What is the recommended first‑line therapy for uncomplicated urogenital Chlamydia trachomatis infection, including alternatives for pregnancy, drug allergy, and co‑infection with gonorrhea?

Treatment of Chlamydia

For uncomplicated urogenital 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

Choose between two equally effective regimens based on patient-specific factors:

• Azithromycin 1 g orally, single dose achieves 97% cure rates and is preferred when:

  • Compliance with multi-day regimens is uncertain 1, 2
  • Follow-up is unpredictable (e.g., homeless populations, transient patients) 1
  • Directly observed therapy is needed 1, 2
  • The patient population has erratic health-care-seeking behavior 1

• Doxycycline 100 mg orally twice daily for exactly 7 days achieves 98% cure rates and is preferred when: 1, 2, 3

  • Cost is a primary concern (significantly less expensive than azithromycin) 1, 2
  • The patient can reliably complete a 7-day course 2
  • Anorectal chlamydia is present (94-100% cure vs. 79-87% with azithromycin) 4, 1

Critical pitfall: Do not shorten the doxycycline course below 7 days—shorter durations are associated with treatment failure. 1

Treatment During Pregnancy

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

Alternative regimens if azithromycin cannot be used:

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

Absolute contraindications in pregnancy:

• Doxycycline (teratogenic risk) 1, 2
• All fluoroquinolones including ofloxacin and levofloxacin 1, 2
• Erythromycin estolate (drug-related hepatotoxicity) 1

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 rates of non-compliance due to gastrointestinal side effects. 1

Alternative Regimens (Drug Allergy or Intolerance)

Use these only when first-line options cannot be tolerated:

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

Important caveat: Erythromycin is less efficacious than azithromycin or doxycycline, and gastrointestinal side effects frequently lead to poor compliance, making it a less desirable alternative. 1, 5

Pediatric Dosing

• Children ≥8 years weighing >45 kg: Azithromycin 1 g orally single dose OR doxycycline 100 mg orally twice daily for 7 days 1, 2
• Children <45 kg: Erythromycin base or ethylsuccinate 50 mg/kg/day orally divided into four doses daily for 14 days 1, 2
• Infants 1-3 months with chlamydial pneumonia: Erythromycin base or ethylsuccinate 50 mg/kg/day orally divided into four doses daily for 14 days (approximately 80% effective; may require second course) 1

Co-Infection with Gonorrhea

If gonorrhea is confirmed or prevalence exceeds 5% in your patient population, treat both infections concurrently: 1, 2

• Ceftriaxone 250 mg IM single dose PLUS azithromycin 1 g orally single dose 6, 1

This dual therapy addresses the high coinfection rates (20-40% in high-prevalence populations) and prevents treatment failure when gonorrhea is present. 1

Sexual Abstinence and Partner Management

• Patients must abstain from all sexual intercourse for 7 days after initiating treatment and until all symptoms resolve 1, 2
• Continue abstinence until all sex partners have completed treatment 1, 2
• All sex partners from the preceding 60 days must be evaluated, tested, and empirically treated with the same regimen, regardless of symptom status 1, 2
• If the last sexual contact was >60 days before diagnosis, treat the most recent partner 1

Critical pitfall: Do not assume partners were treated—directly verify or use expedited partner therapy strategies. Failing to treat sex partners leads to reinfection in up to 20% of cases. 1

Medication Administration Best Practices

• Dispense medications on-site when possible 1, 2
• Directly observe the first dose to maximize compliance 1, 2
• Administer doxycycline with adequate fluid to reduce risk of esophageal irritation 3
• If gastric irritation occurs with doxycycline, give with food or milk (absorption not significantly affected) 3

Follow-Up and Test-of-Cure

Routine test-of-cure is NOT recommended for non-pregnant patients treated with recommended regimens because cure rates exceed 97% and treatment failure rates are extremely low (0-3% in males, 0-8% in females). 1, 2, 5

Perform test-of-cure only when:

• Therapeutic compliance is questionable 1, 2
• Symptoms persist after treatment 1, 2
• Reinfection is suspected 1, 2
• The patient is pregnant (mandatory 3-4 weeks post-treatment) 1

Timing caveat: Wait at least 3 weeks after treatment before testing—nucleic acid amplification tests performed earlier can yield false-positive results from dead organisms that persist after successful treatment. 1, 2

Reinfection Screening (Distinct from Test-of-Cure)

All women with chlamydia should be retested approximately 3 months after treatment, regardless of whether partners were reportedly treated. 1, 2, 5

Rationale:

• Reinfection rates reach up to 39% in some adolescent populations 1, 2
• Repeat infections carry elevated risk for pelvic inflammatory disease and other complications compared to initial infection 1, 2

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

Management of Treatment Failure

If symptoms persist after completing recommended therapy:

1. Do not retreat based on symptoms alone—require objective evidence of urethral inflammation (≥5 WBC per high-power field) before considering additional therapy 1

2. If failure is due to non-adherence or re-exposure to untreated partner: Retreat with the same first-line regimen 1

3. If true treatment failure after azithromycin: Switch to doxycycline 100 mg orally twice daily for 7 days 2

4. Consider Mycoplasma genitalium if symptoms persist after completing doxycycline—test using NAAT on first-void urine or urethral swab; treat confirmed M. genitalium with moxifloxacin 400 mg orally once daily for 7 days 1

Additional STI Testing at Initial Visit

All patients diagnosed with chlamydia should be tested for:

• Gonorrhea 1
• Syphilis 1
• HIV 1