Mycoplasma Genitalium: Symptoms, Types, Causes and Treatment

Mycoplasma genitalium (M. genitalium) is a tiny but impactful sexually transmitted bacterium that has gained recognition as a significant cause of urogenital infections in both men and women. While its presence often goes unnoticed due to frequent asymptomatic infections, M. genitalium can lead to a range of health complications, from mild discomfort to serious reproductive health challenges. This article provides a comprehensive overview of the symptoms, types, causes, and treatments of M. genitalium, synthesizing the latest evidence and clinical guidelines.

Symptoms of Mycoplasma Genitalium

Mycoplasma genitalium is notorious for causing silent infections, yet it can also produce a spectrum of symptoms that overlap with other sexually transmitted infections (STIs). Recognizing these symptoms is crucial, as untreated infections may lead to severe complications, especially in women. Here, we summarize the main clinical manifestations of M. genitalium infection.

Gender	Common Symptoms	Complications	Source(s)
Men	Urethritis, dysuria, penile discharge	Epididymitis, prostatitis	1 2 4 5 8 10 11
Women	Vaginal discharge, dysuria, abdominal pain, dyspareunia	Cervicitis, PID, infertility, preterm birth	1 2 4 5 7 8 9 10 11 12
Both	Often asymptomatic	Chronic infection, infertility	1 2 3 4 5 8 11

Table 1: Key Symptoms and Complications of Mycoplasma genitalium Infection

Overview of Clinical Manifestations

M. genitalium can infect the urogenital tract of both men and women. However, the majority of infections may not produce any symptoms, which increases the risk of unknowingly transmitting the bacterium to sexual partners 1 2 4 5.

In Men

• Most Common Presentation: Non-gonococcal urethritis (NGU), characterized by:
  • Dysuria (painful urination)
  • Urethral discharge
• Other Possible Symptoms:
  • Mild discomfort or irritation in the urethra
  • Epididymitis (inflammation of the epididymis) and, less commonly, prostatitis 8 10

In Women

• Most Common Symptoms:
  • Vaginal discharge (often mucopurulent)
  • Dysuria
  • Lower abdominal pain
  • Dyspareunia (pain during intercourse)
• Complications:
  • Cervicitis (inflammation of the cervix)
  • Pelvic inflammatory disease (PID)
  • Increased risk of infertility, preterm birth, and spontaneous abortion 2 5 7 9 11 12

Asymptomatic Cases

A significant proportion of both men and women harbor M. genitalium without noticeable symptoms. Silent infections can persist and contribute to ongoing transmission and complications such as chronic pelvic pain or infertility 1 2 3 4 5.

Complications and Long-term Effects

• Women: Untreated M. genitalium can ascend to the upper genital tract, causing PID, which may result in tubal factor infertility, ectopic pregnancy, and adverse pregnancy outcomes 2 5 7 9 11 12.
• Men: Complications are less frequent but may include chronic urethritis and, rarely, epididymitis or prostatitis 8.

Special Populations

• Men Who Have Sex with Men (MSM): M. genitalium can infect the rectum, often asymptomatically. While rectal infection is common, it is not clearly associated with proctitis symptoms in MSM 3.
• People with HIV: Immunocompromised individuals may experience more severe or persistent infections 8.

Types of Mycoplasma Genitalium

While Mycoplasma genitalium is a single bacterial species, ongoing research has revealed genetic diversity within the bacterium. Understanding these types helps trace infection patterns and may influence treatment strategies as antibiotic resistance becomes more prevalent.

Type Name	Defining Feature	Prevalence/Distribution	Source(s)
mgpB types	Genetic variation in mgpB adhesin gene	43 types identified; 4 most common (types 4, 6, 113, 108)	6
Resistance types	Macrolide and quinolone resistance mutations	High in MSM, increasing globally	3 6 14
Strain diversity	Sequence differences in key genes	Associated with re-infection or persistent infection	6

Table 2: Types and Genetic Diversity of Mycoplasma genitalium

Genetic Typing: mgpB and Other Loci

M. genitalium strains are commonly typed based on sequence variations in the mgpB gene, which encodes an adhesin protein critical for bacterial attachment to host cells. Over 40 mgpB types have been described, with some being more prevalent than others 6.

