What is the first-line treatment for Mycoplasma genitalium (M. genitalium) infection?

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Last updated: February 26, 2025View editorial policy

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From the Guidelines

The first-line treatment for Mycoplasma genitalium infection is Azithromycin 500 mg p.o. on day 1. According to the European Association of Urology guidelines on urological infections, published in 2024 1, Azithromycin is the recommended first-line treatment for M. genitalium infection. The guidelines suggest a dosage of 500 mg p.o. on day 1, with alternative regimens available in cases of macrolide resistance, such as Moxifloxacin 400 mg q.d. for 7-14 days.

Some key points to consider when treating M. genitalium infection include:

  • The importance of testing for cure 3-4 weeks after completing treatment, as M. genitalium has high rates of treatment failure 1
  • The need to treat sexual partners to prevent reinfection, and for patients to abstain from sexual activity until both they and their partners have completed treatment and symptoms have resolved
  • The challenges of treating M. genitalium due to its lack of a cell wall and development of resistance to multiple antibiotic classes through chromosomal mutations

In cases of macrolide resistance, Moxifloxacin 400 mg q.d. for 7-14 days is the recommended second-line therapy. It is essential to follow the guidelines and consider the specific circumstances of each patient when determining the best course of treatment for M. genitalium infection. The European Association of Urology guidelines provide a comprehensive overview of the recommended treatment regimens for various urological infections, including M. genitalium 1.

From the Research

First-Line Treatment for M. genitalium Infection

The first-line treatment for Mycoplasma genitalium (M. genitalium) infection is:

  • Azithromycin 500 mg on day one, then 250 mg on days 2-5 (oral) 2, 3 Some studies suggest that an extended course of azithromycin may have a higher cure rate 4, 5

Alternative Treatments

Alternative treatments for M. genitalium infection include:

  • Doxycycline, which has a cure rate of 30-40% but does not increase resistance 2, 3
  • Moxifloxacin, which can be used as second-line therapy but resistance is increasing 2, 3
  • Josamycin 500 mg three times daily for 10 days (oral) 3
  • Pristinamycin 1 g four times daily for 10 days (oral), which has a cure rate of approximately 90% 3

Treatment Efficacy

A systematic review and meta-analysis found that moxifloxacin improved the microbiologic cure rate compared with azithromycin (odds ratio [OR] 2.79,95% confidence interval [CI], 1.06-7.35) 6 However, clinical cure and safety did not show a significant difference between azithromycin and moxifloxacin treatments 6

Macrolide Resistance

Macrolide resistance is a concern in the treatment of M. genitalium infection, with an increasing prevalence of macrolide-resistant strains 2, 5, 3 The use of azithromycin 1 g single dose without test of cure may contribute to the development of macrolide resistance 5, 3

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

2021 European guideline on the management of Mycoplasma genitalium infections.

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

Research

2016 European guideline on Mycoplasma genitalium infections.

Journal of the European Academy of Dermatology and Venereology : JEADV, 2016

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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