Should we treat a confirmed or suspected Ureaplasma infection in various patient populations, including pregnant women and immunocompromised individuals?

Treatment of Ureaplasma Infection

Ureaplasma should be treated in specific clinical contexts—primarily symptomatic nongonococcal urethritis, pregnant women with symptoms of preterm labor, and immunocompromised patients with invasive disease—but routine screening and treatment of asymptomatic colonization is not recommended.

When to Treat Ureaplasma

Symptomatic Urethritis in Men

• Treat all cases of confirmed nongonococcal urethritis (NGU) with doxycycline 100 mg orally twice daily for 7 days, as Ureaplasma urealyticum causes 20-40% of NGU cases 1
• If symptoms persist after initial doxycycline treatment and reinfection/noncompliance are excluded, retreat with erythromycin base 500 mg orally 4 times daily for 14 days to cover possible tetracycline-resistant U. urealyticum 1
• Document urethritis before treating by demonstrating ≥5 WBCs per oil immersion field on urethral Gram stain, mucopurulent discharge, or positive leukocyte esterase test 1

Chronic Urinary Symptoms in Women

• Consider Ureaplasma as a cause in women with chronic dysuria, frequency, and urgency when standard urine cultures are negative 2
• Culture specifically for U. urealyticum and M. hominis before pursuing invasive testing for interstitial cystitis 2
• Treat positive cultures with azithromycin 1 g single dose; if infection persists, use doxycycline, ofloxacin, or erythromycin for 7 days 2
• In one study, 48% of women with chronic voiding symptoms had positive Ureaplasma cultures, and treatment resulted in significant symptom improvement (mean severity score 2.2 to 0.7, P <0.001) 2

Pregnant Women

• Screen and treat symptomatic pregnant women at 25-37 weeks gestation who present with signs of potential preterm labor 3
• Treatment with clindamycin in colonized symptomatic pregnant women reduced preterm birth rates (40.9% in treated Ureaplasma-positive vs 44.1% in uncolonized, p=0.024) and neonatal respiratory complications (10.9% vs 12.8%, p=0.050) 3
• Azithromycin 1-2 g orally is an acceptable alternative for pregnant women with combined gonorrhea and chlamydial infection, and azithromycin has activity against Ureaplasma 4, 5
• Do not routinely screen or treat asymptomatic bacteriuria in pregnant women without other risk factors, though this recommendation primarily addresses typical uropathogens rather than Ureaplasma specifically 1

Immunocompromised Patients

• Treat invasive Ureaplasma infections in immunosuppressed patients (including those on rituximab, with HIV, or other immunodeficiency) with doxycycline 6
• Maintain high clinical suspicion as Ureaplasma lacks a cell wall, making standard cultures difficult and often negative 6
• Consider 16S rRNA PCR assays when invasive infection is suspected but cultures remain negative 6
• Immunosuppressed patients have higher colonization rates and increased risk of disseminated disease including intra-abdominal abscesses and empyema 6

When NOT to Treat Ureaplasma

Asymptomatic Colonization

• Do not screen or treat asymptomatic bacteriuria in women without risk factors, postmenopausal women, elderly institutionalized patients, or patients with recurrent UTIs 1
• Asymptomatic bacteriuria may protect against superinfecting symptomatic UTI, and treatment risks selecting antimicrobial resistance 1

Before Urologic Procedures

• Screen for and treat asymptomatic bacteriuria (including Ureaplasma if specifically identified) only before urological procedures breaching the mucosa 1
• Antifungal prophylaxis for asymptomatic funguria does not require concurrent Ureaplasma treatment unless specific risk factors are present 1

Antimicrobial Susceptibility and Drug Selection

First-Line Therapy

• Doxycycline remains the drug of choice with 91% susceptibility among Ureaplasma isolates 7
• Josamycin shows 86% susceptibility, followed by ofloxacin (77%) and azithromycin (71%) 7

Serovar Considerations

• Serovar 3/14 is the most frequently isolated strain, followed by serovars 1 and 6, suggesting possible pathogenic predominance 7
• The majority of treatment failures occur with tetracycline-resistant strains, necessitating extended erythromycin regimens 1

FDA-Approved Activity

• Azithromycin demonstrates in vitro activity against Ureaplasma urealyticum, though clinical significance for this specific indication has not been established in adequate controlled trials 4
• At least 90% of Ureaplasma urealyticum isolates exhibit MIC ≤4 mcg/mL for azithromycin 4

Critical Pitfalls to Avoid

• Never treat persistent urethritis empirically without excluding reinfection or noncompliance first—these are more common than treatment failure 1
• Do not rely on standard urine cultures alone when Ureaplasma is suspected; specific mycoplasma culture or molecular testing is required 2, 6
• Avoid fluoroquinolones in pregnant women despite their activity against Ureaplasma, as they are contraindicated during pregnancy 1, 5
• Do not interpret positive Ureaplasma cultures as automatically pathogenic in asymptomatic patients—colonization is common and treatment may eliminate protective flora 1
• Ensure partner notification and treatment for all diagnosed cases of NGU to prevent reinfection 1