Treatment for Ureaplasma Infections

Doxycycline 100 mg orally twice daily for 7 days is the first-line treatment for Ureaplasma urealyticum infections. 1, 2, 3, 4, 5

First-Line Treatment

Doxycycline 100 mg orally twice daily for 7 days is the most consistently recommended and effective treatment across all major guidelines (European Association of Urology 2024, CDC, FDA-approved indication). 1, 2, 3, 4, 5
This regimen has demonstrated reliable efficacy in clinical trials and maintains the strongest evidence base for eradicating Ureaplasma urealyticum. 2, 3, 4
The FDA specifically approves doxycycline for nongonococcal urethritis caused by Ureaplasma urealyticum at this dosing. 5

Azithromycin 1.0-1.5 g orally as a single dose is an effective alternative when compliance with a 7-day regimen is a concern. 1, 2, 3, 4
Single-dose azithromycin showed similar effectiveness to 7-day doxycycline in head-to-head trials, though doxycycline remains preferred by most guidelines. 6
Azithromycin offers the advantage of directly observed single-dose therapy, eliminating compliance issues. 2, 4

Levofloxacin 500 mg orally once daily for 7 days is an alternative option. 1, 2, 3, 4
Ofloxacin 300 mg orally twice daily for 7 days is an alternative option. 1, 3, 4
Erythromycin base 500 mg orally four times daily for 7 days or erythromycin ethylsuccinate 800 mg orally four times daily for 7 days are alternatives, though less convenient due to dosing frequency. 1, 2, 3, 4
Avoid empiric fluoroquinolones in patients from urology departments or those who used fluoroquinolones in the last 6 months due to high resistance rates. 4

Only treat when symptoms of urethritis are present (urethral discharge, dysuria, urethral pruritus) or when documented urethritis exists (≥5 PMNs/HPF on urethral smear). 4
Perform nucleic acid amplification testing (NAAT) on first-void urine or urethral swab before treatment to confirm diagnosis. 3
Do not treat asymptomatic bacteriuria unless the patient is undergoing traumatic urinary tract procedures. 4
Recent data suggests U. urealyticum (but not U. parvum) is a true etiological agent in non-gonococcal urethritis, so species differentiation matters when available. 3, 4

Consider extending treatment to 14 days in men when prostatitis cannot be excluded. 4
For more severe or chronic urinary tract infections, 100 mg every 12 hours may be continued beyond the standard 7-day course. 5

Confirm objective signs of urethritis before initiating additional antimicrobial therapy—symptoms alone are insufficient. 1, 3, 4
If the patient was non-compliant or had re-exposure to an untreated partner, re-treat with the initial regimen. 1, 2
After first-line doxycycline failure: Use azithromycin 500 mg orally on day 1, followed by 250 mg daily for 4 days. 1, 2, 3
After first-line azithromycin failure: Use moxifloxacin 400 mg orally once daily for 7-14 days. 1, 2, 3, 4
Some cases of recurrent urethritis following doxycycline may be caused by tetracycline-resistant U. urealyticum, warranting alternative therapy. 1
For macrolide-resistant infections, moxifloxacin 400 mg once daily for 7-14 days is the preferred second-line treatment. 3
Pristinamycin 1 g four times daily for 10 days can be used as a third-line option after moxifloxacin failure, with approximately 75% cure rate. 3

All sexual partners within the preceding 60 days must be evaluated and treated while maintaining patient confidentiality. 1, 2, 3, 4
For symptomatic patients, treat partners with last sexual contact within 30 days of symptom onset; for asymptomatic patients, within 60 days of diagnosis. 4
Patients and partners must abstain from sexual intercourse until 7 days after therapy is initiated or until therapy is completed and symptoms have resolved. 1, 2, 3
Failure to address untreated partners is a common cause of apparent treatment failure. 4

Patients should return for evaluation only if symptoms persist or recur after completing therapy. 1, 2, 3
Objective signs of urethritis must be documented before re-treatment—do not re-treat based on symptoms alone. 1, 3
Urologic examination may be considered for persistent cases, though it often does not reveal a specific etiology. 1, 2

HIV-infected patients should receive the same treatment regimens as HIV-negative patients. 1, 2, 3
Gonococcal urethritis, chlamydial urethritis, and non-gonococcal urethritis may facilitate HIV transmission, making prompt treatment essential. 1

Administer with adequate fluid to reduce risk of esophageal irritation and ulceration. 5
If gastric irritation occurs, doxycycline may be given with food or milk without significantly affecting absorption. 5
Doxycycline does not require dose adjustment in renal impairment at usual recommended doses. 5