Genital Mycoplasmas

Mycoplasmas, the smallest self-replicating organisms, are commonly found in the genitourinary tract.¹ However, they are occasionally found outside this environment, usually in immunocompromised people.¹ Among the 6 genital mycoplasmas located in the genitourinary tract, 4 (Mycoplasma hominis, M genitalium, Ureaplasma parvum, and U urealyticum) cause clinical infection.¹

Genital Mycoplasma Cause & Presentation

Genital mycoplasmas caused by both Mycoplasma and Ureaplasma species are sexually transmitted; however, their role in genital tract disease varies significantly.¹ 

U urealyticum and M genitalium cause acute and persistent nongonococcal urethritis (NGU), with M genitalium being the second leading cause of NGU after Chlamydia trachomatis.^1,2 Although M hominis and U parvum are found in the male genital tract, neither are causative pathogens of NGU.^1,2 Clinical manifestations of mycoplasmas in men are similar regardless of the underlying pathogen, with symptoms including dysuria, irritation, urgency, meatal pruritus, and urethral discharge.^1,3 Evidence of an etiologic role for mycoplasmas in urethritis in women is lacking; however, M hominis and U urealyticum are loosely associated with this condition.⁴

M genitalium causes endocervicitis, as evidenced by cervical tenderness, abnormal vaginal discharge, and/or intermenstrual bleeding.^1,3 However, more than half of women who test positive for M genitalium are asymptomatic.³ In addition, M genitalium and to a lesser extent M hominis and Ureaplasma species are associated with pelvic inflammatory disease (PID).¹ 

When M hominis is present in vaginal fluid, it is strongly associated with bacterial vaginosis.¹ Vaginal discharge with or without a fishy odor is a common complaint, but a portion of individuals are asymptomatic.⁵ In genitourinary tract syndromes such as PID, the contribution of M hominis to symptoms remains unclear.¹

High levels of M hominis in the vagina strongly correlate with shedding of HIV and may be a risk factor for transmission of the virus.¹ Urogenital infection with M genitalium has been found to be associated with increased HIV shedding, especially in patients not undergoing treatment with antiretroviral therapy.⁶ In addition, M genitalium can cause rectal infections (most of which are asymptomatic), with 1% to 26% of cases occurring in men who have sex with men and 3% of cases occurring in women.⁶ 

Genital mycoplasmas can cause systemic infections, most often presenting as sepsis syndrome, and M hominis is the most common associated pathogen.¹ Postoperative wound infections, postpartum fever, and septic arthritis caused by M hominis are well documented, and cases of endocarditis, pneumonia, and abscesses have also been reported.¹ 

Diagnostic Workup & Physical Examination

Clinical evaluation based on patient presentation and history should include a pelvic examination, if necessary, and sampling of vaginal or penile discharge, first-void urine, and/or rectal and endocervical swabs.^3,5 

The following clinical situations lead to a higher degree of suspicion for genital mycoplasmas as the causative agent:

• Pyelonephritis with negative standard cultures and failed antibiotic treatment⁴
• Persistent symptoms of lower urinary tract infection⁴
• Recurrent or persistent NGU in men testing negative for infections with C trachomatis⁷
• Symptoms of cervicitis with negative test results for bacterial vaginosis and trichomoniasis⁷
• Culture-negative cases of well-documented infection with properly collected samples in the absence of antibiotic treatment¹

Genital mycoplasmas are frequently identified using culture systems; however, this screening modality is time-consuming. Ureaplasma species and M hominis require 2 to 5 days to grow, and M genitalium can takes up to 8 weeks to grow.⁶ Culturing, especially for M genitalium, has therefore lost popularity owing to the development of newer technologies for the diagnosis of sexually transmitted infections (STIs).²

Nucleic acid amplification tests (NAATs) are the gold standard for identification of STIs.^2,6 They are more sensitive than other diagnostic methods such as culture, nucleic acid hybridization, or antigen detection tests.^2,9 NAAT is noninvasive, requiring a vaginal swab or first-void urine sample.²

Use of multiplex real-time polymerase chain reaction (RT-PCR) assays has made it easier for clinicians to test for more than 1 causative organism. These newer assays — which have improved detection sensitivity, decreased amplification time, and lowered labor and reagent costs compared with conventional PCR — are cost effective.² Authors of a study that examined the sensitivity and specificity of RT-PCR assays in the detection of STIs showed RT-PCRs to be 100% sensitive and specific for M genitalium.² 

Another benefit to NAATs is that they can distinguish between the Ureaplasma species U urealyticum and U parvum.^2,9 The results of a 2018 study revealed that approximately 5% of women of childbearing age are colonized with U urealyticum compared with approximately 30% who are colonized with U parvum.⁹ Distinguishing between these 2 species prevents unnecessary treatment of U parvum, which is more of a colonizing pathogen than a causative one.² Some diagnostic testing kits may not be able to distinguish between Ureaplasma species, necessitating additional testing.²

Differential Diagnosis of Genital Mycoplasmas

The symptomatology of genital mycoplasma infections is similar to that of infection with other sexually transmitted pathogens, such as C trachomatis and Neisseria gonorrhoeae). For this reason, NAATs are essential for making an accurate diagnosis.² In men with symptoms of urethritis, clinicians should consider chronic prostatitis or chronic pelvic pain syndrome as potential causes.⁷ Bacterial or yeast infections should also be ruled out.⁸