• mgpB Typing Utility:
  • Tracks transmission dynamics
  • Differentiates between treatment failure (persistence of the same strain) and new infection (different strain)
  • Helps in epidemiological investigations

Resistance Types

A major focus in recent years has been on strains harboring resistance mutations:

• Macrolide Resistance: Mutations in the 23S rRNA gene confer resistance to azithromycin and related antibiotics.
• Quinolone Resistance: Mutations in gyrA, parC, and other genes reduce susceptibility to moxifloxacin and similar drugs.
• Multi-drug Resistant Strains: Increasingly reported, especially in high-risk populations and areas with extensive antibiotic use 3 6 14.

Implications of Strain Diversity

• Re-infection vs. Persistence: Typing allows clinicians to distinguish between persistent infection by the same strain (treatment failure) and re-infection with a new strain, which is common in sexually active individuals 6.
• No Clear Link to Severity: Current evidence does not show a direct correlation between mgpB type and disease severity or resistance profile 6.

Causes of Mycoplasma Genitalium

Understanding the causes and risk factors for M. genitalium infection is essential for both prevention and control. This section explores how the bacterium is transmitted, who is at greatest risk, and what biological mechanisms underpin its pathogenicity.

Cause	Description	Risk Group / Factor	Source(s)
Sexual contact	Direct mucosal exposure (vaginal, anal)	Sexually active individuals, especially with multiple partners	1 2 4 9 11 12
Asymptomatic carriage	No symptoms, still contagious	All infected, especially undiagnosed	1 2 4 5 8
Sperm attachment	Binds to spermatozoa, may aid upper tract infection	Women (risk of PID, infertility)	9
High-risk sexual behavior	Unprotected sex, multiple partners, MSM	Increased prevalence, resistance	1 2 3 4 6 14

Table 3: Causes and Risk Factors for Mycoplasma genitalium Infection

How Is Mycoplasma genitalium Transmitted?

• Sexual Transmission:
  • The bacterium is primarily spread through direct mucosal contact during vaginal or anal intercourse 1 2 4 9 11 12.
  • Oral transmission is not well established.
• Asymptomatic Spread:
  • Many individuals are unaware they are infected, facilitating ongoing transmission within sexual networks 1 2 4 5 8.
• Attachment to Sperm:
  • Remarkably, M. genitalium can bind to human spermatozoa, which may enable the bacteria to reach and infect the upper genital tract in women, potentially leading to infertility or pregnancy complications 9.

Key Risk Factors

• High-Risk Sexual Behavior:
  • Engaging with multiple partners, inconsistent condom use, or belonging to certain populations (e.g., MSM) increases risk 1 2 3 4 14.
• History of Other STIs:
  • Co-infections with Chlamydia trachomatis or Neisseria gonorrhoeae are common 3.
• Geographic Factors:
  • Prevalence rates vary by region and population; some areas and groups (e.g., China, MSM populations) have particularly high rates of infection and antibiotic resistance 3 6 7.

Pathogenesis and Disease Mechanisms

• Adhesion: Specialized proteins allow M. genitalium to stick to urogenital tract cells, evading the host immune system 8 12.
• Inflammatory Response: The bacterium triggers inflammation, leading to tissue damage and symptoms such as discharge or pain 8 12.
• Immune Evasion: M. genitalium’s small genome and lack of a cell wall help it hide from immune defenses and persist in the host, causing chronic or recurrent infections 8 12.

Treatment of Mycoplasma Genitalium

Treating M. genitalium has become increasingly challenging due to rising antibiotic resistance. Effective management now requires tailored approaches based on local resistance patterns, patient populations, and the presence of complications.

