What is the empiric treatment for a sexually active adult male with symptoms of urethritis, such as dysuria and possibly pyuria, without visible discharge?

Empiric Treatment for Urethritis in Sexually Active Adult Males

First-Line Empiric Therapy

For a sexually active adult male with urethritis symptoms (dysuria, possible pyuria) without visible discharge, treat empirically with doxycycline 100 mg orally twice daily for 7 days while awaiting test results for gonorrhea and chlamydia. 1

• Doxycycline has replaced azithromycin as the preferred first-line therapy due to emerging antimicrobial resistance concerns, particularly with Mycoplasma genitalium 1
• If gonorrhea cannot be ruled out clinically or epidemiologically, add ceftriaxone or cefixime to cover both pathogens 2

When to Treat Empirically vs. Defer Treatment

Treat Empirically If:

• The patient is at high risk for infection AND unlikely to return for follow-up (e.g., adolescents with multiple partners) 3
• In these cases, treat for both gonorrhea and chlamydia even without objective confirmation of urethritis 4, 3

Defer Treatment If:

• None of the following objective criteria are present: 5, 3
  • Mucopurulent or purulent urethral discharge
  • ≥5 WBCs per oil immersion field on Gram stain of urethral secretions
  • Positive leukocyte esterase test on first-void urine
  • ≥10 WBCs per high-power field on microscopic examination of first-void urine
• Instead, perform nucleic acid amplification testing for N. gonorrhoeae and C. trachomatis and treat based on results 3

Critical Diagnostic Considerations

The absence of pyuria does not exclude sexually transmitted urethritis, as urethral swabs and first-catch urine have low sensitivity (29-62%) for detecting polymorphonuclear leukocytes 1

• Nucleic acid amplification tests are more sensitive than traditional culture techniques and are the preferred diagnostic method 4
• Gram stain is the preferred rapid diagnostic test when available, as it can simultaneously document urethritis and identify gonococcal infection 4

Alternative First-Line Option

Azithromycin 1 g orally as a single dose remains an acceptable alternative, particularly when compliance is a concern 5, 6

• Advantages: Single-dose ensures compliance and allows directly observed therapy 5
• Disadvantages: Increasing resistance in M. genitalium (60-70% treatment failure rates) makes this less preferred 1, 7
• Azithromycin is FDA-approved for urethritis due to C. trachomatis or N. gonorrhoeae 6

Likely Pathogens

• Chlamydia trachomatis: 15-55% of NGU cases 4
• Mycoplasma genitalium: Up to one-third of NGU cases 1, 8
• Ureaplasma urealyticum: 10-30% of cases 8
• Trichomonas vaginalis and HSV: Less common but should be considered in refractory cases 4

Essential Partner Management

All sexual partners within the preceding 60 days must be evaluated and treated with the same empiric regimen, even if asymptomatic 5, 1

• Both patient and partners should abstain from sexual intercourse until 7 days after therapy is initiated and symptoms have resolved 5
• Expedited partner treatment (giving prescriptions to partners without examination) is advocated by the CDC and approved in many states 2

Management of Persistent or Recurrent Symptoms

If symptoms persist after completing initial doxycycline:

• Re-confirm objective signs of urethritis with microscopy 8
• Rule out non-compliance or partner reinfection 5, 8
• Test for Trichomonas vaginalis 5
• Consider M. genitalium testing if available, as this pathogen shows extremely high treatment failure rates (60-70%) with standard regimens 1, 9

Recommended treatment for persistent/recurrent urethritis:

• Metronidazole 2 g orally as a single dose PLUS azithromycin 1 g orally as a single dose (if not used initially) 5
• Alternative: Moxifloxacin 400 mg orally once daily for 7-14 days if M. genitalium is confirmed 1, 8

Common Pitfalls to Avoid

• Do not treat based on symptoms alone without objective evidence of urethritis unless the patient meets high-risk criteria for empiric treatment 3
• Do not rely on semen analysis to diagnose urethritis—it is used for fertility or prostatitis evaluation, not urethritis 5
• Do not use azithromycin as first-line without test of cure for M. genitalium, as this will select and increase macrolide-resistant strains in the population 8, 7
• Always perform serologic testing for syphilis in all patients with sexually-transmitted urethritis, as antimicrobial agents used for NGU may mask or delay symptoms of incubating syphilis 6

Follow-Up Recommendations

• Patients should return if symptoms persist or recur after treatment 5, 3
• Test-of-cure is not recommended for asymptomatic patients who received recommended treatment 5
• Consider repeat testing 3-6 months after treatment due to high reinfection rates 5, 3
• If positive for M. genitalium, test of cure samples should be collected no earlier than three weeks after start of treatment 8