Risks & Complications

In men, infection with M genitalium has been linked to chronic complications such as prostatitis, epididymitis, and infertility; however, there are insufficient data to establish this pathogen as causative.⁶ Authors of a large meta-analysis reported that the prevalence of U urealyticum and M hominis was higher among infertile men compared with fertile men.¹⁰ There is also evidence to suggest that infection with U urealyticum affects sperm quality.²

Women with M genitalium infection have a 2-fold increased risk for spontaneous abortion, preterm delivery, infertility, cervicitis, and PID.⁶ Results of a meta-analysis revealed a higher prevalence of U urealyticum, M hominis, and M genitalium in infertile women compared with fertile women.¹⁰

Although the evidence is mixed, there appears to be a link between pregnancy complications —such as premature rupture of membranes (PROM), spontaneous abortion, and preterm delivery — and colonization with U urealyticum and M hominis.⁸ Colonization with M hominis has been associated with higher rates of PROM compared with colonization with U urealyticum.¹¹ Detection of U urealyticum in vaginal cultures has been linked to chorioamnionitis.⁸ Infection with U urealyticum alone or coinfection with Candida has been reported to increase the risk of chorioamnionitis and preterm birth before 30 weeks.⁸ 

An increased level of proinflammatory biomarkers in the amniotic fluid has also been linked to adverse pregnancy outcomes; this increase was associated with M hominis and U urealyticum but not M genitalium.¹¹ Neonates are frequently colonized with Ureaplasma species and less frequently M hominis in both the genital and respiratory tracts after vaginal birth.¹ The primary risk factor for colonization is exposure to vaginal secretion at birth,  and female infants are more likely to be colonized than male infants.¹ 

Despite the abundance of evidence regarding risks and complications associated with M genitalium, long-term effects of asymptomatic infection among men and women are unknown.⁶ 

References

1. Martin DH. Genital mycoplasmas: Mycoplasma genitalium, Mycoplasma hominis, and Ureaplasma species. In: Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 9th ed. Elsevier; 2020:2340-2343. 

2. Choe HS, Lee DS, Lee SJ, et al. Performance of Anyplex ™ II multiplex real time PCR for the diagnosis of seven sexually transmitted infections: comparison with currently available methods. Int J Infect Dis. 2013;17:E1134-E1140. doi:10.1016/j.ijid.2013.07.011 

3. Ona S, Molina RL, Diouf K. Mycoplasma genitalium: an overlooked sexually transmitted pathogen in women? Infect Dis Obstet Gynecol. 2016;2016:4513089. doi:10.1155/2016/4513089

4. Combaz-Sohnchen N, Kuhn A. A systematic review of mycoplasma and ureaplasma in urogynaecology. Geburtshilfe Frauenheilkd. 2017;77(12):1299-1303. doi:10.1055/s-0043-119687

5. Abou Chacra L, Fenollar F, Diop K. Bacterial vaginosis: what do we currently know? Front Cell Infect Microbiol. 2022;11:672429. doi:10.3389/fcimb.2021.672429

6. Mycoplasma genitalium – STI Treatment Guidelines, 2021. Centers for Disease Control and Prevention. Reviewed July 22, 2021. Accessed November 21, 2022. https://www.cdc.gov/std/treatment-guidelines/mycoplasmagenitalium.htm

7. Diseases characterized by urethritis and cervicitis – STI Treatment Guidelines, 2021. Centers for Disease Control and Prevention. Reviewed September 22, 2022. Accessed November 21, 2022. https://www.cdc.gov/std/treatment-guidelines/urethritis-and-cervicitis.htm 

8. Matasariu DR, Ursache A, Agache A, et al. Genital infection with Ureaplasma urealyticum and its effect on pregnancy. Exp Ther Med. 2022;23(1):89. doi:10.3892/etm.2021.11012

9. Leli C, Mencacci A, Latino MA, et al. Prevalence of cervical colonization by Ureaplasma parvum, Ureaplasma urealyticum, Mycoplasma hominis and Mycoplasma genitalium in childbearing age women by a commercially available multiplex real-time PCR: an Italian observational multicentre study. J Microbiol Immunol Infect. 2018;51(2):220-225. doi:10.1016/j.jmii.2017.05.004

10. Moridi K, Hemmaty M, Azimian A, Fallah MH, Khaneghahi Abyaneh H, Ghazvini K. Epidemiology of genital infections caused by Mycoplasma hominis, M. genitalium and Ureaplasma urealyticum in Iran; a systematic review and meta-analysis study (2000–2019). BMC Public Health. 2020;20(1):1020. doi:10.1186/s12889-020-08962-5 

11. Noda-Nicolau NM, Tantengco OAG, Polettini J, et al. Genital mycoplasmas and biomarkers of inflammation and their association with spontaneous preterm birth and preterm prelabor rupture of membranes: a systematic review and meta-analysis. Front Microbiol. 2022;13:859732. doi:10.3389/fmicb.2022.859732

Author Bio

Emilie White, PharmD, is a clinical pharmacist with more than a decade of experience providing direct patient care in a hospital setting. She received her Doctor of Pharmacy degree from Massachusetts College of Pharmacy and Health Sciences. After graduation, she completed a postgraduate pharmacy residency. Her background includes caring for critical care, internal medicine, and surgical patients.