What is the preferred treatment between doxycycline (DOXY) and azithromycin (AZY) for chlamydia?

Doxycycline vs Azithromycin for Chlamydia

Both doxycycline 100 mg orally twice daily for 7 days and azithromycin 1 g orally as a single dose are equally effective first-line treatments for uncomplicated genital chlamydia, with cure rates of 97-98%, but doxycycline is superior for rectal chlamydia and costs less, while azithromycin offers the advantage of single-dose directly observed therapy when compliance is uncertain. 1, 2, 3

Treatment Selection Algorithm

For Uncomplicated Genital Chlamydia

Choose doxycycline 100 mg orally twice daily for 7 days when:

• Patient compliance with 7-day regimen is reliable 1, 3
• Cost is a primary concern (doxycycline is significantly less expensive) 3
• Patient has rectal infection (see below) 4, 5
• Patient is not pregnant 2, 3

Choose azithromycin 1 g orally as a single dose when:

• Compliance with multi-day regimens is questionable 1, 2, 3
• Follow-up is unpredictable or patient has erratic health-care-seeking behavior 1, 3
• Directly observed therapy is needed 1, 2, 3
• Patient is pregnant (azithromycin is preferred) 2, 3

For Rectal Chlamydia

Doxycycline 100 mg orally twice daily for 7 days is strongly preferred over azithromycin for rectal chlamydia. 4, 5

• A 2021 randomized controlled trial demonstrated doxycycline achieved 96.9% cure rate versus 76.4% for azithromycin in asymptomatic rectal chlamydia among men who have sex with men (risk difference 19.9 percentage points, P<0.001) 4
• Meta-analysis of 2,457 patients confirmed doxycycline's superiority for rectal infection (risk ratio 1.21,95% CI 1.15-1.28) 5

Critical Management Requirements

All patients must:

• Abstain from all sexual intercourse for 7 days after initiating treatment AND until all sex partners complete treatment 1, 2, 3
• Have all sex partners from the preceding 60 days evaluated, tested, and empirically treated 2, 3
• Receive medication dispensed on-site with directly observed first dose when possible 1, 2, 3

Common Pitfalls to Avoid

Reinfection is the primary cause of treatment "failure" (84-92% of recurrent cases), not antibiotic resistance:

• Failure to treat sex partners leads to reinfection in up to 20% of cases 3, 6
• Patients who resume sexual activity before partner treatment completion have high reinfection risk 3, 6
• True treatment failure rates are extremely low: 0-3% in men, 0-8% in women 6

Do not perform test-of-cure before 3 weeks post-treatment:

• Testing before 3 weeks yields false-positives due to dead organisms 1, 2, 3, 6
• Test-of-cure is not recommended for non-pregnant patients treated with recommended regimens unless compliance is questionable, symptoms persist, or reinfection is suspected 1, 2, 3

Do retest all women at 3 months post-treatment:

• This screens for reinfection, not treatment failure 1, 2, 3
• Repeat infections carry elevated risk for pelvic inflammatory disease and complications 2, 3
• Reinfection rates reach 39% in some adolescent populations 2

Special Populations

Pregnancy:

• Azithromycin 1 g orally as a single dose is preferred 2, 3
• Alternative: amoxicillin 500 mg orally three times daily for 7 days 2, 3
• Doxycycline is absolutely contraindicated in pregnancy 2, 3
• Test-of-cure is mandatory 3 weeks after treatment completion 3, 6

Children ≥8 years weighing >45 kg:

• Use adult dosing: azithromycin 1 g single dose or doxycycline 100 mg twice daily for 7 days 2, 3

Coinfection with gonorrhea:

• Always treat for chlamydia when gonorrhea is confirmed due to high coinfection rates 1, 2, 6
• If gonorrhea is present and only chlamydia is treated, symptoms will persist 6

Alternative Regimens

When first-line options cannot be used:

• Erythromycin base 500 mg orally four times daily for 7 days 1, 2
• Ofloxacin 300 mg orally twice daily for 7 days 1, 2
• Levofloxacin 500 mg orally once daily for 7 days 1, 2, 6

Note: Erythromycin is less efficacious than doxycycline or azithromycin, with gastrointestinal side effects that discourage compliance 1, 2