What is the recommended empiric treatment, testing, partner management, and follow‑up for acute honeymoon urethritis acquired after recent unprotected intercourse?

Management of Honeymoon Urethritis

For acute urethritis after recent unprotected intercourse, initiate empiric dual therapy immediately with ceftriaxone 250 mg IM single dose plus doxycycline 100 mg orally twice daily for 7 days to cover both gonorrhea and chlamydia before test results are available. 1

Empiric Treatment Rationale

Dual coverage is mandatory because urethritis is frequently accompanied by asymptomatic co-infection with both N. gonorrhoeae and C. trachomatis, and treating gonorrhea alone is inadequate. 1 The CDC explicitly recommends empiric therapy before culture results to achieve microbiologic cure, prevent transmission, and reduce complications such as epididymitis. 1

First-Line Antibiotic Regimen

• Ceftriaxone 250-500 mg intramuscularly as a single dose covers N. gonorrhoeae 1
• Doxycycline 100 mg orally twice daily for 7 days covers C. trachomatis and M. genitalium 2, 1

Alternative Chlamydia Coverage

• Azithromycin 1 g orally as a single dose may substitute for doxycycline when adherence to a 7-day course is unlikely 2, 1
• Azithromycin provides superior activity against Mycoplasma genitalium (which causes ~13% of non-gonococcal urethritis) and allows directly observed therapy 1
• Dispense medications on-site and directly observe the first dose to maximize compliance 1

Regimens to Avoid

• Fluoroquinolones (ciprofloxacin, levofloxacin, ofloxacin) should not be used for gonorrhea due to widespread resistance 1
• Azithromycin 1 g alone is insufficiently effective against gonorrhea and must not be used as monotherapy 1

Diagnostic Testing

Perform nucleic acid amplification tests (NAATs) for both N. gonorrhoeae and C. trachomatis on first-void urine or urethral swab as NAATs are more sensitive than culture. 1, 3

Confirmation of Urethritis

Document urethritis using at least one of the following criteria before treatment (though empiric therapy should not be delayed in high-risk patients unlikely to return): 2

• Mucopurulent or purulent urethral discharge
• Gram stain of urethral secretions showing ≥5 WBCs per oil immersion field
• Positive leukocyte esterase test on first-void urine
• Microscopic examination of first-void urine showing ≥10 WBCs per high-power field

Comprehensive STI Screening

Screen all patients with urethritis for HIV and syphilis as part of a comprehensive STI evaluation. 1

Partner Management

All sexual partners within the preceding 60 days must be evaluated and treated empirically with the same dual-therapy regimen (ceftriaxone plus doxycycline or azithromycin) before test results are available. 1 Partners should receive treatment for both gonorrhea and chlamydia regardless of the pathogen identified in the index case. 1, 4

Sexual Abstinence Requirements

• Patients must abstain from sexual intercourse for at least 7 days after therapy initiation and until all symptoms have resolved 2, 1
• Partners must also complete treatment before resuming sexual activity 4

Follow-Up

Patients should return for evaluation only if symptoms persist or recur after completing therapy. 2, 1 Routine test-of-cure is not required for asymptomatic patients who received the recommended dual regimen. 1

Management of Persistent Symptoms

If symptoms persist after initial therapy: 1, 4

• Re-confirm objective signs of urethritis before retreatment (symptoms alone without documentation of urethral inflammation are insufficient for re-treatment) 2
• Rule out non-compliance or partner reinfection
• Test for Trichomonas vaginalis using an intra-urethral swab or first-void urine 1
• Consider tetracycline-resistant Ureaplasma urealyticum as a possible cause 1

Reinfection Screening

Consider repeat testing 3-6 months after treatment due to high reinfection rates in this population. 4

Critical Pitfalls to Avoid

• Do not treat for gonorrhea alone without chlamydia coverage, as co-infection is common 1
• Do not delay treatment waiting for test results in patients with confirmed urethritis or high-risk patients unlikely to return 2, 1
• Do not forget to treat partners empirically before their test results are available 1
• Do not use fluoroquinolones for gonorrhea coverage due to resistance 1