By: Casey N. Pinto PhD, CRNP, MPH, The Pennsylvania State University, Department of Public health Sciences

       Chlamydia was discovered in 1907 but was not associated with non-gonococcal urethritis (NGU) until the 1970s. In 1988 the CDC made chlamydia a nationally notifiable disease in the US. In 1990 there were 34,000 cases documented,^1,2 rising to nearly 1.6 million cases in 2020.³ Prevalence rates of chlamydia among the general population is 2.3%⁴ however, rates vary between 1.4% and 14% based on select social determinants and age.^2,5,6

       Mycoplasma genitalium (MG) was discovered in 1981 during a search for causative agents of NGU.^7,8 However, since the MG bacteria took six months to grow on very specific culture mediums, clinical diagnosis was limited to clinical suspicion. The first assay for MG was approved by the FDA in the US in 2019,⁹ allowing for improved diagnosis and prevalence estimates. Current prevalence of MG is 1% among the general US population⁴ with a range of 4-38% among select population groups.^10-14 Thus MG is more prevalent than gonorrhea (0.4%),⁴ and is quickly catching chlamydia, and surpassing in select populations.

       Initial symptoms of MG are mild (urethritis/cervicitis/proctitis) with limited information on long-term effects. Existing evidence is predominantly among women (endometritis, pelvic inflammatory disease, preterm birth, fetal demise, and infertility).^15-17 Among men it is theorized that infertility, epididymitis, and/or prostatitis are potential long-term effects.^18,19

       MG screening guidelines are continually adjusted based on new evidence. Currently, screening is limited to patients who are symptomatic and includes urine, vaginal, meatal, rectal, and endocervical sites as indicated.¹⁹ Asymptomatic screening should not include MG ¹⁹ unless clinical decision making justifies screening (i.e. partner positive and unable to clear infection). Symptomatic patients who test positive for MG require treatment. Asymptomatic patients with a positive MG test should be considered for treatment based on clinical judgement, especially since there is evidence that 93% of patients will clear an MG infection without any treatment at 12 months.²⁰

       Treatment for MG initially mirrored chlamydia treatment (azithromycin 1gm PO) however, increasing macrolide resistance has been documented among MG isolates (44%-90%).¹⁹ Due to the high rate of macrolide resistance, and the lack of resistance testing in the US (currently available in other countries),²¹ azithromycin should be avoided as a treatment for proven or suspected MG. The current recommendations are doxycycline 100mg PO BID x 7days followed by moxifloxacin 400mg PO daily x 7 days. Doxycycline alone will not adequately treat the infection but will decrease the bacteria burden. So moxifloxacin can successfully eradicate the infection without increasing the rate of resistance among fluoroquinolones.²² While the 7-day doxycycline treatment followed by moxifloxacin is cumbersome, it does allow time for MG testing results to determine if the second antibiotic is needed. Additionally, when resistance testing is available in the US, the 7-day doxycycline window will allow time to determine the appropriate second antibiotic.

       MG is not only likely to be the next chlamydia, but the high likelihood of developing resistance will complicate current and future treatment. Providers should be suspicious of MG in cases of NGU to ensure appropriate and timely treatment.

