Initial Treatment for Urethral Inflammation with Dysuria and Discharge
Initiate empiric dual therapy immediately with 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
Why Dual Coverage is Mandatory
- Urethritis is most commonly caused by Neisseria gonorrhoeae or Chlamydia trachomatis, and co-infection is frequent, making single-agent therapy inadequate 1, 2, 3
- The CDC explicitly recommends empiric therapy before culture results because treatment achieves microbiologic cure, symptom improvement, prevents transmission, and decreases complications such as epididymitis 1
- Delaying treatment until culture results increases risk of complications and ongoing transmission 1
First-Line Treatment Regimen
Ceftriaxone component (for gonorrhea):
- Ceftriaxone 250-500 mg IM as a single dose 1
Doxycycline component (for chlamydia and Mycoplasma genitalium):
- Doxycycline 100 mg orally twice daily for 7 days 4, 1, 5
- This regimen is highly effective for chlamydial urethritis and also covers M. genitalium 4
Alternative Regimen (If Doxycycline Contraindicated)
- Azithromycin 1 g orally as a single dose can replace doxycycline 4, 1
- Single-dose regimens have the advantage of improved compliance and directly observed treatment 4
Additional Alternative Options
If neither doxycycline nor azithromycin can be used 4:
- Erythromycin base 500 mg orally four times daily for 7 days
- Erythromycin ethylsuccinate 800 mg orally four times daily for 7 days
- Levofloxacin 500 mg orally once daily for 7 days
- Ofloxacin 300 mg orally twice daily for 7 days
Critical Management Steps
Sexual abstinence requirements:
- Patients must abstain from sexual intercourse for 7 days after therapy initiation AND until symptoms resolve AND until all partners are adequately treated 4, 1
Partner management:
- All sexual partners within the preceding 60 days must be referred for evaluation and treatment 4, 1
- Partners should receive treatment effective against chlamydia regardless of whether a specific etiology is identified 1
Comprehensive STI screening:
- All patients with urethritis should be tested for both N. gonorrhoeae and C. trachomatis to guide subsequent management 4, 1, 2
- HIV and syphilis testing should be performed as part of the comprehensive STI panel 4, 1
When to Suspect Urethritis (Diagnostic Criteria)
At least one of the following must be present 4, 1, 2:
- Mucopurulent or purulent urethral discharge
- Gram stain of urethral secretions showing ≥5 WBC per oil immersion field (or ≥2 WBC per oil immersion field in some guidelines)
- Positive leukocyte esterase test on first-void urine
- Microscopic examination of first-void urine showing ≥10 WBC per high-power field
Common Pitfalls to Avoid
Do not treat for gonorrhea alone without chlamydia coverage, as co-infection is extremely common and single-agent therapy will fail to eradicate both pathogens 1, 2
Do not wait for culture results to initiate treatment in symptomatic patients, as this increases transmission risk and complications 1
Do not forget to dispense medications on-site when possible and directly observe the first dose to maximize compliance 4
Do not use fluoroquinolones as first-line empiric therapy due to increasing resistance patterns, particularly in urology departments or patients who have used fluoroquinolones in the last 6 months 4
Follow-Up Considerations
- Patients should return for evaluation if symptoms persist or recur after completion of therapy 4
- Failure to improve within 3 days requires diagnostic reevaluation 1
- Repeat testing is not recommended less than 3 weeks after treatment due to risk of false-positive results 2
- Patients treated for sexually transmitted infections should have repeat screening in 3 months 2
Special Populations
HIV-positive patients: