What is the recommended empirical evaluation and treatment for acute urethritis?

Empirical Evaluation and Treatment of Acute Urethritis

For patients with suspected acute urethritis, immediately treat empirically with ceftriaxone 250 mg intramuscularly once PLUS doxycycline 100 mg orally twice daily for 7 days (or azithromycin 1 g orally as a single dose) while awaiting test results, especially if the patient is unlikely to return for follow-up. 1, 2

Diagnostic Confirmation Before Treatment (When Feasible)

Document urethritis objectively before initiating therapy using at least one of the following criteria:

• Mucopurulent or purulent urethral discharge visible on examination 1, 2
• Gram stain of urethral secretions showing ≥5 white blood cells per oil-immersion field 1, 2
• Positive leukocyte esterase test on first-void urine 1, 2
• Microscopic examination of first-void urine showing ≥10 white blood cells per high-power field 1, 2

Critical caveat: Symptoms alone (dysuria, urethral discomfort, itching) without objective laboratory findings are insufficient to diagnose urethritis and do not justify antimicrobial therapy. 1, 2

Exception: High-risk patients (adolescents with multiple partners, those unlikely to return) should receive empiric treatment even without documented urethritis. 1, 2

Rapid Diagnostic Testing

Gram stain is the preferred point-of-care test because it simultaneously confirms urethritis AND differentiates gonococcal from non-gonococcal etiology:

• Intracellular gram-negative diplococci indicate gonococcal urethritis (specificity >99%, sensitivity >95%) 2
• ≥5 leukocytes per oil-immersion field without diplococci suggest non-gonococcal urethritis 2

Mandatory Microbiological Testing

All patients with confirmed or suspected urethritis must be tested for both Neisseria gonorrhoeae and Chlamydia trachomatis using nucleic acid amplification tests (NAATs) on first-void urine or urethral swab. 1, 2

Key pathogen prevalence in non-gonococcal urethritis:

• C. trachomatis: 23-55% of cases 1, 3
• Ureaplasma urealyticum: 20-40% 1
• Mycoplasma genitalium: 17-33% 1
• Trichomonas vaginalis: 2-5% 1

First-Line Empiric Treatment Algorithm

When Gram Stain Shows Diplococci (Gonococcal Urethritis)

Treat for both gonorrhea and chlamydia simultaneously:

• Ceftriaxone 250 mg intramuscularly once PLUS
• Either azithromycin 1 g orally once OR doxycycline 100 mg orally twice daily for 7 days 4, 1, 2

When Gram Stain Shows Leukocytes Without Diplococci (Non-Gonococcal Urethritis)

Choose one of the following CDC-recommended regimens:

• Azithromycin 1 g orally as a single dose 4, 1, 3, 5
• OR Doxycycline 100 mg orally twice daily for 7 days 4, 1, 3

Azithromycin is preferred for single-dose compliance and superior activity against Mycoplasma genitalium. 1, 2

When Diagnostic Tools Are Unavailable or Patient Is High-Risk

Provide dual therapy covering both gonorrhea and chlamydia:

• Ceftriaxone 250 mg intramuscularly once PLUS
• Doxycycline 100 mg orally twice daily for 7 days (or azithromycin 1 g orally once) 4, 1, 2

Dispense medications on-site with the first dose directly observed to maximize adherence. 2

Alternative Regimens (When First-Line Agents Contraindicated)

For non-gonococcal urethritis when macrolides or tetracyclines cannot be used:

• Erythromycin base 500 mg orally four times daily for 7 days 4, 2
• OR Ofloxacin 300 mg orally twice daily for 7 days 4, 2
• OR Levofloxacin 500 mg orally once daily for 7 days 4, 2

Critical Partner Management

All sexual partners within the preceding 60 days must be evaluated and treated with the same regimen as the index patient, regardless of symptoms or test results. 4, 1, 3, 2

Failure to treat partners is the leading cause of persistent or recurrent urethritis. 1

Both patient and partners must abstain from sexual intercourse for 7 days after treatment initiation AND until all symptoms have completely resolved. 4, 1, 3, 2

Follow-Up Strategy

Instruct patients to return for evaluation ONLY if symptoms persist or recur after completing therapy. 4, 1, 3

Symptoms alone without objective signs (discharge, elevated white blood cell counts) are insufficient to justify retreatment. 4, 1, 3

For persistent or recurrent urethritis:

• Re-document urethritis using the same objective criteria before prescribing additional antibiotics 1, 3
• Consider reinfection or non-compliance first 3
• Test for Trichomonas vaginalis and herpes simplex virus if initial therapy fails 1, 3

If the patient was compliant and re-exposure is excluded, treat with:

• Metronidazole 2 g orally once PLUS erythromycin base 500 mg orally four times daily for 7 days 4

Prevention of Complications

Untreated urethritis, especially due to C. trachomatis, can lead to:

• Epididymitis 1, 2
• Reactive arthritis (Reiter syndrome) 1, 2
• Transmission to female partners resulting in pelvic inflammatory disease 1, 2

All patients with sexually transmitted urethritis should receive serologic testing for syphilis and HIV counseling/testing at diagnosis. 1, 2

Common Pitfalls to Avoid

Do not prescribe antibiotics for persistent symptoms without re-documenting objective evidence of urethral inflammation (≥5 leukocytes per high-power field). 3

Do not defer treatment in high-risk individuals even when objective criteria are absent, because they are unlikely to return for follow-up. 1, 2

Remember that ceftriaxone has no significant effect on chlamydial infection, so dual therapy is mandatory for gonococcal urethritis. 6