Treatment of Ureaplasma urealyticum Infection

Treat symptomatic Ureaplasma urealyticum infections with doxycycline 100 mg orally twice daily for 7 days as first-line therapy. 1, 2, 3, 4

When to Treat vs. When NOT to Treat

Only treat patients with documented symptoms or objective signs of infection:

Symptomatic urethritis (mucopurulent discharge, dysuria, urethral pruritus) warrants immediate treatment 1
Asymptomatic detection does NOT warrant treatment in most clinical scenarios, including routine infertility screening 2
The 2024 European Association of Urology guidelines emphasize that U. urealyticum (not U. parvum) is associated with male infertility, but there is no evidence that treating asymptomatic infections improves conception rates 2

Critical distinction: U. urealyticum is pathogenic in nongonococcal urethritis, while U. parvum's role remains debated 1

Doxycycline 100 mg orally twice daily for 7 days 1, 2, 3, 4

This regimen provides optimal microbiologic cure and symptom resolution 1
Treatment duration should be 7 days for uncomplicated urethritis 1
FDA labeling confirms erythromycin 500 mg orally four times daily for at least 7 days when tetracyclines are contraindicated 5

When doxycycline is contraindicated or not tolerated:

For patients intolerant of high-dose erythromycin:

Fluoroquinolones (ofloxacin 300 mg twice daily or levofloxacin 500 mg once daily for 7 days) are additional alternatives 4

Algorithmic approach to persistent symptoms:

First, verify objective signs of urethritis (≥5 polymorphonuclear leukocytes per oil immersion field on urethral swab) before retreating 1
Assess compliance and partner treatment status:
- If non-compliant or partner untreated: re-treat with initial regimen 1, 4
If compliant with treated partner:
- Perform wet mount and culture for Trichomonas vaginalis 1
- If negative, switch to alternative regimen extended to 14 days (e.g., erythromycin base 500 mg four times daily for 14 days) 1
- This extended erythromycin regimen treats possible tetracycline-resistant U. urealyticum 1
Second-line after doxycycline failure: Azithromycin 500 mg on day 1, then 250 mg daily for 4 days 3, 4
Third-line after azithromycin failure: Moxifloxacin 400 mg once daily for 7-14 days 3, 4

All sexual partners require evaluation and treatment: 1, 3, 4

Treat partners with last sexual contact within 60 days of diagnosis 4
For symptomatic patients, treat partners with contact within 30 days of symptom onset 3
Both patient and partners must abstain from sexual intercourse for 7 days after single-dose therapy or until completion of 7-day regimen 4
Maintain patient confidentiality while ensuring partner notification 1

Test of cure is NOT routinely recommended: 3, 4

Patients should return for evaluation ONLY if symptoms persist or recur after therapy 1, 3, 4
Do not retreat based on persistent symptoms alone without documented objective signs of urethritis 1, 3
If test of cure is performed, wait at least 3 weeks after treatment completion 4
Consider test of cure after erythromycin treatment due to lower efficacy 4

Do not screen or treat asymptomatic patients routinely:

Asymptomatic infertile men should NOT be screened for Ureaplasma, as treatment does not improve conception rates 2
Asymptomatic bacteriuria does not warrant treatment in most cases 3

Do not confuse U. urealyticum with U. parvum:

Only U. urealyticum is definitively associated with NGU and male infertility 1, 2

Do not retreat without objective evidence:

Persistent symptoms without documented urethritis (≥5 PMNs per field) do not warrant additional antibiotics 1, 3
Patients with persistent symptoms after doxycycline and erythromycin failure should be reassured that the condition does not cause complications, even if symptoms persist 1

Ensure partner treatment to prevent ping-pong reinfection:

Treatment failure is often due to untreated partners rather than antibiotic resistance 1, 4