How should Mycoplasma hominis and Ureaplasma infections be treated in a symptomatic adult non‑pregnant patient?

Treatment of Mycoplasma hominis and Ureaplasma in Symptomatic Adults

Doxycycline 100 mg orally twice daily for 7-14 days is the first-line treatment for symptomatic Mycoplasma hominis and Ureaplasma urealyticum infections in non-pregnant adults. 1, 2, 3, 4

Critical First Step: Confirm Treatment Is Actually Indicated

Before treating, you must verify this is truly a symptomatic infection requiring antibiotics:

• Do NOT treat asymptomatic colonization - 40-80% of sexually active adults carry these organisms without disease 2, 5
• Only treat documented symptomatic cases: nongonococcal urethritis in men (with >10 WBC/hpf on urethral smear), cervicitis/PID in women, or specific fertility contexts 1, 2, 5
• Rule out traditional STIs first - exclude Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, and Trichomonas vaginalis before attributing symptoms to Ureaplasma 5
• The European STI Guidelines Editorial Board explicitly states routine testing and treatment causes more harm than good through unnecessary antibiotic exposure and resistance development 5

Primary Treatment Regimen

Doxycycline remains the most effective tetracycline:

• Dosing: 100 mg orally twice daily for 7-14 days 1, 3, 4
• Doxycycline shows 83-95% susceptibility for both M. hominis and Ureaplasma species, making it superior to other tetracyclines 3, 4
• This regimen addresses the 20-40% of NGU cases caused by U. urealyticum and provides coverage for potential M. hominis co-infection 1, 2

Alternative Regimens (When Doxycycline Fails or Is Contraindicated)

If the patient fails initial doxycycline therapy or cannot tolerate it:

Fluoroquinolones (second-line):

• Ofloxacin shows >95% susceptibility against both species and is the preferred fluoroquinolone 3
• Levofloxacin 750 mg orally daily for 7-14 days is an acceptable alternative 6
• Avoid ciprofloxacin - only 35-70% susceptibility, with significant cross-resistance to erythromycin 3

Macrolides (limited utility):

• Josamycin or clarithromycin may work for Ureaplasma (MIC₉₀ 0.5 mg/L) but have poor activity against M. hominis 3
• Avoid erythromycin - high resistance rates (83.8% for U. urealyticum, nearly universal for M. hominis) 3, 4
• The 1993 CDC guidelines recommended erythromycin 500 mg four times daily for 7-14 days, but this is now obsolete given current resistance patterns 1, 3, 4

Clindamycin:

• Most potent against M. hominis specifically, but ineffective against Ureaplasma 3
• Reserve for documented M. hominis-only infections

Critical Resistance Patterns to Know

The antibiotic landscape has changed dramatically:

• Tetracycline resistance: 10-13% in M. hominis, 1-3% in Ureaplasma, but doxycycline maintains better activity 3, 7
• Macrolide resistance: 83-95% of U. urealyticum strains now resist clarithromycin, tetracycline, and erythromycin 4
• Cross-resistance exists: between tetracyclines (53-93%), between macrolides and erythromycin (70-100%), and between erythromycin and ciprofloxacin (43-55%) 3
• Resistance is mediated by tetM determinants, and in vitro resistance correlates with clinical treatment failure 8

Management of Treatment Failure

If symptoms persist after completing doxycycline:

1. Verify compliance and confirm partner was treated simultaneously 1
2. Re-evaluate for re-exposure to untreated sexual partners 1
3. Consider alternative diagnosis - perform wet mount and culture for T. vaginalis 1
4. Switch to extended alternative regimen: erythromycin base 500 mg four times daily for 14 days (though resistance makes this less reliable) or ofloxacin 1, 3
5. For persistent symptoms without objective signs of inflammation, reassure the patient that chronic symptoms don't cause complications and aren't necessarily sexually transmitted 1

Partner Management

All sexual partners require evaluation and treatment:

• Treat partners with last contact within 30 days of symptom onset (symptomatic patients) or 60 days of diagnosis (asymptomatic patients) 1
• If last intercourse preceded these intervals, treat the most recent partner 1
• Both patient and partners must abstain from intercourse until therapy is completed and both are asymptomatic 1

Common Pitfalls to Avoid

• Don't treat asymptomatic "positive tests" - this violates antimicrobial stewardship and drives resistance 2, 5
• Don't use commercial multiplex PCR panels indiscriminately - they detect colonization, not disease 5
• Don't assume all tetracyclines are equivalent - doxycycline has superior activity over tetracycline 3, 4
• Don't rely on erythromycin or clarithromycin given current resistance rates exceeding 80% 3, 4
• Don't forget to test for and treat traditional STIs first - these are more common and more consequential 5