What is the recommended treatment for Mycoplasma and Ureaplasma infections?

Treatment of Mycoplasma and Ureaplasma Infections

Ureaplasma urealyticum Treatment

Doxycycline 100 mg orally twice daily for 7 days is the first-line treatment for Ureaplasma urealyticum infections, as recommended by the European Urology guidelines and CDC. 1, 2, 3

First-Line Options:

• Doxycycline 100 mg orally twice daily for 7 days is the most effective first-line treatment with superior efficacy compared to alternatives 1, 4, 3
• Azithromycin 1.0-1.5 g orally as a single dose serves as an alternative when compliance with a 7-day regimen is questionable 1, 2, 5

Alternative Regimens:

• Erythromycin base 500 mg orally four times daily for 7 days if doxycycline is contraindicated 1, 2
• Levofloxacin 500 mg orally once daily for 7 days 2, 4
• Ofloxacin 300 mg orally twice daily for 7 days 2

Management of Treatment Failure:

• After first-line doxycycline failure, use azithromycin 500 mg orally on day 1, followed by 250 mg daily for 4 days 2, 4
• After first-line azithromycin failure, use moxifloxacin 400 mg orally once daily for 7-14 days 2, 4, 6
• For persistent urethritis after doxycycline, extended erythromycin therapy (500 mg four times daily for 14 days) addresses possible tetracycline-resistant strains 1

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Mycoplasma genitalium Treatment

Azithromycin 500 mg orally on day 1, followed by 250 mg orally daily for 4 days (extended 5-day regimen) is the preferred first-line treatment for Mycoplasma genitalium, NOT the single 1 g dose. 1, 7

Critical Evidence on Azithromycin Dosing:

The extended 5-day azithromycin regimen is superior to the 1 g single dose based on multiple lines of evidence:

• Treatment failure rate with azithromycin 1 g single dose is 13.9%, with 12.0% developing macrolide resistance mutations 7
• The extended 5-day regimen has only 3.7% treatment failure rate and significantly lower resistance development 7
• A Swedish study showed 99% eradication with extended azithromycin versus 91% with 1 g single dose 8
• Critically, 100% of patients who failed azithromycin 1 g developed macrolide resistance, while NONE who received extended dosing developed resistance 8

First-Line Treatment:

• Azithromycin 500 mg orally on day 1, followed by 250 mg orally daily for 4 days (total 1.5 g over 5 days) 1, 8, 7

Alternative for Macrolide-Resistant M. genitalium:

• Moxifloxacin 400 mg orally daily for 7-14 days is the treatment of choice for macrolide-resistant strains 1, 6, 9
• Moxifloxacin achieved 100% cure rate in patients who failed azithromycin or ofloxacin 9

Doxycycline Inefficacy:

• Doxycycline should NOT be used for M. genitalium - eradication rate is only 43% overall (38% in men, 48% in women) 8
• Doxycycline failure rate was 55% compared to 13% with azithromycin in head-to-head comparison 10
• Multiple studies confirm doxycycline is inefficient for M. genitalium eradication 8, 10, 11

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Diagnostic and Management Approach

Pre-Treatment Testing:

• Perform validated nucleic acid amplification test (NAAT) on first-void urine or urethral swab before empirical treatment 1
• Consider resistance testing when available, particularly for M. genitalium given rising macrolide resistance rates (increased from 0% in 2006-2007 to 18% in 2011) 8

Test of Cure:

• Test of cure is NOT routinely recommended after doxycycline or azithromycin unless symptoms persist or reinfection is suspected 2
• If performed, test of cure should be done no earlier than 3 weeks after completion of therapy 2
• Consider test of cure when therapeutic compliance is questionable 2

Partner Management:

• Treat all sexual partners with last contact within 60 days of diagnosis 1, 2, 4
• Both patients and partners must abstain from sexual intercourse for 7 days after single-dose therapy or until completion of 7-day regimen 2, 4
• Sexual partners should be referred for evaluation and treatment while maintaining patient confidentiality 1, 2

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Common Pitfalls to Avoid

Critical Errors:

• Do NOT use azithromycin 1 g single dose for M. genitalium - this drives macrolide resistance and has high failure rates 8, 7
• Do NOT use doxycycline for M. genitalium - it is ineffective with <50% cure rates 8, 10
• Do NOT assume treatment failure at 48 hours with macrolides - clinical response may take 2-4 days 1
• Do NOT initiate additional antimicrobial therapy without objective signs of persistent infection 2

Resistance Considerations:

• Macrolide resistance in M. genitalium is increasing globally and is strongly associated with azithromycin 1 g single-dose regimens 8, 11, 7
• Fluoroquinolone resistance is emerging, with first cases of moxifloxacin failure due to multidrug-resistant M. genitalium reported 11
• Suboptimal macrolide dosing (1 g single dose) is the primary driver of resistance emergence 11, 7