In a healthy adult male presenting with urethral discharge, dysuria, or pelvic pain, how should Ureaplasma infection be diagnosed and treated?

Ureaplasma in Adult Males: Diagnosis and Treatment

Critical First Principle: Do Not Treat Asymptomatic Detection

Ureaplasma species detected in urine or urethral specimens of asymptomatic males should NOT be treated, as this represents normal colonization rather than infection. 1 Up to 80% of sexually active adults are colonized with Ureaplasma species without disease, and treating colonization promotes antimicrobial resistance without clinical benefit. 1

When to Diagnose and Treat

Diagnostic Criteria for True Urethritis

Treatment is indicated ONLY when BOTH clinical symptoms AND objective laboratory evidence are present: 2, 1

Clinical symptoms:

• Mucopurulent or purulent urethral discharge 2
• Dysuria or urethral pruritis 2
• Pelvic pain 1

Objective laboratory confirmation (at least ONE required):

• Gram stain showing ≥5 white blood cells per oil immersion field in urethral secretions 2, 1
• Positive leukocyte esterase on first-void urine 2
• Microscopic examination of first-void urine showing ≥10 white blood cells per high-power field 2

Important Diagnostic Nuance

• Ureaplasma urealyticum is the pathogenic species causing true urethritis 1
• Ureaplasma parvum has questionable pathogenic role and should generally not be treated 1, 3
• Specific diagnostic tests for Ureaplasma are NOT routinely indicated because detection does not alter standard nongonococcal urethritis (NGU) therapy 2
• Always test for N. gonorrhoeae and C. trachomatis first, as these are the principal proven pathogens 2

Treatment Algorithm

First-Line Therapy

Doxycycline 100 mg orally twice daily for 7 days is the preferred treatment, with 91% susceptibility rates. 2, 1, 3

Alternative Regimens (When Doxycycline Contraindicated)

• Azithromycin 1.0-1.5 g orally as single dose (71% susceptibility) 2, 1, 3
• Levofloxacin 500 mg orally once daily for 7 days 2
• Ofloxacin 200 mg orally twice daily for 7 days 2

Treatment Duration Modifications

• Standard urethritis: 7 days 2, 1, 3
• When prostatitis cannot be excluded: Extend to 14 days 1

Management of Persistent NGU After Initial Treatment

If symptoms persist after first-line doxycycline: 2

• Azithromycin 500 mg orally on day 1, then 250 mg daily for 4 days 2, 3

If symptoms persist after first-line azithromycin: 2

• Moxifloxacin 400 mg orally once daily for 7-14 days 2, 3
• Metronidazole 400 mg orally twice daily for 5 days (to cover Trichomonas vaginalis) 2

Partner Management (Critical for Treatment Success)

All sexual partners MUST be evaluated and treated to prevent reinfection—this is the most common cause of treatment failure. 1, 3

• Symptomatic patients: Treat partners with last sexual contact within 30 days of symptom onset 1, 3
• Asymptomatic patients (if treated): Treat partners with last sexual contact within 60 days of diagnosis 1, 3
• Partners should receive the same antibiotic regimen 3

Follow-Up Strategy

• Test-of-cure is NOT routinely recommended after doxycycline or azithromycin unless symptoms persist 1, 3
• Patients should return for evaluation only if symptoms persist or recur 3
• Do NOT retreat based on persistent symptoms alone without re-documenting objective signs of urethritis 3

Common Pitfalls to Avoid

1. Treating asymptomatic Ureaplasma detection—this is colonization, not infection, and promotes resistance 1, 3

2. Treating U. parvum specifically—its pathogenic role is questionable and it should not be targeted 1

3. Failing to treat sexual partners—this is the primary cause of treatment failure and recurrence 1

4. Using fluoroquinolones in high-risk populations (recent fluoroquinolone users, urology department patients) due to resistance concerns 1

5. Empiric treatment without documenting urethritis—only justified in high-risk patients unlikely to return for follow-up 2

6. Ordering specific Ureaplasma tests—these are not indicated as they do not change management of NGU 2

Context: Ureaplasma's Role in NGU

While Ureaplasma urealyticum and Mycoplasma genitalium have been implicated in NGU, C. trachomatis remains the most frequent identified cause (15-55% of cases). 2 The etiology of most nonchlamydial NGU cases remains unknown. 2 The proportion of NGU caused by chlamydia has been declining, but this does not change the empiric treatment approach. 2