Antibiotic	Efficacy (approx.)	Use Case / Indication	Source(s)
Doxycycline	30–40%	First step, reduces bacterial load	1 2 13 14 15 16
Azithromycin (extended)	85–99% (if susceptible)	First-line for susceptible infections	1 2 13 14 15 16
Moxifloxacin	85–100%	Second-line or if macrolide-resistant	1 2 14 16
Pristinamycin	~90%	Third-line, multidrug-resistant cases	1 2 14
Resistance-guided therapy	>92%	Sequential, tailored based on resistance profile	16

Table 4: Treatment Options and Outcomes for Mycoplasma genitalium Infection

Current Treatment Strategies

First-Line Therapy

• Azithromycin (Extended Regimen):
  • 500 mg on day one, then 250 mg daily for 4 days (total 1.5 g) is now preferred over a single 1 g dose due to lower resistance development 1 2 14 15.
  • Cure rates are high (85–99%) in macrolide-susceptible strains 1 2 13 15.
• Doxycycline:
  • 100 mg twice daily for 7–14 days; efficacy is relatively poor (30–40%) but helps reduce bacterial load and may be used as a preliminary step before other antibiotics 1 2 14 15 16.

Second-Line and Resistance-Guided Therapy

• Moxifloxacin:
  • 400 mg once daily for 7–10 days; used when macrolide resistance is detected or after azithromycin failure 1 2 14 16.
  • Resistance to moxifloxacin is increasing; resistance testing is recommended where available 14 16.
• Resistance-Guided Sequential Treatment:
  • Begin with doxycycline, then use resistance testing to determine whether to prescribe azithromycin or a fluoroquinolone (e.g., moxifloxacin, sitafloxacin). This approach achieves cure rates above 92% 16.

Third-Line and Alternative Options

• Pristinamycin:
  • 1 g four times daily for 10 days; effective in multidrug-resistant infections but not widely available 1 2 14.
• Other Agents:
  • Josamycin, solithromycin, and sitafloxacin are being studied or used in certain regions 1 2 14.

Challenges: Antibiotic Resistance

• Macrolide Resistance:
  • Global rates are rising, largely due to overuse of single-dose azithromycin and lack of test-of-cure protocols 13 14 15.
• Quinolone Resistance:
  • Increasing, especially in high-risk populations 14.
• Multidrug Resistance:
  • Cases with resistance to both macrolides and fluoroquinolones are emerging, making infections difficult to treat 14.

Treatment of Complicated Infections

• Pelvic Inflammatory Disease (PID), Epididymitis:
  • Moxifloxacin for 14 days is recommended for upper genital tract infections 1 2.

Best Practices

• Test of Cure: Always perform a repeat nucleic acid amplification test (NAAT) 3–4 weeks after treatment to confirm eradication.
• Resistance Testing: Whenever possible, utilize NAAT-based resistance assays to guide antibiotic choice 1 2 14 16.
• Partner Management: Treat sexual partners simultaneously to prevent reinfection 1 2.

Conclusion

Mycoplasma genitalium is a challenging, often silent, sexually transmitted pathogen that has significant implications for sexual and reproductive health. Its rising resistance to standard antibiotics makes diagnosis and management increasingly complex. Awareness, timely testing, and evidence-based therapeutic strategies are essential to curb its impact.

Summary of Key Points:

• Symptoms:

  • Frequently asymptomatic; when present, symptoms include urethritis in men and cervicitis or PID in women.
  • Complications can include infertility and adverse pregnancy outcomes.

• Types:

  • Genetic diversity exists, with multiple mgpB types identified.
  • Resistance-associated strains are increasingly common.

• Causes:

  • Sexually transmitted via direct mucosal contact.
  • High-risk sexual behaviors and asymptomatic carriage drive spread.

• Treatment:

  • Extended azithromycin regimens preferred for susceptible infections.
  • Resistance-guided therapy and second-line fluoroquinolones (e.g., moxifloxacin) for resistant cases.
  • Rising multidrug resistance highlights the need for careful antibiotic stewardship and new treatment options.

By staying informed and vigilant, both healthcare providers and sexually active individuals can help limit the spread and complications of Mycoplasma genitalium.