What is the recommended testing and treatment protocol for Mycoplasma genitalium (M. genitalium) infection in males?

Testing for Mycoplasma genitalium in Males

For symptomatic males with urethritis, test for M. genitalium using nucleic acid amplification testing (NAAT) on first-void urine or urethral swab, and when available, include macrolide resistance testing to guide appropriate antibiotic therapy. 1, 2, 3

When to Test for M. genitalium

Primary Indications for Testing:

• Persistent or recurrent urethritis after initial treatment with standard NGU regimens (doxycycline or azithromycin) 1, 3
• Symptomatic urethritis with confirmed objective signs (mucopurulent discharge, ≥5 WBCs per oil immersion field on urethral Gram stain, or ≥10 WBCs per high-power field on first-void urine microscopy) 1, 3
• Sexual contacts of patients with confirmed M. genitalium infection 3

When NOT to Test:

• Asymptomatic males without known M. genitalium exposure should not be routinely screened, as this leads to inappropriate antibiotic use and promotes resistance 2, 3, 4
• Initial presentation of urethritis before treating for gonorrhea and chlamydia, unless specific M. genitalium testing is readily available 1

Diagnostic Testing Methods

Specimen Collection:

• First-void urine (preferred for patient comfort and equivalent sensitivity) 2, 3
• Urethral swab (alternative specimen type) 2, 3

Test Type:

• NAAT is the only acceptable diagnostic method for M. genitalium, as culture is impractical and unreliable 2, 3, 5
• Macrolide resistance testing should be performed whenever possible to guide treatment decisions, though FDA-approved resistance tests are not widely available in the United States 2, 3

Clinical Context and Pitfalls

Important Considerations:

• M. genitalium causes 10-35% of non-chlamydial, non-gonococcal urethritis in men 2
• The organism has a longer incubation period than C. trachomatis, and clinical symptoms cannot distinguish M. genitalium from other causes of NGU 4
• Most M. genitalium infections in men are asymptomatic and likely resolve spontaneously without treatment 4

Common Pitfalls to Avoid:

• Do not test asymptomatic men routinely, as this drives unnecessary antibiotic exposure and accelerates resistance development 2, 3
• Do not rely on symptoms alone to diagnose M. genitalium—objective evidence of urethritis must be documented first 1
• Do not assume treatment success without resistance testing, as macrolide resistance is now common (cure rates with azithromycin drop from 85-95% in susceptible infections to much lower rates with resistance) 2

Testing Algorithm:

1. Confirm urethritis objectively (discharge, Gram stain showing ≥5 WBCs/oil immersion field, or urine showing ≥10 WBCs/high-power field) 1
2. Test for gonorrhea and chlamydia first using NAAT 1
3. If initial treatment fails or symptoms persist, then test specifically for M. genitalium with resistance testing if available 1, 3
4. For known M. genitalium contacts, test regardless of symptoms 3

Treatment Implications:

• Testing is critical because doxycycline alone has only 30-40% cure rate for M. genitalium 2
• Azithromycin is more effective (85-95% for susceptible strains), which is why the CDC recommends it over doxycycline for initial NGU treatment when M. genitalium is suspected 6, 1, 2
• Moxifloxacin 400 mg daily for 7 days is recommended for macrolide-resistant infections or as second-line therapy 6, 2, 3