What is the recommended dose of Azithromycin (macrolide antibiotic) for the treatment of gonorrhea?

Azithromycin Dosing for Gonorrhea Treatment

Azithromycin should NOT be used as monotherapy for gonorrhea; the recommended dose is 1 g orally as a single dose in combination with ceftriaxone 250 mg intramuscularly, or 2 g orally as a single dose only in patients with severe cephalosporin allergy (with mandatory test-of-cure). 1, 2

Primary Treatment Regimen

Dual therapy is the standard of care for uncomplicated gonococcal infections of the cervix, urethra, rectum, and pharynx:

• Ceftriaxone 250 mg IM (single dose) PLUS azithromycin 1 g orally (single dose) 3, 1
• Azithromycin is preferred over doxycycline due to single-dose convenience, better compliance, and substantially lower gonococcal resistance rates compared to tetracycline 3, 1
• This dual therapy approach improves treatment efficacy and delays emergence of cephalosporin resistance by using two antimicrobials with different mechanisms of action 3, 1

Alternative Regimens When Ceftriaxone Is Unavailable

If ceftriaxone cannot be obtained:

• Cefixime 400 mg orally (single dose) PLUS azithromycin 1 g orally (single dose) 3, 4
• Critical caveat: Cefixime provides lower and less sustained bactericidal levels than ceftriaxone and has limited efficacy for pharyngeal gonorrhea 3
• Mandatory test-of-cure at 1 week is required with this regimen 3, 4

Severe Cephalosporin Allergy

For patients who cannot receive any cephalosporin:

• Azithromycin 2 g orally as a single dose 3, 1, 2
• Mandatory test-of-cure at 1 week 3, 4
• This is the ONLY scenario where azithromycin monotherapy is acceptable 1

Critical Pitfalls to Avoid

• Never use azithromycin 1 g as monotherapy—efficacy is only 93-96.5%, which is insufficient 1, 5, 6
• Never use azithromycin 2 g routinely—reserve this dose exclusively for cephalosporin-allergic patients due to high gastrointestinal side effects (35.3% of patients, with 2.9% experiencing severe symptoms) 7
• Azithromycin resistance is geographically variable and increasing, with some regions showing up to 66% resistance rates 3
• Rising azithromycin MICs (≥8 µg/mL) have been documented, though still uncommon in most areas 8

Rationale for Dual Therapy

The combination approach addresses multiple clinical imperatives:

• Antimicrobial resistance: Rising cefixime MICs and declining effectiveness necessitate combination therapy 3, 1
• Chlamydial co-infection: 40-50% of gonorrhea patients have concurrent chlamydia, making dual coverage essential 1
• Resistance prevention: Dual therapy with different mechanisms of action delays emergence of cephalosporin resistance 3

Site-Specific Considerations

• Pharyngeal gonorrhea is more difficult to eradicate than urogenital or anorectal infections 1, 4
• Ceftriaxone has superior efficacy for pharyngeal infections compared to all oral alternatives 3, 1
• Azithromycin 2 g cured 46/47 (97.9%) oropharyngeal infections in clinical trials 5

Special Populations

• Pregnant women: Use ceftriaxone-based regimens; quinolones and tetracyclines are contraindicated 1, 4
• Men who have sex with men (MSM): Use only ceftriaxone-based regimens due to higher prevalence of resistant strains 1, 4
• Recent foreign travel: Use only ceftriaxone-based regimens 1

Test-of-Cure Requirements

Test-of-cure is NOT routinely needed for standard dual therapy (ceftriaxone + azithromycin) 4. However, it is mandatory in these situations:

• Any alternative regimen (cefixime-based or azithromycin 2 g monotherapy) 3, 4
• Persistent symptoms after treatment 1, 4
• Perform at 1 week post-treatment, ideally with culture or NAAT 3