What is the first‑line therapy for uncomplicated genital Chlamydia trachomatis infection in non‑pregnant adults, and what are the alternative regimens for pregnant patients, lymphogranuloma venereum, and when doxycycline or azithromycin are contraindicated?

Treatment of Chlamydia

For uncomplicated genital chlamydia in non-pregnant adults, use 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 for Non-Pregnant Adults

Choose between two equally effective regimens:

• Azithromycin 1 g orally, single dose achieves 97% microbial cure 1, 2, 3

  • Preferred when compliance is uncertain because it allows directly observed therapy 1, 2
  • Better for populations with erratic health-care-seeking behavior 1
  • More expensive but cost-effective when follow-up is unpredictable 1

• Doxycycline 100 mg orally twice daily for exactly 7 days achieves 98% microbial cure 4, 1, 2

  • Lower cost with extensive clinical experience 1, 2
  • Alternative once-daily formulation: Doxycycline delayed-release 200 mg once daily for 7 days has equivalent 95.5% efficacy with less nausea (13% vs 21%) and vomiting (8% vs 12%) 4
  • Superior for rectal chlamydia: Doxycycline shows 94-100% cure vs 79-87% for azithromycin in MSM with anorectal infection 4, 1

Critical implementation: Dispense medication on-site and directly observe the first dose to maximize compliance 1, 2

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

Use these only when azithromycin or doxycycline are contraindicated or not tolerated:

• Levofloxacin 500 mg orally once daily for 7 days – 88-94% efficacy (inferior to first-line) 1
• Ofloxacin 300 mg orally twice daily for 7 days – similar efficacy to first-line but more expensive with no compliance advantage 1
• Erythromycin base 500 mg orally four times daily for 7 days – less efficacious with poor compliance due to gastrointestinal side effects 1, 2, 5
• Erythromycin ethylsuccinate 800 mg orally four times daily for 7 days 1, 5

Treatment During Pregnancy

Doxycycline and all fluoroquinolones (ofloxacin, levofloxacin) are absolutely contraindicated in pregnancy. 1, 2

Preferred regimen:

• Azithromycin 1 g orally, single dose 1, 2

Alternative regimen:

• Amoxicillin 500 mg orally three times daily for 7 days 1, 2

Secondary alternatives (when azithromycin and amoxicillin cannot be used):

• Erythromycin base 500 mg orally four times daily for 7 days 1, 5
• Erythromycin base 250 mg orally four times daily for 14 days 1
• Erythromycin ethylsuccinate 800 mg orally four times daily for 7 days 1, 5
• Erythromycin ethylsuccinate 400 mg orally four times daily for 14 days 1

Never use erythromycin estolate in pregnancy—it causes drug-related hepatotoxicity. 1, 5

Mandatory follow-up: All pregnant patients must undergo test-of-cure 3-4 weeks after completing therapy (preferably by culture) because alternative regimens have lower efficacy and higher non-compliance rates 1

Lymphogranuloma Venereum (LGV)

Doxycycline is the drug of choice for LGV. 6

• Doxycycline 100 mg orally twice daily for 21 days (extended duration compared to uncomplicated infection) 6
• For pregnant/lactating women: Use erythromycin or azithromycin 6

Pediatric Dosing

For children ≥8 years weighing >45 kg:

• Azithromycin 1 g orally, single dose OR doxycycline 100 mg orally twice daily for 7 days 1, 2

For children <45 kg:

• Erythromycin base or ethylsuccinate 50 mg/kg/day orally divided into four doses for 14 days (maximum 2 g/day) 1, 5

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

• Erythromycin base or ethylsuccinate 50 mg/kg/day orally divided into four doses for 14 days – approximately 80% effective; second course may be needed 1
• Azithromycin suspension 20 mg/kg/day orally once daily for 3 days is an alternative 1
• Caution: Avoid erythromycin in neonates <1 month due to risk of infantile hypertrophic pyloric stenosis (IHPS) 5

Sexual Activity Restrictions and Partner Management

Patients must abstain from all sexual intercourse for 7 days after initiating treatment and until all sex partners have completed treatment. 1, 2

All sex partners from the previous 60 days must be evaluated, tested, and empirically treated with the same regimen—even if asymptomatic. 1, 2

• If last sexual contact was >60 days before diagnosis, treat the most recent partner 1, 2
• Do not wait for partner test results before treating—empiric treatment prevents ongoing transmission and complications 1
• Failing to treat partners leads to reinfection in up to 20% of cases 1

Coinfection Management

If gonorrhea is confirmed or prevalence is high (>5%), treat for both infections concurrently:

• Ceftriaxone 250 mg IM single dose PLUS azithromycin 1 g orally single dose 1
• Coinfection rates are 20-40% in high-prevalence populations 1

All patients diagnosed with chlamydia should be tested for gonorrhea, syphilis, and HIV at the initial visit. 1

Follow-Up and Test-of-Cure

Test-of-cure is NOT recommended for non-pregnant patients treated with recommended regimens (azithromycin or doxycycline) who are asymptomatic after treatment—cure rates exceed 97%. 1, 2

Do NOT test before 3 weeks post-treatment—nucleic acid amplification tests yield false-positives from residual dead organisms. 1

Test-of-cure IS indicated when:

• Therapeutic compliance is questionable 1, 2
• Symptoms persist after treatment 1, 2
• Reinfection is suspected 1, 2
• Patient is pregnant (mandatory) 1

Reinfection Screening (Distinct from Test-of-Cure)

All women with chlamydia must be retested approximately 3 months after treatment to screen for reinfection—regardless of whether partners were reportedly treated. 1, 2

• Reinfection rates reach up to 39% in some adolescent populations 1
• Repeat infections carry elevated risk for pelvic inflammatory disease and complications compared to initial infection 1

Men may also benefit from retesting at 3 months, though evidence is more limited. 1

Critical Pitfalls to Avoid

• Do NOT use doxycycline for <7 days—shorter courses increase treatment failure 1
• Do NOT use erythromycin estolate in pregnancy—causes hepatotoxicity 1, 5
• Do NOT use fluoroquinolones or tetracyclines in pregnancy—teratogenic risk 1, 2
• Do NOT wait for partner test results before treating—treat empirically 1
• Do NOT perform test-of-cure in asymptomatic non-pregnant patients on recommended regimens—wastes resources and may yield false-positives 1
• Do NOT assume partners were treated—directly verify or use expedited partner therapy 1
• Do NOT retreat based on symptoms alone without objective signs of urethral inflammation or laboratory evidence 1

Persistent or Recurrent Symptoms

If symptoms persist after completing treatment:

• Consider testing for Mycoplasma genitalium using NAAT on first-void urine or urethral swab—this organism causes doxycycline-resistant urethritis 1
• For confirmed M. genitalium infection: Moxifloxacin 400 mg orally once daily for 7 days is highly effective, particularly for macrolide-resistant strains 1