What empiric antibiotic regimen should be used to treat a presumed genital infection with Mycoplasma hominis and Ureaplasma in an adult without contraindications?

Treatment of Mycoplasma hominis and Ureaplasma Infections

Treat empirically with doxycycline 100 mg orally twice daily for 7 days as first-line therapy for presumed genital Mycoplasma hominis and Ureaplasma infection. 1, 2, 3

First-Line Therapy

• Doxycycline 100 mg orally twice daily for 7 days remains the gold standard treatment, demonstrating excellent activity against both Ureaplasma species and Mycoplasma hominis with sustained susceptibility patterns. 1, 3, 4

• This regimen achieves microbiologic cure in the majority of cases and prevents organism-specific sequelae when the pathogen is susceptible. 5

• All Ureaplasma strains in recent surveillance showed 100% susceptibility to doxycycline, and it remains among the most potent agents against M. hominis alongside minocycline and ofloxacin. 4

Alternative First-Line Option for Compliance Concerns

• Azithromycin 1 g orally as a single dose provides equivalent efficacy to doxycycline (relative risk 1.03,95% CI 0.94-1.12) for Ureaplasma infections, with the critical advantage of directly observed treatment eliminating adherence problems. 1

• However, azithromycin data are stronger for Ureaplasma than for M. hominis, making doxycycline preferable when both organisms are suspected. 1, 3

Alternative Regimens for Doxycycline Intolerance

• Erythromycin base 500 mg orally four times daily for 7 days or erythromycin ethylsuccinate 800 mg orally four times daily for 7 days are CDC-recommended alternatives when tetracyclines cannot be used. 5, 1, 2

• For patients unable to tolerate high-dose erythromycin, extended lower-dose regimens are available: erythromycin base 250 mg orally four times daily for 14 days or erythromycin ethylsuccinate 400 mg orally four times daily for 14 days, though these have somewhat reduced efficacy. 5, 1

Fluoroquinolone Alternatives (Use With Caution)

• Levofloxacin 500 mg orally once daily for 7 days or ofloxacin 300 mg orally twice daily for 7 days may be considered, but persistent organism detection occurs in 30-36% of cases after fluoroquinolone therapy—substantially higher than with tetracyclines or macrolides. 1, 3

• Fluoroquinolones should be reserved for situations where tetracyclines and macrolides are contraindicated due to inferior microbiological eradication rates. 1

Management of Treatment Failure

• Before escalating therapy, verify patient compliance with the initial regimen and confirm re-exposure to untreated sexual partners has not occurred. 1, 3

• Require objective documentation of urethral inflammation (≥5 polymorphonuclear leukocytes per high-powered field on urethral smear) before initiating additional antimicrobial therapy—symptoms alone without laboratory evidence are insufficient for retreatment. 5, 1, 3

• After doxycycline failure with documented inflammation, switch to azithromycin 500 mg orally on day 1, followed by 250 mg daily for 4 days. 1, 3

• After azithromycin failure, escalate to moxifloxacin 400 mg orally once daily for 7-14 days. 1, 3

• For persistent infections after both doxycycline and erythromycin, extending erythromycin to 14 days (erythromycin base 500 mg orally four times daily for 14 days) targets possible tetracycline-resistant Ureaplasma strains. 5, 2

Partner Management

• Treat all sexual partners with last sexual contact within 60 days using identical first-line regimens (doxycycline or azithromycin). 1, 2, 3

• Patients and partners must abstain from sexual intercourse for 7 days after initiating single-dose therapy or until completion of 7-day regimens, provided symptoms have resolved. 1, 2, 3

Follow-Up Strategy

• Patients return for evaluation only if symptoms persist or recur after completing therapy—routine test-of-cure is not indicated for asymptomatic patients. 1, 3

• Persistent detection of organisms without inflammation does not warrant retreatment, as these infections are not known to cause complications or be sexually transmitted in the absence of symptoms. 5, 1

Special Populations

• HIV-infected patients receive identical treatment regimens as HIV-negative patients with no dose adjustments necessary. 1, 2, 3

Critical Pitfall to Avoid

• Do not treat based on symptoms alone without objective signs of urethritis in cases of persistent or recurrent symptoms—urologic examinations rarely reveal specific etiologies, and unnecessary antimicrobial exposure drives resistance. 5, 1

• The 7-day doxycycline duration is essential; shorter courses are insufficient to eradicate Ureaplasma urealyticum. 2