Diagnosis and Treatment of Mycoplasma genitalium in Women
Direct Recommendation
When macrolide-resistance testing is unavailable, treat suspected M. genitalium cervicitis or pelvic pain with doxycycline 100 mg orally twice daily for 7 days followed immediately by azithromycin 500 mg on day 1, then 250 mg daily on days 2-5. 1, 2, 3
Diagnostic Approach
When to Test for M. genitalium
Test women with mucopurulent cervicitis characterized by purulent endocervical exudate or sustained cervical bleeding induced by gentle swabbing, as M. genitalium is strongly associated with these findings (adjusted OR 4.38). 4, 5
Test women with persistent or recurrent cervicitis after standard chlamydia/gonorrhea treatment has failed, as M. genitalium accounts for 10-25% of cervicitis cases. 1, 2
Test women with pelvic inflammatory disease, as M. genitalium is an established cause of PID. 1, 2, 6
Do not routinely test asymptomatic women or those with non-specific vaginal discharge alone, as M. genitalium prevalence is similar in symptomatic (7%) and asymptomatic (5%) women and is not associated with common genital symptoms. 5
Diagnostic Testing Method
Nucleic acid amplification testing (NAAT) is the only acceptable diagnostic method for M. genitalium, as culture is impractical due to slow growth. 1, 7
Collect vaginal swabs (self-collected or provider-collected) as the preferred specimen type in women; endocervical swabs are acceptable alternatives. 1
No FDA-cleared commercial NAAT is currently available for M. genitalium in the United States, limiting testing availability in many clinical settings. 1
Concurrent Testing Required
Perform NAATs for C. trachomatis and N. gonorrhoeae on all women with cervicitis, as these remain the most common identifiable causes. 4, 8
Conduct wet-mount microscopy to assess for ≥10 WBC per high-power field and to detect Trichomonas vaginalis. 4
Perform syphilis and HIV testing for every patient diagnosed with a new sexually transmitted infection. 4
Treatment Strategy Without Resistance Testing
First-Line Sequential Therapy
The optimal approach when macrolide-resistance testing is unavailable is sequential therapy starting with doxycycline:
Doxycycline 100 mg orally twice daily for 7 days reduces bacterial load by a mean 2.60 log10, which decreases the risk of selecting macrolide resistance during subsequent azithromycin treatment. 2, 3
Immediately follow with azithromycin 500 mg orally on day 1, then 250 mg orally daily on days 2-5 (extended 5-day regimen), which achieves 85-95% cure rates in macrolide-susceptible infections and has higher efficacy than single-dose azithromycin. 1, 2, 3
This sequential approach cured ≥92% of infections in a prospective study and selected macrolide resistance in only 2.6% of cases, compared to much higher rates with azithromycin monotherapy. 3
Rationale for Sequential Therapy
Macrolide resistance is present in 48-68% of M. genitalium infections in recent studies, making empiric azithromycin monotherapy increasingly problematic. 2, 3, 5
Doxycycline alone has only 30-40% cure rates but serves as effective pre-treatment to reduce organism load before azithromycin. 2, 3
The extended 5-day azithromycin regimen (2.5 g total) has superior efficacy compared to the 1 g single-dose regimen historically used. 2, 3
When to Add Gonococcal Coverage
- Add ceftriaxone 500 mg IM single dose when local N. gonorrhoeae prevalence exceeds 5% or in high-risk settings (age <25 years, new or multiple partners, unprotected intercourse). 4
Management of Treatment Failure
Second-Line Therapy
Moxifloxacin 400 mg orally once daily for 7 days for uncomplicated infections that persist after azithromycin-based therapy. 1, 2, 6
Moxifloxacin 400 mg orally once daily for 14 days for complicated infections including PID or when symptoms suggest upper genital tract involvement. 1, 2
Moxifloxacin currently achieves the most uniform eradication of M. genitalium, but quinolone resistance is increasing. 2, 6
Before Prescribing Second-Line Therapy
Re-evaluate for reinfection from untreated partners, as this accounts for most post-treatment infections, not treatment failure. 1
Verify that all sexual partners from the preceding 60 days have been treated, as untreated partners are the primary cause of persistent infection. 1
Reassess for other causes of persistent cervicitis including chemical irritants, douching, abnormal vaginal flora, or idiopathic inflammation in the ectopy zone. 4, 8
Partner Management (Critical for Success)
All sexual partners within the preceding 60 days must be notified, examined, and treated with the same regimen as the index patient, regardless of symptoms. 4, 1
Partners should receive the full sequential doxycycline-azithromycin regimen even if asymptomatic, as asymptomatic infections are frequent. 1, 2
Both patient and partners must abstain from sexual intercourse until 7 days after completing the full treatment course. 4, 1
Reinfection from untreated partners is the most common cause of persistent infection, not antimicrobial resistance or treatment failure. 1
Follow-Up Protocol
Instruct patients to return if symptoms persist or recur after completing therapy. 4, 1
Test of cure is not routinely recommended unless symptoms persist, but consider repeat testing at 3-6 months due to high reinfection rates. 1
If performing test of cure, wait at least 3 weeks after treatment completion to avoid false-positive results from dead organisms. 1
Repeat infections confer elevated risk for PID and complications compared to initial infection, making reinfection prevention critical. 1
Critical Pitfalls to Avoid
Do not use single-dose azithromycin 1 g monotherapy for suspected M. genitalium, as this has unacceptably high failure rates (15-50%) and selects for macrolide resistance. 2, 3
Do not continue empiric antibiotics indefinitely for persistent cervicitis without an identified pathogen, as this has no proven benefit. 4
Do not test or treat based solely on non-specific vaginal discharge, as M. genitalium is not associated with this symptom and testing is not indicated. 5
Do not perform test of cure earlier than 3 weeks post-treatment, as false-positives from dead organisms are common. 1
Do not overlook partner treatment, as this is the most common reason for apparent treatment failure. 1