Short answer

M.

genitalium (Mgen) testing is targeted molecular diagnostics for a specific clinical situation: symptoms persisting after standard chlamydia/gonorrhea workups and treatment.

Only Mgen-specific NAAT detects it, routine panels are blind to it by design, and testing is increasingly paired with resistance-marker assays that direct therapy away from antibiotics that will fail.

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When testing is warranted. And when it is not

Order Mgen testing for symptoms persisting after chlamydia/gonorrhea treatment (ongoing discharge, burning, pelvic pain), recurrent urethritis or cervicitis, PID with negative standard workups, and partners of confirmed Mgen cases.

Do not order it for asymptomatic screening. Guidance is explicit here, because indiscriminate testing drives macrolide resistance without clinical benefit.

This restraint is the opposite of most STI logic (where broader screening helps) and exists because Mgen treatment options are narrow and resistance is already widespread.

Assay landscape. Availability and resistance markers

FDA-authorized Mgen NAAT assays now exist alongside lab-developed tests, but availability still concentrates in reference laboratories and larger health systems. Smaller clinics send out rather than testing in-house, adding days to turnaround.

Resistance-marker assays detecting 23S rRNA mutations predict macrolide (azithromycin) failure before treatment starts and reroute therapy to alternatives per current guidance.

Ask whether your laboratory reports resistance markers with the NAAT result; the combined report changes management, the NAAT alone only starts the conversation.

Sampling. Same samples, specific requisition

First-catch urine, vaginal or endocervical swabs, and rectal swabs by exposure site. Mirroring chlamydia sampling exactly, but run through Mgen-specific requisitions that must be ordered deliberately.

Standard NAAT orders do not reflex to Mgen.

Test-of-cure follows treatment where guidance advises, timed to avoid dead-DNA positives.

For window and retest timing principles, see STI Testing Window Periods Explained.

Interpreting results. Context decides treatment

  • Positives in persistent-symptom contexts get resistance-guided therapy per current CDC guidance. The result explains the persistence.
  • Positives without symptoms generally do not trigger treatment (avoiding resistance pressure on a limited drug arsenal).
  • Negatives redirect the workup toward trichomoniasis, urinary causes, or non-infectious conditions rather than broader antibiotics.

Either way, partners of confirmed cases need evaluation, and abstinence runs through resolution.

When to seek care

For symptoms surviving first-line STI therapy, recurrent urethritis/cervicitis, PID with negative standard panels, and partner Mgen diagnoses.