Understanding and Addressing Mycoplasma Genitalium to Protect Women’s Reproductive Health

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First identified more than 40 years ago (1981),1 Mycoplasma genitalium (M. genitalium) remains a lesser known sexually transmitted infection (STI), in part because FDA-cleared diagnostic tests have only been available since 2019.2 Data are limited regarding the long-term effects of M. genitalium infection on women’s reproductive health, but what we do know about this tiny pathogen is too compelling to overlook. In 2015 the U.S. Centers for Disease Control and Prevention (CDC) described M. genitalium as an “emerging issue,” but the CDC amended this description and gave M. genitalium its own independent section in the 2021 STI Treatment Guidelines.3

With these new guidelines and availability of clinically validated nucleic acid amplification tests (NAATs), OB/GYNs are now better positioned to identify the pathogen and improve treatment. M. genitalium is frequently not diagnosed and often overlooked as a possible infection because of lack of awareness and that the clinical presentation is similar to long-established STIs like Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Trichomonas vaginalis (TV).4-5 Symptoms like abnormal discharge, vaginal irritation, and pain during urination or sex may indicate M. genitalium as the sole infection or often as a coinfection with another STI. Moreover, the available data indicate that, among women with recurrent cervicitis or pelvic inflammatory disease (PID), prevalence of M. genitalium can be as high as 10-30%.3

Detection of M. genitalium Based on CDC Guidelines

M. genitalium has been found to be associated with a twofold increase in a woman’s risk of cervicitis, pelvic inflammatory disease (PID), preterm delivery, spontaneous abortion, and infertility.6 Available data reveal a significant correlation between the presence of M. genitalium and other STI pathologies, including, potentially, human immunodeficiency virus (HIV).1 Knowing whom to test and when is essential because the treatment protocol for M. genitalium is distinct from treatments for more commonly diagnosed STIs.

Clinical testing for M. genitalium was impractical for many years because the lack of a cell wall makes it invisible to Gram stain microscopy and because the microbe can take up to six months to culture.1 Further, M. genitalium contains a single copy of genomic DNA; even tests that target specific repetitive DNA sequences in the M. genitalium genome miss an average of 40% of infections.7 The availability of an FDA-cleared NAAT assay using transcription-mediated amplification (TMA) to target the more abundant ribosomal RNA of the organism allowed improved diagnostic accuracy of up to 99%,8 since M. genitalium contains thousands of copies of rRNA. This advance provided the CDC with a practical basis for developing testing guidelines and the technology is now widely available for use by providers for their patients.

The CDC guidelines recommend testing for M. genitalium by means of an FDA-cleared NAAT.3 Although the assay may be used with both swabs and urine specimens, vaginal swabs are preferred for detection of all STIs.9 In addition, providers performing routine screening for other STIs with a vaginal swab can simply add M. genitalium to the assays already being run on a single specimen. This can expedite treatment for patients who might otherwise be undiagnosed or assumed to have a different infection.

OB/GYNs see multiple patients a day and it’s important to consider what the CDC’s testing guidelines look like in clinical practice. Consistent with STI rates overall, M. genitalium most often infects women in the 15 to 25-year age range and is more prevalent among Black andHispanic women, who remain at higher risk for STIs in general.10 The 2021 CDC guidelines recommend testing for M. genitalium in women with recurring cervicitis and recommend that providers consider testing for the organism in women with PID.

Identifying M. genitalium in patients with recurrent cervicitis is key because the treatment protocol is different. Recurrent cervicitis is diagnosed in patients who present with continued inflammation of the cervical tissue, and where re-exposure to infection did not occur.

Likewise, although PID is historically associated with CT, NG, and TV, M. genitalium has been identified in up to 22% of women with PID,3 so providers should strongly consider including the M. genitalium assay in the testing order.Treatments for STIs can be simple when the right treatment is provided to the right patient, helping to avoid unnecessary complications.

Treatment for M. genitalium in a World of Resistance

Antimicrobial resistance is a growing challenge in the treatment of STIs overall, and M. genitalium is on the CDC’s antimicrobial resistance threat list.11 Additionally, not all providers have access to resistance testing. Thus, the CDC recommends two treatment options for M. genitalium, depending on the availability of resistance testing.

