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

From the Guidelines

The treatment for Mycoplasma genitalium (M. genitalium) infection is Azithromycin 500 mg p.o. on day 1, with an alternative regimen of Moxifloxacin 400 mg q.d. for 7-14 days in cases of macrolide resistance. According to the European Association of Urology guidelines on urological infections, summarized in the 2024 guidelines 1, the recommended treatment for M. genitalium infection is Azithromycin. Some key points to consider when treating M. genitalium infection include:

• The use of Azithromycin as the first-line treatment, due to its efficacy and safety profile 1
• The consideration of Moxifloxacin as an alternative regimen in cases of macrolide resistance, as outlined in the guidelines 1
• The importance of treating sexual partners simultaneously to prevent reinfection
• The need for follow-up testing 3-4 weeks after completing treatment to confirm cure, especially given rising antibiotic resistance
• The recommendation to screen patients for other sexually transmitted infections, as co-infections are common. It is essential to note that M. genitalium is a slow-growing bacterium that lacks a cell wall, making it resistant to many common antibiotics like penicillins and cephalosporins, which is why Azithromycin and Moxifloxacin are the preferred treatment options 1.

From the Research

Treatment Options for Mycoplasma genitalium Infection

• The current guidelines recommend 1 g of azithromycin as the first-line treatment for M. genitalium infection 2, 3, 4.
• Azithromycin has a cure rate of 85-95% in macrolide-susceptible infections 3, 4.
• An extended course of azithromycin appears to have a higher cure rate, and pre-treatment with doxycycline may decrease organism load and the risk of macrolide resistance selection 4.
• Moxifloxacin can be used as second-line therapy, but resistance is increasing 2, 3, 4, 5.
• Uncomplicated M. genitalium infection without macrolide resistance mutations or resistance testing can be treated with azithromycin 500 mg on day one, then 250 mg on days 2-5 (oral) 4.
• Second-line treatment and treatment for uncomplicated macrolide-resistant M. genitalium infection is moxifloxacin 400 mg od for 7 days (oral) 4.
• Third-line treatment for persistent M. genitalium infection after azithromycin and moxifloxacin can be doxycycline or minocycline 100 mg bid for 14 days (oral) or pristinamycin 1 g qid for 10 days (oral) 4, 5.
• Complicated M. genitalium infection (PID, epididymitis) can be treated with moxifloxacin 400 mg od for 14 days 3, 4.

Resistance and Treatment Failure

• Macrolide resistance is increasing, and azithromycin treatment failure has been reported 6, 5.
• The emergence of antimicrobial-resistant M. genitalium, driven by suboptimal macrolide dosage, threatens the continued provision of effective and convenient treatments 5.
• A strong and consistent association exists between the presence of 23S rRNA gene mutations and azithromycin treatment failure 5.
• Fluoroquinolones such as moxifloxacin remain highly active against most macrolide-resistant M. genitalium, but cases of moxifloxacin treatment failure have been reported 2, 5.