What are the treatment options for Mycoplasma genitalium and Ureaplasma infections?

Treatment of Mycoplasma genitalium and Ureaplasma Infections

For Mycoplasma genitalium, use azithromycin 500 mg on day 1, then 250 mg daily on days 2-5 as first-line therapy, achieving 85-95% cure rates in macrolide-susceptible infections, while for Ureaplasma, either azithromycin 1g single dose or doxycycline 100 mg twice daily for 7 days are equally acceptable first-line options. 1, 2, 3

Mycoplasma genitalium Treatment Algorithm

First-Line Therapy

• Azithromycin extended regimen: 500 mg orally on day 1, followed by 250 mg daily on days 2-5 is the preferred initial treatment, with cure rates of 85-95% in macrolide-susceptible infections. 1, 2, 3
• This extended azithromycin course is superior to the single 1g dose, which has contributed to widespread macrolide resistance development. 3
• The 2021 European guideline emphasizes that macrolide resistance testing should be performed whenever possible before treatment, as resistance mutations are now present in 43% of infections. 3, 4

Second-Line Therapy (Macrolide-Resistant or Treatment Failure)

• Moxifloxacin 400 mg orally once daily for 7 days for uncomplicated infections is the recommended second-line treatment. 2, 3
• Moxifloxacin cure rates have declined from 100% pre-2010 to 89% post-2010 due to emerging fluoroquinolone resistance. 5
• For complicated infections (PID, epididymitis), extend moxifloxacin to 14 days. 2, 3

Third-Line Options (Multiple Treatment Failures)

• Doxycycline 100 mg twice daily for 14 days may cure 30-70% of persistent infections, though it should never be used as monotherapy initially. 2, 3
• Pristinamycin 1g four times daily for 10 days achieves approximately 75-90% cure rates in highly resistant cases. 2, 3
• Combination therapy with doxycycline and sitafloxacin has shown promise for highly resistant infections that failed moxifloxacin and pristinamycin. 6

Critical Pitfall

• Never use azithromycin 1g single dose for M. genitalium - this regimen has directly contributed to the macrolide resistance crisis and should be abandoned. 3

Ureaplasma Treatment

First-Line Options (Equally Acceptable)

• Azithromycin 1g orally as a single dose provides the advantage of directly observed therapy and improved compliance. 7, 1
• Doxycycline 100 mg orally twice daily for 7 days is equally effective as first-line therapy. 7, 1

Alternative Regimens

• Erythromycin base 500 mg orally four times daily for 7 days when tetracyclines are contraindicated. 7, 8
• Erythromycin ethylsuccinate 800 mg orally four times daily for 7 days as an alternative erythromycin formulation. 7, 8
• Levofloxacin 500 mg orally once daily for 7 days. 7, 1
• Ofloxacin 300 mg orally twice daily for 7 days. 7, 1

Tetracycline-Resistant Ureaplasma

• For recurrent urethritis after doxycycline that may be caused by tetracycline-resistant U. urealyticum, use metronidazole 2g orally single dose PLUS erythromycin base 500 mg four times daily for 7 days. 7

Universal Follow-Up Requirements

Sexual Abstinence

• Patients must abstain from sexual intercourse for 7 days after initiating single-dose therapy or until completion of multi-day regimens AND resolution of symptoms. 7, 1, 9

Partner Management

• All sexual partners within the preceding 60 days require evaluation and treatment to prevent reinfection, regardless of symptoms. 7, 1, 9

Test of Cure Considerations

• Patients should return for evaluation only if symptoms persist or recur after treatment completion. 7, 9
• Symptoms alone without objective signs of urethritis are insufficient basis for re-treatment. 7
• For M. genitalium specifically, test of cure is increasingly important given rising resistance rates. 3

Additional STI Screening

• All patients diagnosed with M. genitalium or Ureaplasma should receive testing for other STIs including syphilis and HIV. 7, 9

Key Resistance Considerations

• Macrolide resistance in M. genitalium has reached 43% in some populations, making resistance-guided therapy essential when testing is available. 3, 4
• Fluoroquinolone resistance-associated mutations are present in 15% of M. genitalium infections and correlate with moxifloxacin treatment failure. 4
• The widespread use of azithromycin 1g single dose without test of cure has been the primary driver of macrolide resistance development. 2, 3