Can Mycoplasma species (e.g., Mycoplasma genitalium or Mycoplasma hominis) cause pelvic inflammatory disease in sexually active women of reproductive age, and what is the recommended treatment regimen?

Can Mycoplasma Cause PID?

Yes, Mycoplasma genitalium is a recognized pathogen that causes pelvic inflammatory disease (PID) in women, accounting for 15-25% of PID cases, and should be considered alongside Chlamydia trachomatis and Neisseria gonorrhoeae as a causative organism. 1

Evidence for Mycoplasma as a PID Pathogen

Multiple CDC guidelines consistently identify Mycoplasma genitalium as an established cause of cervicitis and PID in women. 1, 2 The organism has been associated with:

• Endometritis with over a 13-fold increased risk in prospective studies 3, 4
• Salpingitis and adnexitis independent of gonococcal and chlamydial infection 4
• Post-termination PID with a sixfold increased risk 3
• Tubal factor infertility based on serologic evidence 3, 4

The role of Mycoplasma hominis and Ureaplasma urealyticum in PID is less clear but possible. 1 CDC guidelines from 1998 state that M. hominis and U. urealyticum "might be etiologic agents of PID," though culture or NAATs for Ureaplasma are not recommended due to high colonization rates in asymptomatic individuals. 1

Clinical Significance and Diagnostic Challenges

Up to 70% of PID cases have no identified etiology when only testing for gonorrhea and chlamydia, making Mycoplasma genitalium an important consideration in culture-negative PID. 3, 4 The organism causes:

• Mucopurulent cervicitis with purulent endocervical discharge 2
• Abnormal vaginal discharge and intermenstrual bleeding 2
• Lower abdominal/pelvic pain with cervical motion tenderness 5

A critical pitfall: Standard PID treatment regimens (cefoxitin plus doxycycline) do not adequately cover M. genitalium, and this organism has been associated with treatment failure when these regimens are used. 3, 4

Diagnostic Approach

Nucleic acid amplification testing (NAAT) is the only acceptable diagnostic method for M. genitalium, as culture is impractical due to slow growth. 2 However, no FDA-cleared commercial NAAT is currently available, though many laboratories have validated molecular assays. 1, 2

Recommended specimens include:

• First-void urine in men 2
• Vaginal swabs (self-collected or provider-collected) in women 2
• Endocervical swabs as acceptable alternatives 2

Treatment Recommendations

When M. genitalium is detected or strongly suspected:

First-line treatment: Azithromycin 500 mg orally on day 1, then 250 mg orally daily on days 2-5 for uncomplicated infection without documented macrolide resistance. 2, 6

For macrolide-resistant M. genitalium or treatment failure: Moxifloxacin 400 mg orally once daily for:

• 7 days for uncomplicated infection 2
• 14 days for complicated infections including PID 2

Critical management requirements:

• All sexual partners within the preceding 60 days must be evaluated and treated simultaneously, regardless of symptoms 2, 6
• Patients must abstain from sexual intercourse until 7 days after completing therapy 2, 6
• Partners must also abstain until completing their own treatment 2, 6

Integration with Standard PID Treatment

For clinically diagnosed PID where M. genitalium testing is unavailable or pending:

Standard outpatient PID regimen (which does NOT adequately cover M. genitalium):

• Ceftriaxone 250 mg IM single dose PLUS
• Doxycycline 100 mg orally twice daily for 14 days PLUS
• Metronidazole 500 mg orally twice daily for 14 days 7

If M. genitalium is subsequently detected or suspected, consider adding or switching to moxifloxacin 400 mg daily for 14 days, especially if symptoms persist after standard therapy. 2

Common Pitfalls to Avoid

• Do not assume standard PID treatment covers M. genitalium—it does not, and treatment failure is common 3, 4
• Do not perform test-of-cure earlier than 3 weeks post-treatment, as false-positives from dead organisms are common 2
• Do not neglect partner treatment—untreated partners are the primary cause of persistent infection and reinfection 2
• Consider repeat testing at 3-6 months due to high reinfection rates, particularly in patients with treatment failure 2, 6

Bottom Line for Clinical Practice

Maintain a high index of suspicion for M. genitalium in sexually active women with PID, especially when:

• Standard PID treatment fails 3, 4
• Testing for gonorrhea and chlamydia is negative 3, 4
• The patient has persistent or recurrent symptoms 2

While M. genitalium testing is not universally available, awareness of this pathogen should influence treatment decisions in culture-negative PID cases and guide empiric therapy selection when standard regimens fail. 1, 2