When should a test of cure be performed for Mycoplasma genitalium infection?

Test of Cure for Mycoplasma genitalium Infection

Test of cure is not routinely recommended for Mycoplasma genitalium infection, but if performed, must be delayed until at least 3-4 weeks after completing treatment to avoid false-positive results from residual dead organisms. 1, 2

When Test of Cure Should Be Performed

Symptomatic patients only: Test of cure should be reserved for patients whose symptoms persist or recur after completing the full treatment course. 1

Specific Clinical Scenarios Requiring Test of Cure:

• Persistent urethral discharge, dysuria, or pelvic pain after completing azithromycin or moxifloxacin therapy 1
• Questionable treatment adherence when you suspect the patient did not complete the full antibiotic course 1
• Complicated infections (pelvic inflammatory disease or epididymitis) where treatment failure carries higher morbidity risk 3, 4

Critical Timing Requirements

Wait at least 3-4 weeks after treatment completion before testing. 1, 2

Why This Timing Matters:

• M. genitalium PCR becomes negative within 8 days in 96% of macrolide-susceptible infections treated with azithromycin 2
• However, dead bacterial DNA persists and will trigger false-positive NAAT results if tested too early 1, 2
• In one study, patients who were successfully treated showed negative PCR within 1 week for moxifloxacin and within 8 days for azithromycin, but testing at these early timepoints would have been unreliable 2

What to Do Instead of Routine Test of Cure

Reinfection screening at 3-6 months is more clinically valuable than test of cure. 1

The Reinfection Problem:

• Most post-treatment M. genitalium infections result from reinfection by untreated partners, not treatment failure 1
• Reinfection rates are high because partners often remain untreated or patients resume sexual activity within high-prevalence networks 1
• All sexual partners from the preceding 60 days must be treated simultaneously to prevent this cycle 1, 3, 4

Sexual Abstinence Requirements

Patients must abstain from all sexual intercourse for 7 days after completing therapy AND until all partners have also completed treatment. 1

This dual requirement addresses both:

• Adequate time for bacterial clearance in the index patient 1
• Prevention of immediate reinfection from untreated partners 1

Common Pitfalls to Avoid

Do not test earlier than 3 weeks post-treatment – you will get false-positives from residual DNA of dead organisms, leading to unnecessary retreatment and further antibiotic resistance. 1, 2

Do not assume partners were treated – directly verify partner treatment or use expedited partner therapy, because untreated partners are the primary cause of persistent infection. 1

Do not retreat based on symptoms alone without objective evidence – require documentation of M. genitalium by NAAT before administering additional antibiotics, as symptoms may be from other causes. 1

Special Consideration: Macrolide Resistance Development

One concerning finding is that macrolide-resistant strains can emerge after an initial 10-day period of negative tests following azithromycin treatment. 2

• In 4 patients with initially susceptible strains, resistance mutations appeared after treatment despite negative interim tests 2
• This phenomenon occurred with both extended azithromycin (1.5g over 5 days) and single-dose azithromycin (1g) 2
• This supports delaying test of cure to 3-4 weeks, as earlier testing might miss these late-emerging resistant strains 2

HIV-Infected Patients

HIV-positive patients receive identical treatment regimens and follow the same test-of-cure recommendations as HIV-negative patients. 1