Treatment for Ureaplasma and Mycoplasma Infections
Mycoplasma pneumoniae (Respiratory Infections)
Macrolide antibiotics are the first-line treatment for Mycoplasma pneumoniae infections in both children and adults. 1
First-Line Options:
- Azithromycin: 500 mg on day 1, then 250 mg daily for 4 days (5-day total course) is the preferred macrolide due to better tolerability and fewer drug interactions 1
- Clarithromycin: 500 mg twice daily for 7-14 days is an alternative macrolide option 1, 2
- Erythromycin is less commonly used due to significant gastrointestinal intolerance 1, 3
Alternative Options (for macrolide resistance or treatment failure):
- Doxycycline: 100 mg twice daily for 7-14 days (for patients ≥8 years old) 1, 4
- Minocycline: 200 mg loading dose, then 100 mg twice daily for 7-14 days 1
- Fluoroquinolones (adults only):
Critical Monitoring Points:
- Fever resolution typically takes 2-4 days with macrolide therapy for M. pneumoniae—do not assume treatment failure before 48-72 hours 1, 3
- If no improvement after 48-72 hours, consider alternative diagnosis, complications, or macrolide resistance and switch to tetracyclines or fluoroquinolones 1, 3
- Hospitalization is warranted if no improvement after 5 days of appropriate therapy or if condition worsens 1
Age-Specific Considerations:
- Children <5 years: Start with amoxicillin empirically (as S. pneumoniae is more common), but switch to macrolides if M. pneumoniae is specifically suspected 1
- Children ≥5 years: Macrolides are first-line empirical treatment 1
Mycoplasma genitalium and Ureaplasma urealyticum (Genitourinary Infections)
For non-gonococcal urethritis caused by Mycoplasma genitalium or Ureaplasma urealyticum, doxycycline followed by resistance-guided therapy is the recommended approach. 5, 6
First-Line Treatment Strategy:
- Doxycycline: 100 mg twice daily for 7 days as initial therapy 5, 4, 6
- This serves as both treatment and a "resistance test" for subsequent macrolide therapy 6
Subsequent Therapy (Resistance-Guided):
For macrolide-susceptible M. genitalium:
- Azithromycin 2.5 g extended regimen: 1 g on day 1, then 500 mg daily for 3 days achieves 95.4-95.7% cure rate 6
- This extended regimen is superior to single-dose azithromycin 1 g, which has only 91% efficacy and causes macrolide resistance in 100% of treatment failures 7, 8
For macrolide-resistant M. genitalium:
- Moxifloxacin: 400 mg daily for 7 days achieves 92% cure rate 6
- Levofloxacin and ofloxacin are alternatives but were excluded from some guidelines based on parsimony 5
Critical Evidence on Azithromycin Dosing:
- Single-dose azithromycin 1 g should NOT be used as first-line therapy for M. genitalium because it develops macrolide resistance in 100% of treatment failures and has declining efficacy (from 85.3% pre-2009 to 67% post-2009) 5, 7, 8
- The 5-day extended azithromycin regimen (total 1.5 g) has 99% eradication rate and does not select for resistance 8
- Azithromycin should only be used if doxycycline has failed or is contraindicated, or if there are major adherence concerns 5
Treatment Efficacy by Pathogen:
- Doxycycline alone: Only 43% effective for M. genitalium (38% in men, 48% in women), making it inadequate as monotherapy 8, 9
- Ureaplasma urealyticum: Doxycycline is FDA-approved and effective 4
- Chlamydia trachomatis co-infection: Doxycycline 100% effective; azithromycin 97% effective 5
Common Pitfalls to Avoid:
- Do not use single-dose azithromycin 1 g for M. genitalium—this drives macrolide resistance globally 7, 8
- Do not rely on doxycycline monotherapy for M. genitalium—it has unacceptably low cure rates 8, 9
- Test of cure is essential 14-28 days post-treatment to detect treatment failures 6
- De novo macrolide resistance develops in 4.6% of cases even without prior macrolide exposure 6
Special Populations
Mycoplasma Species in Endocarditis (Rare):
- Doxycycline 100 mg twice daily for 4 weeks PLUS gentamicin 3 mg/kg daily IV for 2 weeks 5
- Treatment success expected in ≥90% of cases 5