What is the recommended treatment for uncomplicated genital Chlamydia trachomatis infection in sexually active adults, including alternatives for pregnancy, allergy, and partner management?

Treatment of Uncomplicated Genital Chlamydia Trachomatis Infection

First-Line Treatment Recommendations

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. 1

Choosing Between First-Line Options

Azithromycin 1 g single dose is preferred when:

• Compliance is uncertain or unpredictable 1, 2
• The patient has erratic health-care-seeking behavior 1
• Directly observed therapy is desired 1
• Follow-up is unlikely 1

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

• Cost is a primary concern (significantly less expensive than azithromycin) 1, 3
• The patient has rectal chlamydia (94-100% cure vs. 76-87% with azithromycin) 1
• The patient can reliably complete a 7-day regimen 1

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

Use these alternatives only when the patient has documented allergy or severe intolerance to both azithromycin and doxycycline: 1

• Levofloxacin 500 mg orally once daily for 7 days (88-94% efficacy; lacks clinical trial validation) 1
• Ofloxacin 300 mg orally twice daily for 7 days (similar efficacy to first-line agents but more expensive) 1
• Erythromycin base 500 mg orally four times daily for 7 days (less efficacious; poor compliance due to GI side effects) 1, 4
• Erythromycin ethylsuccinate 800 mg orally four times daily for 7 days 1, 4

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Treatment During Pregnancy

Azithromycin 1 g orally as a single dose is the preferred treatment for pregnant women. 1

Alternative options for pregnancy:

• Amoxicillin 500 mg orally three times daily for 7 days 1
• Erythromycin base 500 mg orally four times daily for 7 days (if azithromycin cannot be tolerated) 1, 4
• Erythromycin base 250 mg orally four times daily for 14 days 1
• Erythromycin ethylsuccinate 800 mg orally four times daily for 7 days 1
• Erythromycin ethylsuccinate 400 mg orally four times daily for 14 days 1

Absolutely contraindicated in pregnancy:

• Doxycycline 1
• All fluoroquinolones (ofloxacin, levofloxacin) 1
• Erythromycin estolate (causes hepatotoxicity) 1, 4

Mandatory test-of-cure for pregnant patients: Perform 3-4 weeks after completing therapy, preferably by culture, because alternative regimens have lower efficacy and higher rates of non-compliance. 1

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Pediatric Dosing

For children ≥8 years weighing >45 kg:

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

For children <45 kg:

• Erythromycin base or ethylsuccinate 50 mg/kg/day orally divided into four doses daily for 14 days 1, 4

For neonates with chlamydial conjunctivitis or pneumonia (ages 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 a second course) 1, 4

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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 been treated. 1, 2

Partner Management Protocol

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

• If the last sexual contact was >60 days before diagnosis, the most recent partner must still be treated 1
• Partners should receive the same first-line regimen (azithromycin 1 g single dose or doxycycline 100 mg twice daily for 7 days) 1
• Failing to treat sex partners leads to reinfection in up to 20% of cases 1

Expedited partner therapy (EPT) may be used when partners are unable or unwilling to present for evaluation, provided they have no symptoms and no known drug allergies. 1

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Concurrent Gonorrhea Management

If gonorrhea is confirmed OR prevalence exceeds 5% in the patient population, treat for both infections concurrently: 1, 2

• Ceftriaxone 250 mg IM single dose PLUS azithromycin 1 g orally single dose 1, 2
• Coinfection rates range from 20-40% in many populations 2, 5
• In high-prevalence settings, presumptive treatment for both infections is appropriate even without testing 2

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Follow-Up and Retesting Strategy

Test-of-Cure (NOT Recommended for Most Patients)

Test-of-cure is NOT recommended for non-pregnant patients treated with recommended regimens who are asymptomatic after treatment, as cure rates exceed 97%. 1, 2

Test-of-cure should ONLY be performed when:

• Therapeutic compliance is questionable 1
• Symptoms persist after completing therapy 1
• Reinfection is suspected 1
• The patient is pregnant (mandatory) 1

Do NOT perform test-of-cure before 3 weeks post-treatment: Nucleic acid amplification tests can yield false-positive results from dead organisms that persist after successful treatment. 1

Reinfection Screening (Mandatory for All Women)

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, 5

• Reinfection rates reach up to 39% in some adolescent populations 1
• Repeat infections carry elevated risk for pelvic inflammatory disease, ectopic pregnancy, and infertility compared to initial infection 1, 6
• Men may also benefit from retesting at 3 months, though evidence is more limited 1

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Additional STI Testing at Initial Visit

All patients diagnosed with chlamydia should be tested for:

• Gonorrhea (NAAT) 1, 2
• Syphilis 1
• HIV 1

Consider HPV vaccination referral if age-appropriate. 1

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Implementation Best Practices

Dispense medications on-site when possible and directly observe the first dose to maximize compliance. 1

• This is particularly important for azithromycin single-dose therapy 1
• Ensures the patient receives at least one therapeutic dose 1

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Common Pitfalls to Avoid

• Do NOT wait for test results if compliance with return visit is uncertain in high-prevalence populations—treat presumptively 2
• Do NOT perform test-of-cure before 3 weeks post-treatment (false-positives from dead organisms) 1
• Do NOT assume partners were treated—directly verify or use expedited partner therapy 1, 2
• Do NOT use erythromycin as first-line treatment (poor compliance from GI side effects) 1
• Do NOT use fluoroquinolones in pregnancy (teratogenic risk) 1
• Do NOT retreat based on symptoms alone without documenting objective signs of urethral inflammation (≥5 WBC per high-power field) 1
• Do NOT omit the mandatory 3-month reinfection screening in women 1, 2, 5