References

1. Taylor-Robinson D. The discovery of Chlamydia trachomatis. Sex Transm Infect. 2017;93:10.
2. Miller WC. Prevalence of Chlamydial and Gonococcal Infections Among Young Adults in the United States. JAMA. 2004;291(18):2229.
3. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2020. 2021.
4. Manhart LE, Holmes KK, Hughes JP, Houston LS, Totten PA. Mycoplasma genitalium Among Young Adults in the United States: An Emerging Sexually Transmitted Infection. American Journal of Public Health. 2007;97(6):1118-1125.
5. Torrone EAP, John; Weinstock, Hillard. Prevalence of Chlamydia trachomatis Genital Infection Among Persons Aged 14-39 years — United States, 2007-2012. Morbidity and Mortality Weekly Report. 2014;63(38):834-838.
6. Force USPST. Final Recommendation Statement: Chlamydia and Gonorrhea: Screening – US Preventive Services Task Force. In:2019.
7. Tully JG, Taylor-Robinson, David., Cole, Roger M., Rose, David L.,. A Newly Discovered Mycoplasma in the Human Urogenital Tract. The Lancet. 1981:1288-1291.
8. Taylor-Robinson D, Tully, J.G., Furr, P.M., Cole, R.M., Rose, D. L., Hanna, N.F.,. Urogenital mycoplasma infections of man: a review with ovservations on a recently discovered mycoplasma. Isr J Med Sci. 1981;17(7):524-530.
9. FDA permits marketing of first test to aid in the diagnosis of a sexually-transmitted infection known as Mycoplasma genitalium [press release]. 2019.
10. le Roux MCH, Anwar Ahmed. Quantitative Real-Time Polymerase Chain Reaction for the Diagnosis of Mycoplasma genitalium Infection in South African Men With and Without Symptoms of Urethritis. Sex Transm Dis. 2017;144:18-21.
11. Munson E, Wenten D, Jhansale S, et al. Expansion of Comprehensive Screening of Male Sexually Transmitted Infection Clinic Attendees with Mycoplasma genitalium and Trichomonas vaginalis Molecular Assessment: a Retrospective Analysis. Journal of Clinical Microbiology. 2017;55(1):321-325.
12. Getman DJ, A., O’Donnell, Meghan., Cohen, Seth. 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.
13. Seña AC, Lee JY, Schwebke J, et al. A Silent Epidemic: The Prevalence, Incidence and Persistence of Mycoplasma genitalium Among Young, Asymptomatic High-Risk Women in the United States. Clinical Infectious Diseases. 2018;67(1):73-79.
14. Hancock EB, Manhart LE, Nelson SJ, Kerani R, Wroblewski JKH, Totten PA. Comprehensive Assessment of Sociodemographic and Behavioral Risk Factors for Mycoplasma genitalium Infection in Women. Sexually Transmitted Diseases. 2010;37(12):777-783.
15. Frenzer C, Egli-Gany D, Vallely LM, Vallely AJ, Low N. Adverse pregnancy and perinatal outcomes associated with <i>Mycoplasma genitalium:</i> systematic review and meta-analysis. Sex Transm Infect. 2022;98(3):222-227.
16. Cazanave C, Manhart L. E., Bebear, C. Mycoplasma genitalium, an emerging sexually transmitted pathogen. Medecine et Maladies Infectieuses. 2012;42(9):381-392.
17. Vazquez F, Fernández J. Pelvic Inflammatory Disease Due to <i>Mycoplasma genitalium</i>: A Character in Search of an Author. Clinical Infectious Diseases. 2020;71(10):2723-2725.
18. Ahmadi MHM, Akbar; Gilani, Mohammad Ali Sadighi; Bahador, Abbas; Talebi, Malihe Improvement of semen parameters after antibiotic therapy in asymptomatic infertile men infected with Mycoplasma genitalium. Infection. 2018;46:31-38.
19. Centers for Disease Control and Prevention. Sexually Transmitted Infections Treatment Guidelines, 2021. Morbidity and Mortality Weekly Report. 2021;70(4):1-187.
20. Vandepitte J, Weiss HA, Kyakuwa N, et al. Natural history of Mycoplasma genitalium Infection in a Cohort of Female Sex Workers in Kampala, Uganda. Sexually Transmitted Diseases. 2013;40(5):422-427.
21. Manhart LE. Editorial Commentary: Diagnostic and Resistance Testing for Mycoplasma genitalium: What Will It Take? Clinical Infectious Diseases. 2014;59(1):31-33.
22. Pond MJ, Nori AV, Witney AA, Lopeman RC, Butcher PD, Sadiq ST. High Prevalence of Antibiotic-Resistant Mycoplasma genitalium in Nongonococcal Urethritis: The Need for Routine Testing and the Inadequacy of Current Treatment Options. Clinical Infectious Diseases. 2014;58(5):631-637.