What antibiotic is recommended for treating urinary tract infections (UTIs) caused by Mycoplasma genitalium and Mycoplasma hominis?

Treatment of UTI Caused by Mycoplasma genitalium and Mycoplasma hominis

First-Line Treatment Recommendation

For Mycoplasma genitalium urinary tract infections, use azithromycin 500 mg on day 1, followed by 250 mg daily on days 2-5 (extended regimen), which achieves 93-99% cure rates while minimizing macrolide resistance development. 1

For Mycoplasma hominis, doxycycline 100 mg orally twice daily for 7 days is the preferred treatment, as this organism is naturally resistant to macrolides. 2

Treatment Algorithm by Pathogen

Mycoplasma genitalium

Initial therapy (macrolide-susceptible or unknown resistance status):

• Azithromycin 500 mg orally on day 1, then 250 mg daily on days 2-5 1, 3
• This extended regimen is superior to the single 1g dose, which has declining efficacy (dropped from 85% pre-2009 to 67% post-2009) 2

Second-line therapy (macrolide-resistant or treatment failure):

• Moxifloxacin 400 mg orally once daily for 7 days for uncomplicated infections 3
• Moxifloxacin 400 mg orally once daily for 14 days for complicated infections (epididymitis, pelvic inflammatory disease) 3
• Note: Moxifloxacin cure rates have declined from 100% pre-2010 to 89% post-2010 due to emerging fluoroquinolone resistance 4

Third-line therapy (persistent infection after both azithromycin and moxifloxacin):

• Doxycycline 100 mg orally twice daily for 14 days (40-70% cure rate) 3
• Pristinamycin 1g orally four times daily for 10 days (~75% cure rate) 3

Mycoplasma hominis

First-line therapy:

• Doxycycline 100 mg orally twice daily for 7 days 2
• M. hominis lacks the 23S rRNA target for macrolides, making azithromycin ineffective 2

Alternative regimens:

• Ofloxacin 300 mg orally twice daily for 7 days 2
• Levofloxacin 500 mg orally once daily for 7 days 2

Critical Clinical Considerations

Resistance Testing

• When available, test for macrolide resistance mutations in M. genitalium before treatment to guide therapy 3
• The presence of 23S rRNA gene mutations strongly predicts azithromycin treatment failure 5
• Azithromycin MICs >8 μg/ml correlate with microbiologic failure in 100% of cases (18/18 patients), while MICs <0.004 μg/ml fail in only 8% (1/12 patients) 6

Why Doxycycline Alone is Inadequate for M. genitalium

• Doxycycline monotherapy achieves only 30-40% cure rates for M. genitalium 1, 3, 5
• Doxycycline MICs (range 0.125-2 μg/ml) show no correlation with treatment outcomes 6
• However, doxycycline resistance is not increasing, unlike macrolide and fluoroquinolone resistance 3

Partner Management and Follow-Up

• Patients must abstain from sexual intercourse for 7 days after single-dose therapy or until completion of multi-day regimens 1, 2
• All sexual partners within the preceding 60 days require evaluation and treatment to prevent reinfection 2
• Test for co-infections including gonorrhea, chlamydia, syphilis, and HIV 2, 7
• Return for evaluation only if symptoms persist or recur after treatment completion 2, 7

Common Pitfalls to Avoid

Do not use single-dose azithromycin 1g for M. genitalium: The extended 5-day regimen is more effective and reduces resistance selection 1, 3

Do not use azithromycin for M. hominis: This organism is intrinsically resistant to macrolides 2

Do not use moxifloxacin as first-line without resistance testing: Reserve fluoroquinolones for macrolide-resistant cases or treatment failures to preserve efficacy 3

Do not retreat based on symptoms alone: Require objective evidence of urethritis (≥10 WBC per high-power field on urine microscopy or positive leukocyte esterase) before re-treatment 2

Avoid empiric treatment without confirmation: While the 2006 CDC guidelines suggest azithromycin may work better for M. genitalium 2, the more recent 2021 European guideline emphasizes the importance of resistance-guided therapy given rising resistance rates 3