What is the recommended treatment for uncomplicated genital Chlamydia trachomatis infection in women, including first‑line therapy, alternatives for doxycycline intolerance or pregnancy, partner management, and test‑of‑cure recommendations?

Treatment of Uncomplicated Genital Chlamydia in Women

For uncomplicated genital Chlamydia trachomatis infection in non-pregnant women, 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 orally as a single dose when:

• Compliance with a 7-day regimen is uncertain 1, 2
• The patient has erratic health-care-seeking behavior 1
• You can directly observe therapy in the clinic, eliminating risk of incomplete treatment 2
• The patient is unlikely to return for follow-up 1

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

• Cost is the primary concern (doxycycline is significantly less expensive) 1, 2
• The patient has reliable follow-through with multi-day regimens 1
• The patient has rectal chlamydia (doxycycline shows superior efficacy: 94% cure vs. 85% with azithromycin) 1

Both regimens have similar mild gastrointestinal side effects (17-20% of patients), though the once-daily delayed-release doxycycline formulation (200 mg daily for 7 days) reduces nausea and vomiting if standard doxycycline is poorly tolerated 1, 3

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

Use these alternatives only when the patient cannot tolerate azithromycin or doxycycline:

• Levofloxacin 500 mg orally once daily for 7 days (88-94% efficacy, but lacks clinical trial validation) 1, 2
• Ofloxacin 300 mg orally twice daily for 7 days (similar efficacy to first-line agents but more expensive with no compliance advantage) 1, 2
• Erythromycin base 500 mg orally four times daily for 7 days (less efficacious, poor compliance due to gastrointestinal side effects) 1, 4
• Erythromycin ethylsuccinate 800 mg orally four times daily for 7 days 1, 4

Critical caveat: Erythromycin should not be used as first-line treatment due to poor compliance from gastrointestinal side effects 1, 2

Treatment During Pregnancy

Azithromycin 1 g orally as a single dose is the preferred treatment during pregnancy. 1, 4

Alternative option for pregnant patients:

• Amoxicillin 500 mg orally three times daily for 7 days 1, 4

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

• 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

Absolutely contraindicated in pregnancy:

• Doxycycline (teratogenic) 1, 4
• All fluoroquinolones including ofloxacin and levofloxacin (teratogenic) 1, 4
• Erythromycin estolate (drug-related hepatotoxicity) 1

Mandatory follow-up for pregnant patients: 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 1

Sexual Activity Restrictions (Critical for All Patients)

Patients must abstain from all sexual intercourse for 7 days after initiating treatment, regardless of which regimen is used. 1, 2, 4

Sexual activity must remain restricted until all sex partners have been treated to prevent reinfection. 1, 2

Failing to treat sex partners leads to reinfection in up to 20% of cases 2

Partner Management Protocol

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

If the last sexual contact was >60 days before diagnosis, the most recent partner must still be treated. 1, 2

Treat partners empirically without waiting for their test results—delaying treatment increases risk of complications and ongoing transmission 1

Partners should receive the same first-line regimen (azithromycin 1 g single dose or doxycycline 100 mg twice daily for 7 days) 1

Test-of-Cure Recommendations

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

Perform test-of-cure only in these specific situations:

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

Critical timing: Do NOT perform test-of-cure before 3 weeks post-treatment, as nucleic acid amplification tests can yield false-positive results from dead organisms that persist after successful treatment 1, 2

Mandatory 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, 4

This is mandatory because:

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

Concurrent Gonorrhea Management

If gonorrhea is confirmed or prevalence is high (>5%) in the patient population, treat for both infections concurrently with ceftriaxone 250 mg IM single dose PLUS azithromycin 1 g orally single dose. 1, 2

Coinfection rates range from 20-40% in many populations, making presumptive dual therapy cost-effective in high-prevalence settings 2, 4

Additional Testing at Initial Visit

Test for gonorrhea, syphilis, and HIV at the time of chlamydia diagnosis 1

Consider HPV vaccination referral if age-appropriate 1, 2

Implementation Best Practices

Dispense medications on-site when possible and directly observe the first dose to maximize compliance. 1, 4

This is particularly important for azithromycin single-dose therapy, which allows for directly observed treatment 1, 2

Common Pitfalls to Avoid

• Do NOT wait for test results if compliance with return visit is uncertain in high-prevalence populations—treat presumptively 1, 2
• Do NOT assume partners were treated—directly verify or use expedited partner therapy strategies 1, 2
• Do NOT perform test-of-cure before 3 weeks post-treatment (false-positives from residual DNA) 1, 2
• Do NOT use erythromycin as first-line treatment due to poor compliance from gastrointestinal side effects 1, 2
• Do NOT omit the mandatory 3-month reinfection screening in women 1, 2
• Do NOT use doxycycline, fluoroquinolones, or erythromycin estolate in pregnancy 1, 4