The primary coursefor M. genitalium infection is doxycycline 100 mg orally twice daily for 7 days, followed by moxifloxacin 400 mg orally twice daily for 7 days for a macrolide resistant infection, or where resistance testing is unavailable. If the provider has access to resistance testing, and the strain is macrolide sensitive, the moxifloxacin regimen may be substituted for a course of azithromycin 1 g orally initial dose, followed by 500 mg orally daily for 3 additional days (2.5g total).3

The CDC also advises that sex partners of anyone who tests positive for M. genitalium can be treated with the same microbial regimen, even if testing the partner is not possible.3 All antibiotic regimens are contraindicated during pregnancy, and pregnant patients diagnosed with M. genitalium infection should consult with a specialist to manage care.3

Compliance must also be top of mind for providers to help patients clear STIs, including M. genitalium infection. Likewise, it is important to impress upon patients who are asymptomatic that failure to complete an antibiotic course can result in a persistent infection, which can have lifelong adverse effects on their sexual and reproductive health.

OB/GYNs: Protectors of Reproductive Health

OB/GYNs contend with a wide range of clinical, psychological, and cultural challenges associated with sexual and reproductive health—and the landscape is not an even field for all patients. The unsatisfactory rate of STI infection in a developed nation like the U.S. is at least partly the result of unequal access to care and quality information. So, when a provider has a patient in the room and has reason to suspect M. genitalium infection, the opportunity and capability to add one test to a single specimen swab should be considered. More research and data are needed about M. genitalium in order to fully understand its clinical relevance in gynecological health, and the more providers diagnose M. genitalium, the more we will learn. With the availability of highly sensitive NAAT testing, healthcare providers are now more equipped than ever to make informed decisions about the right treatment course to safeguard their patients’ short- and long-term health.

References

  1. Taylor-Robinson D; Jensen JS. Mycoplasma genitalium: from chrysalis to multicolored butterfly. Clin Microbiol Rev. 2011;24(3):498-514.
  2. U.S. Food and Drug Administration. FDA permits marketing of first test to aid in the diagnosis of a sexually-transmitted infection known as Mycoplasma genitalium. 2019. https://www.fda.gov/news-events/press-announcements/fda-permits-marketing-first-test-aid-diagnosis-sexually-transmitted-infection-known-mycoplasma. Accessed February 23, 2024.
  3. Workowski KA, et al. Sexually Transmitted Infections Treatment Guidelines 2021. MMWR Recomm Rep. 2021;70(4):1-187.
  4. Mobley V; Seña AC. Mycoplasma genitalium infection in men and women. UpToDate. Last updated February 15, 2019. Accessed September 8, 2021
  5. Kent H. Epidemiology of vaginitis. Am J Obstet Gynecol. 1991;165(4):1168-1176.
  6. Lis R, Rowhani-Rahbar A, Manhart LE. Mycoplasma genitalium infection and female reproductive tract disease: a meta-analysis. Clin Infect Dis 2015;61:418–26. PMID:25900174 https://doi.org/10.1093/ cid/civ312
  7. Gaydos C, et al. Molecular Testing for Mycoplasma genitalium in the United States: Results from the AMES Prospective Multicenter Clinical Study. J Clin Microbiol. 2019;57(11):e01125-19.
  8. LeRoy C, et al. French prospective clinical evaluation of the Aptima Mycoplasma genitalium CE-IVD Assay and Macrolide Resistance Detection Using Three Distinct Assays. J Clin Microbiol. 2017;55(11):3194-3200
  9. Schachter J, et al. Vaginal swabs are the specimens of choice when screening for Chlamydia trachomatis and Neisseria gonorrhoeae: results from a multicenter evaluation of the APTIMA assays for both infections. Sex Transm Dis. 2005;32(12):725-728.
  10. Stafford IA, et al. Retrospective analysis of infection and antimicrobial resistance patterns of Mycoplasma genitalium among pregnant women in the southwestern USA. BMJ Open. 2021;11(6):e050475.
  11. CDC. Antibiotic Resistance Threats in the United States, 2019. Atlanta, GA: U.S. Department of Health and Human Services, CDC; 2019. Available online: www.cdc.gov/DrugResistance/Biggest-Threats.html. DOI: http://dx.doi.org/10.15620/cdc:82532.
  12. Manhart LE, Leipertz G, Soge OO, Jordan SJ, McNeil C, Pathela P, Reno H, Wendel K, Parker A, Geisler WM, Getman D, Golden MR; MyGeniUS Study Team. Mycoplasma genitalium in the US (MyGeniUS): Surveillance Data From Sexual Health Clinics in 4 US Regions. Clin Infect Dis. 2023 Nov 17;77(10):1449-1459. doi: 10.1093/cid/ciad405. PMID: 37402645; PMCID: PMC10654846. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10654846/.
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