MG, the new and dangerous sexually transmitted disease

Mycoplasma genitalium (MG) is an increasingly recognized cause of genitourinary infection. Although identified in the 1980s, MG has come to prominence over the past decade because of improved diagnostic methods, expanding prevalence data, and rising rates of antimicrobial resistance. MG can cause symptomatic and asymptomatic infection in both women and men and has been associated with cervicitis, urethritis and pelvic inflammatory disease (PID). It is now considered an important pathogen in sexually transmitted infection (STI) practice and public health planning.

This article reviews the clinical features, diagnosis, treatment, prevention and public health implications of MG using current evidence and professional guidance. Information is framed for patients and clinicians and cites major medical organizations and clinical resources (ACOG, NIH, Mayo Clinic, Cleveland Clinic).

What is Mycoplasma genitalium?

Mycoplasma genitalium is a small, slow-growing bacterium that lacks a cell wall and is adapted to colonize the mucosa of the urogenital tract. Because it lacks a cell wall, MG is intrinsically resistant to antibiotics that target cell wall synthesis (for example, beta-lactams). The organism is fragile outside the host and is typically transmitted through sexual contact.

MG was first isolated in the early 1980s but was historically difficult to detect because it grows slowly and requires specialized laboratory techniques. The advent of nucleic acid amplification tests (NAATs, such as polymerase chain reaction, PCR) greatly improved the ability to detect MG and has revealed that the organism is more common than previously recognized in many settings (ACOG; NIH).

How is MG transmitted?

MG is transmitted primarily through sexual activity that involves mucosal contact (genital-genital, and possibly oral-genital or anal-genital contact). It colonizes the urethra in men and the cervix and endometrium in women, and it can be present in the rectum. Transmission risk increases with unprotected sexual contact and with multiple sexual partners.

Because MG may be asymptomatic, individuals can transmit the organism without awareness of infection. Condom use reduces but does not eliminate transmission risk. There is not yet an effective vaccine to prevent MG (Mayo Clinic; Cleveland Clinic; NIH).

Epidemiology and burden

Prevalence estimates vary by population and geography. In low-risk general populations, MG prevalence is generally reported in the low single digits, while higher rates are observed in STI clinic populations and among men who have sex with men (MSM). The organism is an important recognized cause of nongonococcal urethritis (NGU) in men and is increasingly implicated in cervicitis and PID among women.

A key concern is the emergence and spread of antibiotic-resistant strains, particularly those resistant to macrolides (e.g., azithromycin) and, in some cases, to fluoroquinolones (e.g., moxifloxacin). Antimicrobial resistance complicates treatment, increases the risk of persistent infection, and raises public health concerns (NIH; ACOG).

Microbiology and pathogenesis

Mycoplasma genitalium belongs to the Mycoplasma genus, a group of bacteria characterized by small genome size and absence of a cell wall. MG adheres to epithelial cells of the urogenital tract via specialized adhesins and can cause localized inflammation. The organism is able to persist in the mucosa and evade host defenses, contributing to chronic or recurrent symptoms in some patients.

Infection may produce an inflammatory response leading to urethritis in men and cervicitis and ascending infection (endometritis, salpingitis) in women. Persistent or untreated infection in women has been associated in some studies with pelvic inflammatory disease and possible adverse reproductive outcomes, though research is ongoing to better quantify these risks (ACOG; NIH).

Clinical manifestations

MG infection can be asymptomatic or symptomatic. Symptoms are often similar to those caused by other urogenital pathogens and therefore require diagnostic testing for differentiation.

In men

Urethritis: the most common clinical manifestation. Symptoms may include dysuria (discomfort with urination), urethral discharge, or urethral irritation.
Epididymitis: less commonly, MG may be associated with inflammation of the epididymis leading to scrotal pain and swelling.
Asymptomatic colonization: many men have no symptoms but can still transmit infection.

In women

Cervicitis: signs can include abnormal vaginal discharge, cervical inflammation observed on pelvic exam, and intermenstrual or postcoital bleeding.
Pelvic inflammatory disease (PID): ascending infection may cause endometritis, salpingitis and tubal inflammation; PID can result in pelvic pain, fever and potential reproductive sequelae.
Pregnancy outcomes: studies have explored associations between MG and preterm birth or spontaneous abortion, but the evidence is not yet conclusive and research continues.
Asymptomatic infection: a substantial proportion of women may be asymptomatic.

Incubation and symptom timing

The incubation period is variable; symptoms, when they occur, can appear days to months after exposure. MG may persist for extended periods if not treated or if treatment fails due to resistance.

Complications

PID, with potential for tubal factor infertility, ectopic pregnancy risk and chronic pelvic pain.
Persistent or recurrent urethritis.
Possible adverse pregnancy outcomes (under investigation).
Treatment failure due to antimicrobial resistance, leading to chronic symptoms and ongoing transmission.

