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Mycoplasma Genitalium

The sexually transmitted infection Mycoplasma genitalium (Mgen) is an emerging health concern and has recently been identified as highly prevalent.1 In certain populations, rates have shown to be higher than gonorrhea, and at times higher than chlamydia.6

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Potential Health Risks 

In men, infection with Mgen can cause symptomatic and asymptomatic urethritis. In women, Mgen infection can double the risk of cervicitis, pelvic inflammatory disease (PID), preterm delivery, infertility and more. It is also associated with an increased risk of acquiring HIV or nongonococcal urethritis.2-4 Unfortunately, many people with Mgen will not be aware they have it. Most cases are asymptomatic, and any associated symptoms are similar to those caused by other STIs like chlamydia.

Risk Factors

Those most at risk for Mgen infection include those who engage in unprotected vaginal or anal sex, engage in high-risk sexual behavior, have sexual contact with individuals diagnosed with an STI or PID, or have contact with individuals infected with Mgen.2,5

Mgen is an emerging health concern that:

  • Is an extremely slow-growing organism2
  • Causes symptomatic and asymptomatic urethritis among men2
  • Frequently causes asymptomatic infections among women2
  • Is often the sole pathogen; however, infection with C. trachomatis is common in selected geographic areas
  • Is more common among people ages 15 to 24 years than in people ages 35 to 39 years3
  • Can be difficult to treat due to rapidly rising incidence of macrolide resistance2

The presence of Mgen is associated with an increased risk of acquiring HIV2-4

Antibiotic Resistance In Mgen

Resistance to azithromycin has been rapidly increasing and has been confirmed in multiple studies. Prevalence of molecular markers for macrolide resistance, which highly correlates with treatment failure, ranges from 44% to 90% in the United States.6,7 This complicates the treatment of Mgen infection by empiric antibiotic regimens. 

Clinical treatment failure and high-level in vitro macrolide resistance have been linked with mutations in the 23S rRNA gene of M. genitalium.

Macrolide resistance mediating mutations have been observed in 20-80% of cases.7,8

Two-stage therapy approaches, ideally using resistance-guided therapy, are recommended for treatment. Resistance-guided therapy has demonstrated cure rates of >90% and should be used whenever possible; however, it requires access to macrolide-resistance testing.2

The importance of two


Mgen can be difficult to detect because the bacterial organism load is low compared to other STIs commonly tested for. This means that a highly sensitive rRNA test is needed for accurate diagnosis.9 

Mgen is a slow-growing organism, so nucleic acid amplification testing (NAAT) is the only viable diagnostic solution and is recommended by the CDC.2

Testing is recommended for women with recurrent cervicitis and should be considered in women with PID2

  • Prevalence of 18.3%14
  • Detected in 10%-30% of women with clinical cervicitis2,15
  • Identified in up to 22% of pelvic inflammatory disease (PID) cases2,15
  • Untreated PID can lead to adverse pregnancy outcomes2,15

Testing is recommended for men with recurrent non-gonococcal urethritis

  • Prevalence of 16.5%14
  • More likely to exhibit symptoms of Mgen infection15
  • Responsible for 40% of persistent or recurrent urethritis in men2

Guide to therapy 

Guidelines for Mgen infections now recommend testing for macrolide resistance to help determine appropriate treatment.11,12,13 

When applying resistance-guided therapy to a population with high levels of antibiotic resistance and cure rates below 67%, patient outcome was significantly improved.12 

Cure rates in the Mgen macrolide-susceptible population exceeded 94%. Using doxycycline for initial STI treatment reduces overall use of azithromycin and reduces initial bacterial load which may improve subsequent Mgen treatment.7

Resistance treatment failure

With increasing antibiotic resistance, there is a need to detect mutations conferring macrolide resistance when they are present.

Mgen treatment failures can occur when using doxycycline, azithromycin and moxifloxacin. Microbiologic cure rates are poor with either doxycycline or azithromycin monotherapy (~50% or less). Microbiologic cure rates for moxifloxacin were initially high (close to 100%) but have declined to 89% in studies conducted from 2010-2017.10

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  1. Centers for Disease Control and Prevention. Mycoplasma genitalium: CDC detailed fact sheet. Updated December 5, 2022. Accessed February 12, 2024.
  2. Workowski KA, Bachmann LH, Chan PA, et al. Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm Rep. 2021;70(4):1-187. Published 2021 Jul 23. doi:10.15585/mmwr.rr7004a1 
  3. Jensen JS, Bradshaw CS, Tabrizi SN, Fairley CK, Hamasuna R. Azithromycin treatment failure in Mycoplasma genitalium-positive patients with nongonococcal urethritis is associated with induced macrolide resistance. Clin Infect Dis. 2008;47(12):1546-1553. doi:10.1086/593188 
  4. Napierala Mavedzenge S, Weiss HA. Association of Mycoplasma genitalium and HIV infection: a systematic review and meta-analysis. AIDS. 2009;23(5):611-620. doi:10.1097/QAD.0b013e328323da3e 
  5. Mobley V and Sena AC. Mycoplasma genitalium infection in men and women. 2019.
  6. Getman D, Jiang A, O'Donnell M, Cohen S. Mycoplasma genitalium Prevalence, Coinfection, and Macrolide Antibiotic Resistance Frequency in a Multicenter Clinical Study Cohort in the United States. J Clin Microbiol. 2016;54(9):2278-2283. doi:10.1128/JCM.01053-16 
  7. Read TRH, Fairley CK, Murray GL, et al. Outcomes of Resistance-guided Sequential Treatment of Mycoplasma genitalium Infections: A Prospective Evaluation. Clin Infect Dis. 2019;68(4):554-560. doi:10.1093/cid/ciy477 
  8. Jensen JS, Bradshaw C. Management of Mycoplasma genitalium infections - can we hit a moving target?. BMC Infect Dis. 2015;15:343. Published 2015 Aug 19. doi:10.1186/s12879-015-1041-6 
  9. Frølund M, Lidbrink P, Wikström A, Cowan S, Ahrens P, Jensen JS. Urethritis-associated Pathogens in Urine from Men with Non-gonococcal Urethritis: A Case-control Study. Acta Derm Venereol. 2016;96(5):689-694. doi:10.2340/00015555-2314 
  10. Centers for Disease Control and Prevention. Mycoplasma genitalium: CDC detailed fact sheet. Updated December 5, 2022. Accessed January 30, 2024. 
  11. Australian STI Management Guidelines. Mycoplasma genitalium. Accessed January 30, 2024. 
  12. Jensen JS, Cusini M, Gomberg M, Moi H. 2016 European guideline on Mycoplasma genitalium infections. J Eur Acad Dermatol Venereol. 2016;30(10):1650-1656. doi:10.1111/jdv.13849 
  13. Soni S, Horner P, Rayment M, et al. British Association for Sexual Health and HIV national guideline for the management of infection with Mycoplasma genitalium (2018). Int J STD AIDS. 2019;30(10):938-950. doi:10.1177/0956462419825948 
  14. Manhart. L, et al. Mycoplasma genitalium in the US (MyGeniUS): Surveillance data from 2020-2021. Oral presentation at CDC STD Prevention Conference; Sept 19-22. 
  15. Jensen et al., Mycoplasma genitalium: prevalence, clinical significance, and transmission, Sex Transm Infect. 2005;81:458–462.