What is the treatment for mycoplasma genitalium?

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Treatment for Mycoplasma Genitalium

For uncomplicated Mycoplasma genitalium infections, the first-line treatment is azithromycin 500 mg on day one, followed by 250 mg on days 2-5. 1

Treatment Algorithm

First-line Treatment

  • For macrolide-susceptible M. genitalium infections:
    • Azithromycin 500 mg on day one, then 250 mg on days 2-5 (extended regimen) 1, 2
    • Alternative: Azithromycin 1 g orally in a single dose 3

Second-line Treatment (for macrolide-resistant infections)

  • Moxifloxacin 400 mg once daily for 7 days 1, 2
    • Note: Moxifloxacin should be reserved for confirmed M. genitalium infections that have failed first-line therapy due to increasing resistance rates 1

Third-line Treatment (for persistent infections after azithromycin and moxifloxacin)

  • Doxycycline 100 mg twice daily for 14 days (cure rate 40-70%) 2
  • Pristinamycin 1 g four times daily for 10 days (cure rate ~75%) 2

Diagnostic Considerations

  • Testing for M. genitalium requires nucleic acid amplification testing (NAAT) 2
  • When available, testing should include investigation for macrolide resistance mutations to guide therapy 1, 2
  • Testing is primarily recommended for symptomatic individuals 1

Treatment Efficacy

  • Extended azithromycin regimen has shown higher cure rates (95-99%) compared to single-dose azithromycin for macrolide-susceptible infections 2, 4
  • Doxycycline alone has a low cure rate of only 30-40% for M. genitalium 2, 4
  • Moxifloxacin has a cure rate of approximately 92% for macrolide-resistant infections, but efficacy is significantly reduced (37.5%) in the presence of parC S83I mutations 5, 6

Antimicrobial Resistance Considerations

  • Macrolide resistance in M. genitalium is increasing globally, with rates exceeding 50% in many regions 6
  • Quinolone resistance is also increasing, particularly mutations in the parC gene (S83I) 5, 2
  • Single-dose azithromycin (1g) has been associated with selection of macrolide-resistant strains and should be avoided when possible 4

Follow-up Recommendations

  • Test of cure is recommended 14-28 days after completing treatment 5, 6
  • Patients should abstain from sexual intercourse until completion of treatment and resolution of symptoms 3
  • Sexual partners should be evaluated and treated to prevent reinfection 3

Special Considerations

  • For complicated M. genitalium infections (PID, epididymitis):
    • Moxifloxacin 400 mg once daily for 14 days 2
  • Resistance-guided therapy based on macrolide resistance testing is strongly recommended when available to optimize treatment outcomes 2

The treatment landscape for M. genitalium is challenging due to increasing antimicrobial resistance. Extended azithromycin regimens are preferred over single-dose therapy to reduce the risk of developing resistance, and treatment should be guided by resistance testing whenever possible.

References

Guideline

Management of Mycoplasma genitalium Infections

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

2021 European guideline on the management of Mycoplasma genitalium infections.

Journal of the European Academy of Dermatology and Venereology : JEADV, 2022

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Combination Therapy for Mycoplasma genitalium, and New Insights Into the Utility of parC Mutant Detection to Improve Cure.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2022

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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