How do I diagnose and treat urethritis in the absence of urethral discharge?

Diagnosing and Treating Urethritis Without Discharge

Treat empirically with ceftriaxone 250 mg IM once plus either azithromycin 1 g orally once or doxycycline 100 mg orally twice daily for 7 days while awaiting test results, as the absence of discharge does not exclude urethritis and diagnostic confirmation should guide definitive therapy. 1

Diagnostic Confirmation

Document urethritis objectively before treating, even without visible discharge:

• Gram stain of urethral secretions showing ≥5 white blood cells per oil immersion field is the preferred rapid diagnostic test with high sensitivity and specificity 2, 1
• First-void urine with positive leukocyte esterase test OR ≥10 white blood cells per high-power field on microscopy serves as an alternative when urethral swab is not feasible 2, 1, 3
• Urethral symptoms alone (dysuria, itching, discomfort) without objective findings are insufficient for diagnosis 2, 3

Critical Diagnostic Pitfall

Research demonstrates that polymorphonuclear leukocyte tests have low sensitivity (29-62%) for detecting Chlamydia trachomatis and Mycoplasma genitalium in patients without discharge 4. This means you cannot rely solely on negative microscopy to rule out infection when symptoms are present.

Microbiological Testing (Mandatory)

Order nucleic acid amplification testing (NAAT) on first-void urine or urethral swab for both N. gonorrhoeae and C. trachomatis in all cases 1, 5, 6:

• C. trachomatis causes 23-55% of nongonococcal urethritis cases 2, 5, 7
• N. gonorrhoeae accounts for approximately 11% of cases even without classic purulent discharge 4
• Mycoplasma genitalium is implicated in 17-33% of cases but specific testing is not routinely indicated unless treatment fails 2, 5, 4
• Ureaplasma urealyticum causes 20-40% of cases 2, 5
• Trichomonas vaginalis accounts for 2-5% of cases 2, 5

Up to 50% of nongonococcal urethritis cases remain idiopathic despite comprehensive testing 5, 7.

First-Line Empiric Treatment Algorithm

If diagnostic tools are unavailable or patient is unlikely to return for follow-up, treat immediately for both gonorrhea and chlamydia 2, 1:

Recommended Dual Therapy:

• Ceftriaxone 250 mg IM as single dose
• PLUS azithromycin 1 g orally as single dose 1
• OR doxycycline 100 mg orally twice daily for 7 days 2, 1

If Diagnostic Confirmation Available:

For confirmed nongonococcal urethritis (negative for gonorrhea):

• Azithromycin 1 g orally single dose 2
• OR doxycycline 100 mg orally twice daily for 7 days 2, 3

Alternative regimens if first-line options contraindicated:

• Erythromycin base 500 mg orally four times daily for 7 days 2
• Ofloxacin 300 mg orally twice daily for 7 days 2, 3
• Levofloxacin 500 mg orally once daily for 7 days 3

Treatment Selection Nuance

Azithromycin provides superior compliance with single-dose therapy but doxycycline may be preferred when Mycoplasma genitalium prevalence is high and macrolide resistance is a concern 1, 7. However, for empirical treatment without test results, both regimens achieve comparable 77-81% clinical cure rates 8.

Partner Management (Non-Negotiable)

All sexual partners within the preceding 60 days must be evaluated and treated with the same regimen, regardless of symptoms or test results 1, 3:

• Both patient and all partners must abstain from sexual intercourse for 7 days after single-dose therapy or until completion of multi-day regimens 1, 3
• Failure to treat partners is the leading cause of persistent or recurrent urethritis 2

Follow-Up Strategy

Instruct patients to return only if symptoms persist or recur after completing therapy 2, 1:

• Symptoms alone without objective signs (discharge, elevated WBCs) are insufficient for retreatment 2, 1
• Test of cure is not routinely recommended unless symptoms persist, reinfection is suspected, or compliance is questionable 3
• If test of cure is performed, wait at least 3 weeks after treatment completion 3, 7

Management of Persistent/Recurrent Urethritis

First confirm urethritis with microscopy and assess for reinfection or noncompliance 7:

• If doxycycline was initial therapy: give azithromycin 1.5 g distributed over 5 days plus metronidazole 400-500 mg twice daily for 5-7 days 7
• If azithromycin was initial therapy: give doxycycline 100 mg twice daily for 7 days plus metronidazole, OR moxifloxacin 400 mg once daily for 7-14 days 7
• Consider testing for Trichomonas vaginalis and HSV in nonresponsive cases 2, 5

Critical Complications to Prevent

Untreated urethritis leads to epididymitis, Reiter's syndrome, and transmission to female partners with risk of pelvic inflammatory disease 2, 1:

• All patients should receive syphilis serology and HIV counseling/testing at diagnosis 1
• Complications are particularly associated with C. trachomatis infection 2

Key Clinical Caveat

Defer treatment only if no objective signs of urethritis are present AND patient is reliable for follow-up 2. In this scenario, test for N. gonorrhoeae and C. trachomatis and treat only if positive. However, for high-risk patients (adolescents, multiple partners) who are unlikely to return, empiric treatment is mandatory even without documented urethritis 2.