Treatment of Urethritis with Cefixime and Doxycycline
The proposed regimen of cefixime 400mg once daily plus doxycycline 100mg twice daily for 7 days is NOT the recommended first-line treatment for urethritis, but it may be appropriate in specific clinical scenarios where gonococcal infection is suspected or confirmed alongside chlamydial/nongonococcal urethritis.
Why This Regimen Deviates from Guidelines
The standard CDC-recommended treatment for nongonococcal urethritis (NGU) is either azithromycin 1g as a single dose OR doxycycline 100mg twice daily for 7 days—without routinely adding cefixime 1. Your proposed regimen adds cefixime, which is specifically indicated for gonococcal infections, not routine NGU 2.
When Your Regimen Makes Clinical Sense
If gonococcal urethritis is suspected or confirmed, dual therapy covering both gonorrhea and chlamydia is essential 3, 4:
- For documented or suspected gonorrhea: The doxycycline component (100mg twice daily for 7 days) appropriately covers chlamydial co-infection and NGU 1, 5
- However, cefixime 400mg is suboptimal for gonorrhea: Current guidelines strongly prefer ceftriaxone 1g IM/IV as a single dose over oral cefixime due to rising resistance concerns 3
- The FDA label confirms cefixime 400mg as a single dose (not daily) for uncomplicated gonococcal urethritis 2
The Correct Approach Based on Clinical Scenario
For Nongonococcal Urethritis (NGU) Only:
Choose ONE of these first-line options 1:
- Azithromycin 1g orally as a single dose (best for compliance) 1
- Doxycycline 100mg orally twice daily for 7 days (equally effective for chlamydia) 1, 5
For Suspected or Confirmed Gonococcal Urethritis:
The optimal regimen is 3:
- Ceftriaxone 1g IM or IV as a single dose
- PLUS azithromycin 1g orally as a single dose
If ceftriaxone is unavailable and you must use oral therapy:
Critical Pitfalls to Avoid
Dosing Error with Cefixime
The FDA label specifies cefixime 400mg as a single dose for gonococcal urethritis, not once daily for multiple days 2. Prescribing it "once a day" for 7 days is incorrect dosing and wastes medication.
Missing the Diagnosis
Before empiric treatment, confirm urethritis with at least one criterion 1, 3:
- Visible urethral discharge
- Positive leukocyte esterase on first-void urine
- ≥10 WBCs per high-power field in urine sediment
All patients should have NAAT testing for both N. gonorrhoeae and C. trachomatis before or at the time of treatment 1, 3.
Resistance Considerations
- Cefixime has documented treatment failures for gonorrhea compared to ceftriaxone 3
- Ciprofloxacin and other fluoroquinolones are inadequate for chlamydial urethritis, with relapse rates exceeding 50% 6
- Some recurrent NGU cases after doxycycline may be due to tetracycline-resistant U. urealyticum 1
Additional Management Essentials
Partner Management
All sexual partners within the preceding 60 days must be evaluated and treated 1. Expedited partner therapy (providing prescriptions without examination) is endorsed by the CDC and legal in many jurisdictions 4.
Abstinence Period
Patients must abstain from sexual intercourse until 7 days after therapy initiation AND both patient and partners complete treatment 1.
Testing for Co-infections
All patients with newly diagnosed STIs require testing for syphilis and HIV 3.
Follow-Up
Return visits are only needed if symptoms persist or recur after completing therapy 1. Symptoms alone without objective urethritis signs do not warrant re-treatment 1.
Bottom Line
If this is NGU without gonorrhea: Use doxycycline 100mg twice daily for 7 days alone (or azithromycin 1g single dose) and omit the cefixime entirely 1.
If gonorrhea is confirmed or highly suspected: Use ceftriaxone 1g IM once plus azithromycin 1g orally once as the superior regimen 3. Only use cefixime 400mg as a single dose (not daily) if ceftriaxone is truly unavailable, and combine it with doxycycline 100mg twice daily for 7 days 2, 5.