What is the recommended treatment for a patient with urethritis, potentially caused by a bacterial infection such as gonorrhea or chlamydia?

Treatment of Urethritis

For acute urethritis, treat empirically with dual therapy: Ceftriaxone 250-500 mg IM single dose PLUS Doxycycline 100 mg orally twice daily for 7 days to cover both gonorrhea and chlamydia before culture results are available. 1

Initial Diagnostic Confirmation

Before initiating treatment, document objective evidence of urethritis using at least one of the following criteria:

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

All patients must be tested for both Neisseria gonorrhoeae and Chlamydia trachomatis using nucleic acid amplification tests (NAATs), which are more sensitive than culture for chlamydia. 2, 1 Testing for both pathogens improves partner notification and treatment compliance. 3, 2

First-Line Treatment Regimen

Dual Therapy (Covers Both Gonorrhea and Chlamydia)

• Ceftriaxone 250-500 mg IM single dose (for gonococcal coverage) 3, 1
• PLUS Doxycycline 100 mg orally twice daily for 7 days (for chlamydial and nongonococcal urethritis coverage) 4, 1, 5

This dual approach is essential because co-infection is common, and delaying treatment increases risk of complications and ongoing transmission. 1 Most sexually transmitted urethritis in men under 35 years is caused by C. trachomatis or N. gonorrhoeae. 1, 6

Alternative Regimens for Chlamydial/Nongonococcal Component

If doxycycline cannot be used, the following alternatives are acceptable for the chlamydial component:

• Azithromycin 1 g orally as a single dose 1, 7
• Erythromycin base 500 mg orally four times daily for 7 days 4
• Erythromycin ethylsuccinate 800 mg orally four times daily for 7 days 4
• Ofloxacin 300 mg orally twice daily for 7 days 4
• Levofloxacin 500 mg orally once daily for 7 days 4

Critical Management Points

Sexual Activity Restrictions

• Patients must abstain from sexual intercourse for 7 days after treatment initiation AND until symptoms resolve AND partners are adequately treated. 3, 1

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, 3, 1
• If the last sexual contact was more than 60 days before symptom onset, treat the most recent sexual partner. 3

Follow-Up

• Patients should return for evaluation only if symptoms persist or recur after completing therapy. 4
• Symptoms alone, without documentation of signs or laboratory evidence of urethral inflammation, are NOT sufficient basis for re-treatment. 4

Important Warnings and Contraindications

What NOT to Do for Gonococcal Urethritis

• Do NOT use oral cephalosporins (like cefixime) for pharyngeal gonorrhea—they have unacceptably low cure rates (approximately 57%). 3
• Do NOT use azithromycin monotherapy (even at 2 g dose) due to cost, gastrointestinal side effects, and concerns about rapid emergence of resistance. 3
• Do NOT use fluoroquinolones (ciprofloxacin, ofloxacin) for gonorrhea due to widespread resistance, particularly in men who have sex with men and patients with recent foreign travel. 3
• Do NOT use penicillins, tetracyclines, or macrolides as monotherapy for gonorrhea—N. gonorrhoeae in the United States is not adequately susceptible to these agents. 3

Pregnancy Considerations

• Pregnant women should receive ceftriaxone 500 mg IM single dose for gonococcal infection. 3
• Doxycycline and fluoroquinolones are absolutely contraindicated in pregnancy. 3

Recurrent or Persistent Urethritis

If symptoms persist after appropriate treatment:

• Re-treat with the initial regimen if the patient did not comply with treatment or was re-exposed to an untreated sex partner. 4
• If the patient was compliant and re-exposure can be excluded, perform culture of an intra-urethral swab and first-void urine for Trichomonas vaginalis. 4
• Some cases of recurrent urethritis following doxycycline may be caused by tetracycline-resistant Ureaplasma urealyticum. 4

Recommended Regimen for Persistent/Recurrent Cases

• Metronidazole 2 g orally in a single dose 4
• PLUS Erythromycin base 500 mg orally four times daily for 7 days 4
• OR Erythromycin ethylsuccinate 800 mg orally four times daily for 7 days 4

Special Populations

HIV-Infected Patients

• HIV-infected patients should receive the same treatment regimen as HIV-negative patients—no modification is needed. 4, 3, 1
• Gonococcal urethritis, chlamydial urethritis, and nongonococcal urethritis may facilitate HIV transmission. 4

Additional Considerations

• All patients with sexually-transmitted urethritis should have serologic testing for syphilis and HIV performed at the time of diagnosis. 1, 7
• Antimicrobial agents used in high doses for short periods may mask or delay symptoms of incubating syphilis. 7
• Administer adequate fluids with doxycycline capsules/tablets to reduce risk of esophageal irritation and ulceration. 5
• If gastric irritation occurs with doxycycline, give with food or milk—absorption is not markedly influenced by simultaneous food ingestion. 5