Treatment of Urethritis with Symptoms but Absent White Blood Cells on First-Void Urine
When symptoms of urethritis are present but white blood cells are absent on first-void urine microscopy, treatment should generally be deferred and the patient should be tested for N. gonorrhoeae and C. trachomatis with close follow-up, unless the patient is at high risk for infection and unlikely to return for evaluation—in which case empiric treatment for both gonorrhea and chlamydia is recommended. 1
Diagnostic Confirmation Required
The absence of white blood cells on first-void urine means urethritis has not been objectively documented. According to CDC guidelines, urethritis should be confirmed by at least one of the following criteria before initiating treatment: 1
- Mucopurulent or purulent urethral discharge (visible on examination) 1
- Gram stain of urethral secretions showing ≥5 WBCs per oil immersion field 1
- Positive leukocyte esterase test on first-void urine 1
- Microscopic examination of first-void urine demonstrating ≥10 WBCs per high-power field 1
If none of these criteria are present, treatment should be deferred. 1 The patient should be tested for N. gonorrhoeae and C. trachomatis using nucleic acid amplification tests (which can be performed on first-void urine and are highly sensitive) and followed closely. 1
When to Treat Empirically Despite Absent WBCs
Empiric treatment without documentation of urethritis is recommended only for patients at high risk for infection who are unlikely to return for follow-up evaluation (such as adolescents with multiple partners). 1, 2, 3 These patients should receive treatment covering both gonorrhea and chlamydia. 1
Recommended Empiric Regimen for High-Risk Patients:
- Azithromycin 1g orally as a single dose 1, 4, 2, 3, 5
- Plus treatment for gonorrhea (typically ceftriaxone) if gonococcal infection cannot be ruled out 7, 8
Azithromycin has the advantage of single-dose administration, ensuring compliance and allowing directly observed therapy, and is particularly effective against Mycoplasma genitalium. 4, 3 Doxycycline requires patient compliance with a 7-day regimen but is highly effective for chlamydial urethritis. 4, 3, 6
If Testing Returns Positive
If nucleic acid amplification testing demonstrates infection with either N. gonorrhoeae or C. trachomatis, appropriate pathogen-directed treatment should be given and sexual partners referred for evaluation and treatment. 1
Partner Management
All sexual partners within the preceding 60 days must be evaluated and treated, and should receive treatment effective against chlamydia regardless of whether a specific pathogen is identified in the index patient. 4, 2, 3 Both the patient and partners should abstain from sexual intercourse until 7 days after therapy is initiated and symptoms have resolved. 4, 3
Common Pitfalls to Avoid
- Do not 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 or leukocytospermia to diagnose urethritis—proper urethral testing with first-void urine or urethral secretions is required 4
- Ensure nucleic acid amplification testing is performed rather than relying solely on urine microscopy, as these tests are more sensitive for detecting C. trachomatis and N. gonorrhoeae 1
- Consider that symptoms without objective findings may represent non-infectious causes or resolved infection 1
Follow-Up Considerations
Patients should return for evaluation if symptoms persist or recur after completion of therapy. 1, 3 Symptoms alone, without documentation of signs or laboratory evidence of urethral inflammation, are not sufficient basis for re-treatment. 1 Consider repeat testing 3-6 months after treatment due to high reinfection rates. 4, 3