What is the recommended treatment regimen for uncomplicated genital Chlamydia trachomatis infection in sexually active adults and adolescents, including options for pregnancy, macrolide allergy, partner treatment, and follow‑up?

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

First-Line Treatment Regimens

Azithromycin 1 g orally, single dose:

• Achieves approximately 97% microbiologic cure rate 1, 2
• Preferred when compliance is uncertain because it allows directly observed therapy in the clinic 1
• Better option for populations with erratic health-care-seeking behavior or unpredictable follow-up 3, 1
• Lower gastrointestinal side effects than previously reported (17-19% mild-to-moderate GI symptoms) 4, 5

Doxycycline 100 mg orally twice daily for exactly 7 days:

• Achieves approximately 98% microbiologic cure rate 1, 2
• Lower cost than azithromycin with extensive clinical experience 1, 2
• Superior efficacy for rectal chlamydia (94% cure vs. 85% with azithromycin; adjusted OR 0.43,95% CI 0.21-0.91, p=0.0274) 1
• FDA-approved dosing: 200 mg on day 1 (100 mg every 12 hours), then 100 mg daily maintenance dose 6
• Alternative once-daily formulation: doxycycline hyclate delayed-release 200 mg once daily for 7 days achieves equivalent 95.5% cure with reduced nausea (13% vs. 21%) and vomiting (8% vs. 12%) 1

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

Use these only when azithromycin and doxycycline are contraindicated or not tolerated 1:

• 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
• Ofloxacin 300 mg orally twice daily for 7 days 3, 1
• Levofloxacin 500 mg orally once daily for 7 days (cure rates 88-94%, inferior to first-line agents at 97-98%) 1

Important caveat: Erythromycin has poor compliance due to gastrointestinal side effects and is less efficacious than azithromycin or doxycycline 1. Fluoroquinolones offer no compliance benefit over doxycycline (both require 7 days) and are more expensive without superior efficacy 1.

Treatment During Pregnancy

Azithromycin 1 g orally, single dose is the preferred treatment in pregnancy. 1, 2

Alternative options for pregnant patients:

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

Absolute contraindications in pregnancy:

• Doxycycline (teratogenic) 1, 2
• Ofloxacin, levofloxacin, and all fluoroquinolones (teratogenic) 1
• Erythromycin estolate (drug-related hepatotoxicity) 1

Mandatory follow-up: All pregnant women 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 GI side effects 1.

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 for 14 days 1

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; may require second course) 1
• Alternative: Azithromycin suspension 20 mg/kg/day orally once daily for 3 days 1

Critical pitfall: Do not use non-culture tests (EIA, DFA) in children due to false-positive results from cross-reaction with other organisms 1.

Sexual Abstinence and Partner Management

Patients must abstain from all sexual intercourse for 7 days after initiating treatment (regardless of single-dose or 7-day regimen) and until all sex partners have completed treatment 3, 1.

All sex partners from the preceding 60 days must be:

• Evaluated
• Tested
• Treated empirically with the same regimen, even if asymptomatic 1, 2

If last sexual contact was >60 days before diagnosis, treat the most recent partner. 1

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

Concurrent Gonorrhea Testing and Treatment

Test all patients for gonorrhea (NAAT) at the initial visit. 1

If gonorrhea is confirmed OR prevalence in the population exceeds 5%, treat concurrently with:

• Ceftriaxone 250 mg IM single dose PLUS azithromycin 1 g orally single dose 1, 2

Coinfection with gonorrhea occurs in 20-40% of patients with chlamydia 2. Treating chlamydia alone when gonorrhea is present leads to treatment failure 1.

Follow-Up and Test-of-Cure

Routine test-of-cure is NOT recommended for non-pregnant patients treated with azithromycin or doxycycline who are asymptomatic, because cure rates exceed 97% 1, 2.

Test-of-cure IS indicated when:

• Therapeutic compliance is questionable
• Symptoms persist after completing therapy
• Reinfection is suspected 1

Timing: Test-of-cure should be performed 3-4 weeks after treatment completion. Testing before 3 weeks is unreliable because nucleic acid amplification tests yield false-positive results from dead organisms 1.

Reinfection Screening (Distinct from Test-of-Cure)

All women with chlamydia should 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, and repeat infections carry elevated risk for pelvic inflammatory disease and other complications compared to initial infection 1.

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

Additional STI Testing

At the initial visit, test all patients diagnosed with chlamydia for:

• Gonorrhea (NAAT)
• Syphilis
• HIV 1

Medication Dispensing Best Practices

Medications should be dispensed on-site when possible, with the first dose directly observed to maximize compliance 1, 7. This is particularly important for azithromycin single-dose therapy 1.

Management of Persistent or Recurrent Symptoms

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

If treatment failure is due to non-adherence or re-exposure to an untreated partner, retreat with the same first-line regimen. 1

If symptoms persist after documented compliance and partner treatment, consider testing for Mycoplasma genitalium using NAAT on first-void urine or urethral swab, as this organism causes doxycycline-resistant urethritis 1. For confirmed M. genitalium infection, moxifloxacin 400 mg orally once daily for 7 days is highly effective 1.

Special Populations

HIV-infected patients: Receive the same treatment regimens as HIV-negative patients 3, 2.

Patients with IUD in place: Treat with standard first-line regimens (azithromycin 1 g single dose or doxycycline 100 mg twice daily for 7 days); IUD removal is not required for uncomplicated cervical infection 7.

Common Clinical Pitfalls to Avoid

• Do not wait for test results if compliance with return visit is uncertain in high-prevalence populations—treat presumptively 1
• Do not perform test-of-cure in asymptomatic patients treated with recommended regimens—this wastes resources and may yield false-positive results 1
• Do not use erythromycin as first-line treatment—poor compliance from GI side effects makes it inferior 1
• Do not use fluoroquinolones in pregnancy—they are absolutely contraindicated 1
• Do not use doxycycline in pregnancy—it is teratogenic 1, 2
• Do not omit the mandatory test-of-cure in pregnant patients—alternative regimens have lower efficacy 1