What is the recommended treatment for a patient with symptomatic Ureaplasma (Ureaplasma) infection, where other bacteria, Sexually Transmitted Infections (STIs), or Bacterial Vaginosis (BV) have been ruled out?

Treatment of Symptomatic Ureaplasma Infection

For symptomatic Ureaplasma infection with other STIs and BV excluded, treat with doxycycline 100 mg orally twice daily for 7 days as first-line therapy. 1, 2

First-Line Treatment Regimen

• Doxycycline 100 mg orally twice daily for 7 days is the CDC-recommended first-line treatment for Ureaplasma urealyticum infection 1, 2
• This regimen is specifically indicated for nongonococcal urethritis (NGU) caused by U. urealyticum 2
• Administer with adequate fluids to reduce risk of esophageal irritation; may be given with food or milk if gastric irritation occurs 2

Alternative First-Line Option

• Azithromycin 1 g orally as a single dose is an effective alternative, particularly when compliance with a 7-day regimen is uncertain 1, 3
• Single-dose azithromycin showed similar effectiveness to 7-day doxycycline in clinical trials 3
• This option offers the advantage of directly observed therapy and improved compliance 4

Additional Alternative Regimens

If doxycycline and azithromycin cannot be used:

• Erythromycin base 500 mg orally four times daily for 7 days 1
• Erythromycin ethylsuccinate 800 mg orally four times daily for 7 days 1
• Levofloxacin 500 mg orally once daily for 7 days 4, 1
• Ofloxacin 300 mg orally twice daily for 7 days 4, 1

Partner Management (Critical to Prevent Reinfection)

• All sexual partners within the preceding 60 days must be evaluated and treated with the same regimen 1, 5
• Partners with last sexual contact within 30 days of symptom onset (symptomatic patients) or within 60 days of diagnosis (asymptomatic patients) require treatment 1
• Both patient and partners must abstain from sexual intercourse for 7 days after initiating therapy (or until completion of 7-day regimen) and until symptoms resolve 1
• Failure to treat partners is a common pitfall leading to reinfection 5

Management of Persistent or Recurrent Symptoms

If symptoms persist after initial treatment:

Step 1: Confirm Objective Evidence

• Do not retreat based on symptoms alone—must document objective signs of urethritis (discharge or ≥5 WBCs per high-power field) 5
• Rule out non-compliance with initial regimen or re-exposure to untreated partner 5

Step 2: If Compliance and Partner Treatment Confirmed

• Some cases may be caused by tetracycline-resistant U. urealyticum 4, 5
• Test for Trichomonas vaginalis (culture or NAAT) 5

Step 3: Treatment for Persistent/Recurrent Cases

• Metronidazole 2 g orally as a single dose PLUS Azithromycin 1 g orally as a single dose (if not used initially) 5
• Alternative: Metronidazole 2 g orally as a single dose PLUS Erythromycin base 500 mg orally four times daily for 7 days 4, 5

Follow-Up Recommendations

• Patients should return for evaluation only if symptoms persist or recur after completing therapy 1
• If symptoms persist beyond 3 months, consider chronic prostatitis/chronic pelvic pain syndrome 5
• Re-treatment with initial regimen is appropriate if non-compliance or re-exposure to untreated partner is identified 1

Special Populations

• HIV-infected patients should receive the same treatment regimens as HIV-negative patients 1, 5
• Treatment is particularly important in HIV-infected individuals as urethritis may facilitate HIV transmission 4

Key Clinical Pitfalls to Avoid

• Never treat based on symptoms alone without objective evidence of urethritis 5
• Always address partner treatment—failure to do so is the most common cause of treatment failure 5
• Do not use fluoroquinolones (levofloxacin, ofloxacin) as first-line unless doxycycline and azithromycin are contraindicated, as resistance patterns vary geographically 4
• Ensure 7-day sexual abstinence after treatment initiation to prevent reinfection 1