Diagnosis

Accurate diagnosis of MG relies on laboratory testing. Because clinical manifestations overlap with other STIs (for example, Chlamydia trachomatis and Neisseria gonorrhoeae), laboratory confirmation is essential.

Tests

Nucleic acid amplification tests (NAATs): the preferred method for MG detection. NAATs are more sensitive and specific than culture. Specimens can include first-void urine (in men), vaginal swabs, endocervical swabs (in women) and rectal swabs when indicated by exposure history.
Culture: possible but rarely used clinically because MG is difficult to culture and culture methods are slow and specialized.
Antimicrobial resistance testing: molecular assays that detect mutations associated with macrolide resistance (23S rRNA mutations) and fluoroquinolone resistance (parC/gyrA) are increasingly available and are important for guiding therapy when accessible.

Not all clinical laboratories offer MG testing or resistance testing. Clinicians should consult local laboratory capabilities and follow national guidance for specimen collection and testing indications (ACOG; Mayo Clinic; Cleveland Clinic).

Who should be tested?

Testing strategies vary by guideline and clinical context. Consider testing individuals who:

Are symptomatic with urethritis, cervicitis or PID when standard pathogens have been excluded or when symptoms persist despite standard therapy.
Have persistent or recurrent NGU after treatment for other causes.
Have sexual partners known to be infected with MG.
Are in high-prevalence settings or at high risk (for example, STI clinic attendees or some MSM populations), according to local public health guidance.

Routine screening of asymptomatic persons in the general population is not universally recommended; decisions should follow local or national STI guidelines and clinical judgment (ACOG; NIH).

Test-of-cure

Because of resistance and treatment failure risk, a test-of-cure (repeat NAAT) is often recommended in certain situations. Timing of test-of-cure varies by regimen used; many experts recommend performing a test-of-cure approximately 3–4 weeks after completion of therapy or per local guideline recommendations. If treatment included macrolides and resistance testing was not performed, earlier evaluation of persistent symptoms is advised (CDC guidance and ACOG resources provide more details).

Treatment

Treatment of MG is complicated by evolving resistance patterns. Historically, macrolide antibiotics (e.g., azithromycin) were commonly used; however, macrolide resistance has become widespread in many regions, reducing efficacy. Fluoroquinolones (e.g., moxifloxacin) have activity against many macrolide-resistant strains, but fluoroquinolone resistance has also been reported.

Because of these issues, current practice increasingly emphasizes resistance-guided therapy: testing for macrolide resistance-associated mutations to help select appropriate antibiotics and reduce the risk of treatment failure.

General treatment principles

Use NAAT for diagnosis when clinical suspicion exists.
If available, perform resistance testing to guide therapy.
If macrolide resistance is known or suspected, alternative regimens such as moxifloxacin are often recommended.
Doxycycline has limited efficacy against MG but may be used as part of sequential or combination strategies in resistance-guided approaches.
Follow national or local STI treatment guidelines; consult infectious disease or sexual health specialists when infections are complicated or resistant.

Example regimens and resistance-guided approach

Note: Specific drug choices and dosing should follow the most recent clinical guidelines and local resistance patterns. The following summarizes commonly discussed approaches rather than prescriptive orders.

Resistance-guided therapy (recommended where available):
If NAAT shows MG and macrolide-susceptible genotype: macrolide therapy (for example, azithromycin in an extended regimen) may be effective.
If macrolide-resistance detected: use a fluoroquinolone (commonly moxifloxacin) or an alternative regimen per guideline.
Empiric therapy in settings without resistance testing:
Some clinicians use a doxycycline course followed by moxifloxacin for persistent or proven infection.
Empiric azithromycin use is less favored in many regions because of high macrolide resistance rates.

Because MG treatment options and resistance patterns evolve, clinicians should consult current guidance from professional organizations (such as ACOG and local public health authorities) and the most recent STI treatment guidelines when selecting therapy (ACOG; NIH; Mayo Clinic).

Special considerations

Pregnancy: management is complex because some recommended agents (for example, fluoroquinolones) are generally avoided in pregnancy due to potential fetal risk; consultation with obstetrics/infectious disease specialists and review of up-to-date guidance are recommended. The balance between treating symptomatic infection and potential drug risks must be individualized.
Fluoroquinolone intolerance or resistance: when resistance to both macrolides and fluoroquinolones exists or when patients cannot take these drugs, options are limited and expert consultation is advised.
Test-of-cure: recommended in many circumstances because of treatment failure risk; timing depends on regimen and guidelines.

Management of sexual partners

Sexual partners of persons diagnosed with MG should be notified, evaluated and treated according to public health guidance.
Partners should abstain from sexual activity with the index patient until both have completed therapy and symptoms resolve (or until test-of-cure confirms eradication), to prevent reinfection.
Partner management recommendations vary; clinicians should follow local STI partner management policies and provide counseling on testing, treatment and prevention.

