What is the most appropriate treatment for a patient with a 2-day history of dysuria and urethral discharge after recent sexual activity with a new partner?

Treatment of Urethritis with Dysuria and Urethral Discharge

This patient should be treated empirically with ceftriaxone 125 mg IM in a single dose PLUS azithromycin 1 g orally in a single dose (or doxycycline 100 mg orally twice daily for 7 days). The correct answer is both B (Azithromycin) and C (Ceftriaxone) used together.

Rationale for Dual Therapy

• Coinfection with Chlamydia trachomatis and Neisseria gonorrhoeae is extremely common in patients presenting with urethritis, particularly in those with recent sexual exposure to a new partner 1, 2

• The clinical presentation of dysuria and urethral discharge after recent sexual activity with a new partner represents a high-risk scenario requiring empiric treatment for both pathogens before test results are available 1, 3

• Treating only one organism when both are present leads to persistent symptoms, ongoing transmission to partners, and potential complications 2, 3

Recommended Treatment Regimen

For gonorrhea coverage:

• Ceftriaxone 125 mg IM in a single dose 1, 2

PLUS treatment for chlamydia:

• Azithromycin 1 g orally in a single dose 1
• OR Doxycycline 100 mg orally twice daily for 7 days 1

Why Single-Agent Therapy Is Inadequate

• Azithromycin alone (Option B) is insufficient because it does not reliably treat gonorrhea at the 1 g dose, with cure rates of only 93% 1

• Ceftriaxone alone (Option C) leaves chlamydial infection untreated, which is present in a substantial proportion of patients with urethritis 1, 2

• Gentamicin (Option A) is not a standard treatment for urethritis and is only considered for specific conditions like donovanosis with refractory lesions 4

• Nitrofurantoin (Option D) is a urinary tract antiseptic with no role in treating sexually transmitted urethritis 1

Clinical Approach

Immediate empiric treatment is indicated when:

• Patient has confirmed urethritis (discharge visible, or ≥10 WBCs per high-power field in first-void urine, or positive leukocyte esterase) 3, 5
• Patient is at high risk for infection (new sexual partner, recent sexual activity) 1
• Patient is unlikely to return for follow-up 1

Testing should still be performed:

• Nucleic acid amplification tests (NAATs) for both N. gonorrhoeae and C. trachomatis should be obtained even when treating empirically 1, 5
• This confirms the diagnosis, guides partner notification, and documents antimicrobial susceptibility patterns 1

Advantages of the Recommended Regimen

• Single-dose azithromycin offers superior compliance compared to 7-day doxycycline regimens, with compliance rates for multi-day regimens as low as 63.4% 1, 6

• Directly observed therapy is possible when medication is provided and administered in the clinic 1

• Ceftriaxone provides reliable coverage for gonorrhea including pharyngeal infections, which are more difficult to eradicate 1

Critical Partner Management

• All sexual partners from the preceding 60 days must be evaluated and treated for both N. gonorrhoeae and C. trachomatis 1, 2

• If the patient's last sexual contact was >60 days before symptom onset, the most recent partner should still be treated 1, 2

• Patient-delivered partner therapy (providing prescriptions or medications for partners) is an acceptable alternative when partner evaluation cannot be ensured 1

• Sexual abstinence is mandatory until 7 days after therapy initiation and until both patient and partners are asymptomatic 1, 5

Follow-Up Considerations

• Test of cure is not routinely needed for patients treated with recommended regimens who become asymptomatic 1

• Repeat testing should occur at 3 months due to high reinfection rates, not to assess treatment failure 1, 2, 5

• Persistent symptoms warrant re-evaluation with culture and antimicrobial susceptibility testing, as this suggests reinfection or infection with resistant organisms 1

Common Pitfalls to Avoid

• Do not delay treatment waiting for test results in symptomatic patients at high risk for infection 1, 3

• Do not use azithromycin monotherapy for gonorrhea due to resistance concerns and suboptimal efficacy 1, 2

• Do not forget to screen for syphilis and HIV in all patients with sexually transmitted urethritis 1, 7

• Do not assume treatment failure when symptoms persist—most cases represent reinfection from untreated partners rather than antimicrobial resistance 1, 2