What is the treatment for a sexually active adult patient with positive NAA tests for Mycoplasma genitalium and Ureaplasma spp.?

Treatment for Mycoplasma genitalium and Ureaplasma spp. Co-infection

For this patient with confirmed Mycoplasma genitalium and Ureaplasma spp., treat the M. genitalium infection with azithromycin 500 mg orally on day 1, then 250 mg orally daily on days 2-5, and do not treat the Ureaplasma spp. as routine treatment is not recommended. 1, 2

Primary Treatment: Mycoplasma genitalium

M. genitalium is an established sexually transmitted infection requiring treatment when detected by nucleic acid amplification testing, as it causes urethritis, cervicitis, and pelvic inflammatory disease with significant morbidity if untreated 1, 3, 4.

First-Line Regimen (Without Macrolide Resistance Testing)

• Azithromycin 500 mg orally on day 1, followed by 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 and is superior to single-dose azithromycin 3.
• The extended course decreases organism load and reduces the risk of selecting macrolide resistance mutations 3.

Alternative Regimen if Azithromycin Fails

• Moxifloxacin 400 mg orally once daily for 7 days should be used for macrolide-resistant M. genitalium or after azithromycin treatment failure 1, 3.
• For complicated infections including pelvic inflammatory disease or epididymitis, extend moxifloxacin to 14 days 1, 3.

Ureaplasma spp.: No Treatment Recommended

Routine testing and treatment of Ureaplasma spp. in asymptomatic or symptomatic individuals is not recommended based on current evidence 2.

Rationale for Not Treating Ureaplasma

• Asymptomatic carriage of Ureaplasma is extremely common (40-80% of detected cases represent colonization rather than infection) 2.
• There is no evidence that detecting and treating Ureaplasma does more good than harm in most clinical scenarios 2.
• Ureaplasma urealyticum may be associated with urethritis in men only when present in high bacterial loads, but appropriate evidence for effective treatment regimens is lacking 2.
• Unnecessary antimicrobial treatment promotes resistance in these organisms, true STI pathogens, and the general microbiota 2.

Critical Exception

• If the patient has symptomatic urethritis and traditional STI agents (N. gonorrhoeae, C. trachomatis, M. genitalium, T. vaginalis) have been excluded, only then consider testing for U. urealyticum using quantitative species-specific molecular tests 2.
• Only men with high U. urealyticum loads should be considered for treatment, though optimal regimens remain undefined 2.

Essential Partner Management

All sexual partners within the preceding 60 days must be evaluated and treated simultaneously, regardless of symptoms 1.

• Partners should receive the same M. genitalium treatment regimen to prevent reinfection and ongoing transmission 1.
• Both patient and partners must abstain from sexual intercourse until 7 days after completing therapy 1.
• This is critical because reinfection rates are high without proper partner management 1.

Follow-Up Protocol

• Instruct the patient to return if symptoms persist or recur after completing therapy 1.
• Test of cure is not routinely recommended unless symptoms persist 1.
• Consider repeat testing at 3-6 months due to high reinfection rates, particularly if partner treatment compliance is uncertain 1.

Additional Testing Considerations

• Ensure testing for N. gonorrhoeae and C. trachomatis has been completed, as co-infections are common 5.
• Perform syphilis serology and HIV testing with counseling, as recommended for all patients with sexually transmitted infections 6.

Common Pitfalls to Avoid

• Do not treat Ureaplasma spp. reflexively based solely on positive NAAT results, as this contributes to antimicrobial resistance without proven clinical benefit 2.
• Do not use single-dose azithromycin 1 g for M. genitalium, as the extended 5-day regimen has superior efficacy and reduces resistance selection 1, 3.
• Do not neglect partner treatment, as this is the most common cause of treatment failure and persistent infection 1.
• Avoid multiplex PCR panels that include M. hominis and Ureaplasma spp. alongside traditional STI testing, as detection often leads to unnecessary treatment 2.