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), then treat empirically 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 while awaiting nucleic acid amplification test results. 1, 2, 3
Diagnostic Confirmation Before Treatment
Objective evidence required: Document at least one of the following before initiating treatment: 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, 2, 4
Gram stain is the gold standard rapid test: If available, perform Gram stain of urethral secretions—it simultaneously confirms urethritis (≥5 WBCs per oil immersion field) and identifies gonococcal infection if intracellular Gram-negative diplococci are present 4, 5
Always obtain NAAT testing: All patients with confirmed urethritis must be tested for both Neisseria gonorrhoeae and Chlamydia trachomatis using nucleic acid amplification tests, which are more sensitive than culture for C. trachomatis 1, 4, 5
Empiric Treatment Regimen
First-line dual therapy: Treat with doxycycline 100 mg orally twice daily for 7 days (highly effective for chlamydial urethritis) PLUS coverage for gonorrhea with ceftriaxone 250 mg intramuscularly 2, 6, 3, 7
Alternative for chlamydia coverage: Azithromycin 1 gram orally as a single dose can replace doxycycline, with the advantage of directly observed single-dose therapy ensuring compliance, though it is particularly important for Mycoplasma genitalium coverage 2, 8, 5
Initiate treatment before test results: Begin empiric therapy at the first visit if urethritis is confirmed by objective criteria, without waiting for NAAT results 9, 5, 3
When to Defer Treatment
No objective evidence: If none of the diagnostic criteria are present, defer treatment and perform NAAT testing for N. gonorrhoeae and C. trachomatis, then follow closely for results 1, 4
Exception for high-risk patients: Treat empirically without documentation only for patients at high risk for infection (adolescents with multiple partners) who are unlikely to return for follow-up, and these patients must receive dual coverage for both gonorrhea and chlamydia 1, 2
Management of Persistent or Recurrent Urethritis
Re-confirm urethritis objectively: Document urethritis again with microscopy or other objective criteria, rule out non-compliance with initial treatment, and assess for partner reinfection 2, 5
Test for additional pathogens: Obtain testing for Trichomonas vaginalis and consider tetracycline-resistant Ureaplasma urealyticum or Mycoplasma genitalium 2, 5
Second-line treatment: If doxycycline was used initially, treat with azithromycin 1 gram orally as a single dose (or azithromycin 500 mg on day 1, then 250 mg daily for 4 more days) PLUS metronidazole 2 gram orally as a single dose 2, 5
Consider moxifloxacin: For macrolide-resistant M. genitalium or treatment failures, use moxifloxacin 400 mg orally once daily for 7-14 days 2, 5
Partner Management and Prevention
Mandatory partner treatment: 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, 2, 4
Sexual abstinence required: Both patient and partners must abstain from sexual intercourse for 7 days after therapy is initiated and until symptoms have completely resolved 2, 3
Expedited partner treatment: Consider providing prescriptions for partners who have not been examined, as this approach is advocated by the CDC and approved in many states 7
Follow-Up Strategy
Return if symptoms persist: Patients should return for re-evaluation if symptoms persist or recur after completion of therapy 1, 2
No routine test-of-cure: Test-of-cure is not recommended for asymptomatic patients who received recommended treatment and completed therapy 2, 5
Reinfection screening: Consider repeat testing 3-6 months after treatment due to high reinfection rates, particularly in adolescents and young adults 1, 2, 3
Avoid early repeat testing: Do not perform repeat testing less than 3 weeks after treatment completion, as false-positive NAAT results are possible during this period due to detection of non-viable organisms 3
Common Pitfalls to Avoid
Never treat on symptoms alone: Do not initiate treatment based solely on symptoms without objective evidence of urethritis unless the patient meets high-risk criteria for empiric treatment 1
Do not rely on urine microscopy alone: Ensure NAAT testing is performed rather than relying solely on urine microscopy, as NAATs are significantly more sensitive for detecting C. trachomatis and N. gonorrhoeae 1
Avoid azithromycin monotherapy without follow-up: Using azithromycin as first-line treatment without test-of-cure for M. genitalium and subsequent moxifloxacin treatment of macrolide-resistant strains will select and increase macrolide-resistant strains in the population 5
Screen for syphilis: All patients with sexually transmitted urethritis should have serologic testing for syphilis at the time of diagnosis, as antimicrobial agents used for urethritis may mask or delay symptoms of incubating syphilis 9, 8