What is the recommended first‑line treatment for uncomplicated genital Chlamydia trachomatis infection in non‑pregnant adults, and what are the preferred regimens for pregnant or lactating patients and for patients who cannot take doxycycline?

Chlamydia Treatment

For uncomplicated genital chlamydia in non-pregnant adults, treat with either azithromycin 1 g orally as a single dose or doxycycline 100 mg orally twice daily for 7 days—both achieve 97-98% cure rates and are equally effective first-line options. 1, 2

First-Line Treatment Selection

The choice between azithromycin and doxycycline depends on specific clinical circumstances:

Azithromycin 1 g single dose is preferred when:

• Compliance with a 7-day regimen is questionable 3
• Follow-up is unpredictable 3
• Directly observed therapy is needed 3
• The patient is a young adult or from a population with erratic health-care-seeking behavior 3
• Single-dose administration eliminates adherence concerns entirely 1

Doxycycline 100 mg twice daily for 7 days is preferred when:

• Cost is a primary concern, as doxycycline is significantly less expensive 3
• The patient can reliably complete a 7-day course 3
• The infection is rectal—doxycycline shows superior efficacy (94% cure) compared to azithromycin (85% cure) for anorectal chlamydia 1

Alternative once-daily doxycycline formulation: Doxycycline hyclate delayed-release 200 mg once daily for 7 days achieves equivalent 95.5% cure rates with fewer gastrointestinal side effects (13% nausea vs 21% with standard dosing). 1

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Treatment During Pregnancy

Azithromycin 1 g orally as a single dose is the preferred treatment during pregnancy. 3, 1, 2

Alternative regimens for pregnant patients:

• Amoxicillin 500 mg orally three times daily for 7 days 3, 1
• Erythromycin base 500 mg orally four times daily for 7 days (if azithromycin cannot be tolerated) 3, 1

Absolute contraindications in pregnancy:

• Doxycycline 3, 1, 2
• Ofloxacin 3, 1
• Levofloxacin 3, 1
• All fluoroquinolones 3, 1
• Erythromycin estolate (causes drug-related hepatotoxicity) 1

Critical pregnancy-specific requirement:

Mandatory test-of-cure 3-4 weeks after treatment completion in all pregnant patients, preferably by culture, due to lower efficacy of alternative regimens and high rates of gastrointestinal side effects reducing compliance. 3, 1, 2

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Alternative Regimens (When First-Line Options Cannot Be Used)

Use these only when azithromycin and doxycycline are contraindicated:

• Levofloxacin 500 mg orally once daily for 7 days (88-94% efficacy vs 97-98% for first-line agents) 3, 1, 2
• Ofloxacin 300 mg orally twice daily for 7 days 3, 1, 2
• Erythromycin base 500 mg orally four times daily for 7 days 3, 1
• Erythromycin ethylsuccinate 800 mg orally four times daily for 7 days 3, 1

Important caveat: Erythromycin is less efficacious than azithromycin or doxycycline and causes frequent gastrointestinal side effects that reduce compliance. 3, 1

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Pediatric Dosing

Children ≥8 years weighing >45 kg:

• Azithromycin 1 g orally as a single dose OR
• Doxycycline 100 mg orally twice daily for 7 days 3, 1, 2

Children <45 kg:

• Erythromycin base or ethylsuccinate 50 mg/kg/day orally divided into four doses daily for 14 days 3, 1, 2

Neonates with chlamydial conjunctivitis or pneumonia (1-3 months):

• Erythromycin base or ethylsuccinate 50 mg/kg/day orally divided into four doses daily for 14 days (approximately 80% effective; may require second course) 3, 1

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Critical Management Steps

Sexual abstinence requirements:

• Patients must abstain from all sexual intercourse for 7 days after initiating treatment 3, 1, 2
• Abstinence must continue until all sex partners have completed treatment 3, 1, 2

Partner management:

• All sex partners from the preceding 60 days must be evaluated, tested, and empirically treated 3, 1, 2
• Treat the most recent partner even if last sexual contact was >60 days ago 3, 1
• Failing to treat partners leads to reinfection in up to 20% of cases 3, 2

Medication dispensing:

• Dispense medications on-site when possible 3, 1
• Directly observe the first dose to maximize compliance 3, 1

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Follow-Up and Retesting

Test-of-cure (NOT routinely recommended):

• Do NOT perform test-of-cure in non-pregnant patients treated with recommended regimens, as treatment failure rates are extremely low (0-3% in males, 0-8% in females) 3, 2
• Wait at least 3 weeks after treatment before testing if needed, as earlier testing yields false-positives from dead organism DNA 3

Reinfection screening (MANDATORY):

• All women with chlamydia should be retested approximately 3 months after treatment, regardless of whether partners were reportedly treated 3, 1, 2
• Reinfection rates reach 39% in some adolescent populations 3, 1, 2
• Repeat infections carry elevated risk for pelvic inflammatory disease and complications 3, 1, 2

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Common Pitfalls to Avoid

• Do NOT use erythromycin estolate in pregnancy—it causes hepatotoxicity 1
• Do NOT omit test-of-cure in pregnant patients—it is mandatory 1
• Do NOT assume partners were treated—directly verify or use expedited partner therapy 1
• Do NOT perform test-of-cure before 3 weeks—nucleic acid tests detect dead organism DNA, not active infection 3
• Do NOT use fluoroquinolones or tetracyclines during pregnancy—teratogenic risk 3, 1