Prevention

There is no vaccine for MG. Prevention strategies align with general STI prevention principles:

Consistent and correct condom use reduces risk by limiting mucosal contact.
Reducing the number of sexual partners and engaging in mutually monogamous relationships where both partners are tested can decrease risk.
Routine STI screening according to risk and guideline recommendations helps early detection and treatment.
Prompt evaluation and treatment of symptoms or known exposures reduces the likelihood of complications and transmission.
Open communication with sexual partners and timely partner notification are essential to interrupt transmission chains.

Public health surveillance, access to reliable diagnostic testing and antimicrobial stewardship (avoiding unnecessary antibiotic exposure that can drive resistance) are also key elements of prevention at the population level (NIH; ACOG; Cleveland Clinic).

Special populations

Pregnancy

MG in pregnancy requires careful consideration. Some antibiotics commonly used to treat MG are not recommended in pregnancy; therefore, clinicians must weigh potential risks and benefits and may involve obstetric infectious disease specialists. The association between MG and adverse pregnancy outcomes is under active study; current evidence does not definitively define the magnitude of risk. Pregnant individuals with symptomatic infection or PID should be evaluated and managed per specialist recommendations (ACOG; NIH).

Men who have sex with men (MSM)

MG has been detected among MSM, including in the rectum and urethra. Rectal infection may be asymptomatic. Screening and testing strategies should be informed by sexual exposure history and local epidemiology.

Adolescents

Adolescent patients are at risk for STI and should receive age-appropriate counseling, confidential testing and treatment when indicated. Education on prevention and access to care are particularly important in this group.

Public health concerns and antimicrobial resistance

Antimicrobial resistance in MG is a major public health concern. Macrolide resistance-associated mutations are common in many regions, and fluoroquinolone resistance is emerging. The spread of multi-drug–resistant MG strains threatens treatment efficacy and increases the risk of persistent infection, complications and ongoing transmission.

Public health responses include:

Improved access to diagnostic NAATs and resistance testing.
Resistance-guided treatment algorithms to limit the use of ineffective antibiotics.
Surveillance programs to monitor prevalence and resistance trends.
Research into new therapeutics and potential vaccines.
Provider and patient education to promote appropriate testing, treatment and partner management (NIH; ACOG).

Research and future directions

Ongoing research priorities include:

Development of rapid point-of-care NAATs and resistance assays to enable immediate resistance-guided therapy.
New antibiotic agents and combination regimens effective against resistant MG strains.
Improved understanding of the role of MG in adverse reproductive outcomes, including infertility and pregnancy complications.
Vaccine research, although this remains in early stages.
Public health strategies to slow the spread of resistance and improve detection in high-risk populations.

Advances in diagnostics and therapeutics are essential to manage MG as resistance evolves.

When to seek care

Seek medical evaluation if you experience symptoms such as urethral discharge, pelvic pain, abnormal vaginal discharge, bleeding with intercourse, or persistent genitourinary discomfort. Also seek testing after known exposure to an infected partner. Timely evaluation, testing and appropriate treatment reduce the risk of complications and limit transmission to partners.

If you have been treated for MG and symptoms persist, contact your healthcare provider for re-evaluation and possible repeat testing and resistance assessment.

Key points for clinicians and patients

MG is a recognized cause of urethritis, cervicitis and PID and may be asymptomatic.
NAAT is the diagnostic standard; resistance testing (macrolide and fluoroquinolone-associated mutations) improves therapeutic decision-making.
Antimicrobial resistance, especially to macrolides, complicates treatment; resistance-guided therapy is increasingly recommended.
Partner notification and treatment are essential to prevent reinfection.
Preventive measures include condom use, reducing the number of sexual partners and timely testing after exposure.
Pregnant persons, individuals with persistent symptoms, and those with multidrug-resistant infections should receive specialist consultation.

For clinical management, follow current national and local STI treatment guidelines and consult infectious disease or sexual health specialists for complex or resistant cases.

References and resources

American College of Obstetricians and Gynecologists (ACOG). Clinical guidance on sexually transmitted infections and related resources. Available at: https://www.acog.org/ (consult specific ACOG committee opinions and practice bulletins for up-to-date recommendations).
National Institutes of Health (NIH) / National Institute of Allergy and Infectious Diseases (NIAID). Research and information on Mycoplasma genitalium, antimicrobial resistance and STI research priorities. https://www.niaid.nih.gov/
Mayo Clinic. Mycoplasma genitalium: Overview, symptoms, diagnosis and treatment. https://www.mayoclinic.org/
Cleveland Clinic. Mycoplasma genitalium: Patient education and clinical summary. https://my.clevelandclinic.org/
Centers for Disease Control and Prevention (CDC). Sexually transmitted infections treatment guidelines and resources (for guidance on STI diagnosis and management). https://www.cdc.gov/std/

(Consult the most current versions of professional society guidelines and national public health recommendations for specific diagnostic and therapeutic algorithms, dosing regimens and management of special populations.)