamydia 1, 5

First-Line Empiric Treatment Regimen

• Doxycycline 100 mg orally twice daily for 7 days is the preferred treatment for nongonococcal urethritis, covering C. trachomatis (the most common cause, accounting for 23-55% of NGU cases) and U. urealyticum 6, 5, 7, 8

• PLUS ceftriaxone 250 mg intramuscularly as a single dose to cover N. gonorrhoeae, as gonococcal and nongonococcal urethritis cannot be reliably distinguished by symptoms alone 2, 3

• Alternative to doxycycline: Azithromycin 1 gram orally as a single dose offers the advantage of directly observed therapy and ensures compliance, and is FDA-approved for urethritis due to C. trachomatis or N. gonorrhoeae 5, 9, 3

Important Caveat on Azithromycin

• Avoid azithromycin as routine first-line therapy without test of cure because it will select for macrolide-resistant M. genitalium strains in the population, which is increasingly recognized as a cause of 10-30% of NGU cases 8, 10

Pathogen-Specific Testing

• All patients with confirmed urethritis must be tested for both N. gonorrhoeae and C. trachomatis using NAATs, as both infections are reportable and a specific diagnosis improves treatment compliance and partner notification 6, 4, 10

• Consider testing for M. genitalium in areas where testing is available, particularly if symptoms persist after standard therapy, as this organism causes 10-30% of NGU and may require different treatment 8, 10

• Test for T. vaginalis if symptoms persist after initial treatment or if risk factors suggest protozoal infection (causes 2-5% of NGU) 6, 8

Management of Persistent or Recurrent Urethritis

• Re-confirm urethritis with microscopy showing objective evidence of inflammation before retreating 5, 8

• Rule out non-compliance and partner reinfection first, as these are the most common causes of treatment failure 8, 11

• If doxycycline was used initially: Treat with azithromycin 1 gram orally as a single dose PLUS metronidazole 2 gram orally as a single dose (or tinidazole 2 gram orally as a single dose) to cover T. vaginalis and anaerobes 5, 8

• If azithromycin was used initially: Treat with doxycycline 100 mg orally twice daily for 7 days PLUS metronidazole, OR consider moxifloxacin 400 mg orally once daily for 7-14 days if M. genitalium is suspected or confirmed 5, 8

• For confirmed M. genitalium with macrolide resistance: Moxifloxacin 400 mg orally once daily for 7-14 days is indicated 8

Critical Partner Management

• All sexual partners within the preceding 60 days must be evaluated and treated with the same regimen effective against chlamydia, regardless of whether a specific pathogen is identified in the index patient 1, 5, 4

• Both patient and partners must abstain from sexual intercourse until 7 days after therapy is initiated AND symptoms have completely resolved 5, 2

• Expedited partner treatment (giving patients prescriptions for partners who have not been examined) is advocated by the CDC and approved in many states to improve partner treatment rates 3

Follow-Up and Retesting

• Test of cure is NOT recommended for asymptomatic patients who received recommended treatment and completed therapy 5

• Patients should return for evaluation if symptoms persist or recur after completing therapy 1, 5

• Repeat testing 3-6 months after treatment is recommended due to high reinfection rates, with shared decision-making about future screening intervals 1, 5, 2

• Do not retest earlier than 3 weeks after treatment initiation because NAATs can produce false-positive results from detecting non-viable organisms during this period 8, 2

Common Pitfalls to Avoid

• Never treat based on symptoms alone without objective evidence of urethritis unless the patient meets high-risk criteria for empiric treatment 1

• Do not rely on semen analysis to diagnose urethritis—leukocytospermia is irrelevant for urethritis diagnosis and semen analysis evaluates fertility or prostatitis, not urethral inflammation 5

• Always test for syphilis in patients with sexually transmitted urethritis, as antimicrobial agents used for short periods may mask or delay symptoms of incubating syphilis 6, 9

• Ensure adequate fluid intake with doxycycline to reduce risk of esophageal irritation and ulceration; if gastric irritation occurs, give with food or milk 7