What is the diagnosis and treatment for Mycobacterium (M.) genitalium infection?

Mycoplasma genitalium: Diagnosis and Treatment

Diagnosis

Nucleic acid amplification testing (NAAT) is the only acceptable diagnostic method for M. genitalium, as culture is impractical due to the organism's slow growth characteristics. 1, 2

Testing Indications

• Test symptomatic patients with urethritis (men) or cervicitis (women) 3
• Test patients with persistent or recurrent non-gonococcal urethritis after standard treatment 1, 3
• Test women with pelvic inflammatory disease (PID) when possible 3, 4
• Consider testing in persistent cervicitis after excluding chlamydia and gonorrhea 1

Specimen Collection

• First-void urine in men 1
• Vaginal swabs (self-collected or provider-collected) in women 1
• Endocervical swabs are acceptable alternatives 1
• Rectal and pharyngeal specimens can be tested but require laboratory validation 1

Critical Diagnostic Requirement

Resistance testing for macrolide resistance mutations must be included with M. genitalium detection, as this directly determines treatment selection. 3 This is essential because macrolide resistance significantly impacts cure rates and treatment decisions.

Diagnostic Limitations

• No FDA-cleared commercial NAAT is currently available 1
• Laboratories must use validated in-house assays with comprehensive internal controls 2
• Standardized diagnostic tests are not commercially available in many settings 1

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Treatment

First-Line Treatment (Macrolide-Susceptible or Unknown Resistance)

Azithromycin 500 mg orally on day 1, then 250 mg orally daily on days 2-5 is the recommended first-line treatment for uncomplicated M. genitalium infection without documented macrolide resistance. 1, 3

• This extended azithromycin regimen achieves 85-95% cure rates in macrolide-susceptible infections 3
• The extended course appears superior to single-dose azithromycin 3
• Some experts recommend doxycycline 100 mg twice daily for 7 days as pre-treatment to decrease organism load and reduce macrolide resistance selection 3

Second-Line Treatment (Macrolide-Resistant or Treatment Failure)

Moxifloxacin 400 mg orally once daily for 7 days (uncomplicated) or 14 days (complicated infections including PID or epididymitis) should be used for macrolide-resistant M. genitalium or after azithromycin failure. 1, 3, 4

• Moxifloxacin currently appears to uniformly eradicate M. genitalium 4
• Use 14-day course for complicated infections (PID, epididymitis) 3
• However, fluoroquinolone resistance is emerging and increasing 3, 5

Third-Line Treatment (Persistent Infection)

For infections persisting after both azithromycin and moxifloxacin 3:

• Doxycycline or minocycline 100 mg orally twice daily for 14 days may cure 40-70% 3
• Pristinamycin 1 g orally four times daily for 10 days has approximately 75% cure rate (where available) 3

Treatment Efficacy Context

• Doxycycline monotherapy has only 30-40% cure rate, though resistance is not increasing 3
• Single-dose azithromycin (1 g) is less effective than extended regimens 3

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Critical Management Considerations

Partner Management

All sexual partners within the preceding 60 days must be evaluated and treated simultaneously, regardless of symptoms. 1, 6 This prevents reinfection and ongoing transmission 7.

Sexual Activity Restrictions

• Patients must abstain from sexual intercourse until 7 days after completing therapy 6
• Partners must also abstain until completing their own treatment course 6

Follow-Up Protocol

• Test of cure is not routinely recommended unless symptoms persist 7
• Patients should return if symptoms persist or recur after treatment 6
• Consider repeat testing at 3-6 months due to high reinfection rates 6

Common Pitfalls to Avoid

• Do not use doxycycline alone as definitive therapy - cure rates are inadequate at 30-40% 3
• Do not use single-dose azithromycin - extended regimens are superior 3
• Do not ignore partner treatment - simultaneous treatment is essential to prevent reinfection 1, 6
• Be aware of increasing antimicrobial resistance - particularly to macrolides and emerging fluoroquinolone resistance 3, 5

Special Populations

• HIV-infected patients receive the same treatment regimens as HIV-negative patients 7
• M. genitalium is recognized as an emerging STI of public health concern requiring partner notification 8

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Clinical Context

M. genitalium causes 10-35% of non-chlamydial non-gonococcal urethritis in men and is associated with cervicitis and PID in 10-25% of women 3, 9. Asymptomatic infections are frequent 3. The organism is transmitted through direct mucosal contact 3.

The narrowing of testing and treatment indications to primarily symptomatic patients reflects concerns about increasing antimicrobial resistance and the need for judicious antibiotic use. 3