What is the recommended first‑line therapy for uncomplicated genital Chlamydia trachomatis infection in adults, including considerations for pregnancy and drug allergies?

Treatment for Chlamydia

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

Choose azithromycin 1 g single oral dose when:

• Compliance with a 7-day regimen is uncertain or unpredictable 1, 2
• The patient has erratic health-care-seeking behavior (e.g., homelessness, unstable housing) 1
• You can administer directly observed therapy in the clinic, eliminating risk of incomplete treatment 1, 3
• Follow-up is unpredictable 1

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

• Cost is the primary concern—doxycycline is significantly less expensive than azithromycin 1, 2
• The patient has rectal chlamydia—doxycycline shows superior efficacy (94-100% cure) compared to azithromycin (76-87% cure) 1
• The patient can reliably complete a 7-day course 2

Both regimens have similar rates of mild-to-moderate gastrointestinal side effects (17-20%) 1, 4. The CDC recommends dispensing medication on-site when possible and directly observing the first dose to maximize compliance. 1

Treatment During Pregnancy

Azithromycin 1 g orally as a single dose is the preferred treatment during pregnancy. 1, 2 Doxycycline and all fluoroquinolones (ofloxacin, levofloxacin) are absolutely contraindicated due to teratogenic risk. 1, 5

Alternative regimens for pregnant patients when 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, 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

Critical: Erythromycin estolate is contraindicated in pregnancy due to drug-related hepatotoxicity. 1 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 gastrointestinal side effects leading to non-compliance. 1

Alternative Regimens for Drug Allergies

When azithromycin and doxycycline cannot be used (documented allergy or severe intolerance), use one of these 7-day regimens:

• Erythromycin base 500 mg orally four times daily 1, 5
• Erythromycin ethylsuccinate 800 mg orally four times daily 1, 5
• Ofloxacin 300 mg orally twice daily 1
• Levofloxacin 500 mg orally once daily 1

Important caveats: Levofloxacin has inferior efficacy (88-94% cure rate vs. 97-98% for first-line agents) and lacks clinical trial validation for chlamydia—it should be reserved only when first-line agents cannot be used. 1 Erythromycin is less efficacious than azithromycin or doxycycline, and gastrointestinal side effects frequently cause poor compliance. 1, 2

Mandatory Sexual Activity Restrictions & Partner Management

Patients must abstain from all sexual intercourse for 7 days after initiating treatment AND until all sex partners have completed treatment. 1, 3 This applies regardless of which regimen is used. 3

All sex partners from the preceding 60 days must be evaluated, tested, and empirically treated with the same chlamydia-effective regimen, even if asymptomatic. 1, 3 If the last sexual contact was >60 days before diagnosis, the most recent partner must still be treated. 1, 3 Failing to treat sex partners leads to reinfection in up to 20% of cases. 1, 3

Concurrent Gonorrhea Management

If gonorrhea is confirmed OR prevalence exceeds 5% in your patient population, treat for both infections concurrently with ceftriaxone 250 mg IM single dose PLUS azithromycin 1 g orally single dose. 1, 3 Coinfection rates range from 20-40% in many populations. 3 All patients diagnosed with chlamydia should be tested for gonorrhea, syphilis, and HIV at the initial visit. 1

Follow-Up & Retesting Strategy

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, 3 Test-of-cure should only be performed when therapeutic compliance is questionable, symptoms persist after completing therapy, or reinfection is suspected. 1, 2

All women with chlamydia must be retested approximately 3 months after treatment to screen for reinfection, regardless of whether partners were reportedly treated. 1, 3 Reinfection rates reach up to 39% in some adolescent populations, and repeat infections carry elevated risk for pelvic inflammatory disease and other complications compared to initial infection. 1, 3

Do NOT perform test-of-cure before 3 weeks post-treatment—nucleic acid amplification tests can yield false-positive results from residual DNA of dead organisms. 1

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, 6

For children <45 kg:

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

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

• Erythromycin base or ethylsuccinate 50 mg/kg/day orally divided into four doses for 14 days (approximately 80% effective; a second course may be needed) 1, 5

Critical Pitfalls to Avoid

• Do NOT wait for test results if compliance with return visit is uncertain in high-prevalence populations—treat presumptively. 3
• Do NOT assume partners were treated—directly verify or use expedited partner therapy strategies. 1, 3
• Do NOT use erythromycin as first-line treatment due to poor compliance from gastrointestinal side effects. 1, 2
• Do NOT use non-culture tests (EIA, DFA) in children due to false-positive results from cross-reaction with other organisms. 1
• Do NOT retreat based on symptoms alone without documenting objective signs of urethral inflammation (≥5 WBC per high-power field) or laboratory evidence of infection. 1