What is the first‑line treatment for uncomplicated urogenital Chlamydia trachomatis infection in non‑pregnant adults, and what are the recommended alternatives for doxycycline‑intolerant patients and for pregnant patients?

First-Line Treatment for Uncomplicated Urogenital Chlamydia

For non-pregnant adults with uncomplicated urogenital chlamydia, either azithromycin 1 g orally as a single dose or doxycycline 100 mg orally twice daily for 7 days are equally effective first-line options, both achieving 97-98% cure rates. 1

Choosing Between First-Line Options

Azithromycin 1 g Single Dose

• Preferred when compliance is uncertain or in populations with erratic health-care-seeking behavior (homeless individuals, adolescents, transient populations) because it enables directly observed therapy in the clinic 1, 2
• Achieves approximately 97% microbiological cure 1
• More cost-effective when follow-up is unpredictable 1
• Eliminates adherence concerns with single-dose administration 1

Doxycycline 100 mg Twice Daily for 7 Days

• Achieves approximately 98% microbiological cure 1
• Lower cost than azithromycin with extensive clinical experience 1
• Superior efficacy for rectal chlamydia (94-100% cure vs 79-87% with azithromycin; adjusted OR 0.43,95% CI 0.21-0.91, p=0.0274) 3, 1
• Requires full 7-day course—shortening the duration leads to treatment failure 1, 4

Alternative Once-Daily Doxycycline Formulation

• Doxycycline hyclate delayed-release 200 mg once daily for 7 days (Doryx) is FDA-approved and achieves equivalent 95.5% cure rates 5, 4
• Better tolerated: nausea occurs in 13% vs 21% with standard doxycycline; vomiting in 8% vs 12% 5, 4
• May improve adherence over twice-daily dosing 5

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Alternative Regimens for Doxycycline-Intolerant Patients

When patients cannot tolerate azithromycin or doxycycline, use one of these alternatives (listed in order of preference based on efficacy and tolerability):

Fluoroquinolone Options

• Ofloxacin 300 mg orally twice daily for 7 days has similar efficacy to first-line agents but offers no compliance advantage and is more expensive 1
• Levofloxacin 500 mg orally once daily for 7 days achieves 88-94% cure rates (inferior to 97-98% for first-line agents) and lacks clinical trial validation for chlamydia 1

Erythromycin Options (Less Preferred)

• Erythromycin base 500 mg orally four times daily for 7 days 1
• Erythromycin ethylsuccinate 800 mg orally four times daily for 7 days 1
• Major limitation: Gastrointestinal side effects frequently cause poor compliance, making these less desirable alternatives 1

Critical Contraindications

• All fluoroquinolones (ofloxacin, levofloxacin) are absolutely contraindicated in pregnancy 1

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Treatment During Pregnancy

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

Alternative for Pregnant Patients

• Amoxicillin 500 mg orally three times daily for 7 days is an acceptable alternative 1

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

Absolute Contraindications in Pregnancy

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

Mandatory Follow-Up in Pregnancy

• All pregnant patients must undergo test-of-cure 3-4 weeks after completing therapy, preferably by culture 1
• This requirement differs from non-pregnant adults because alternative regimens have lower efficacy and higher rates of gastrointestinal side effects leading to non-compliance 1

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Critical Management Principles

Sexual Abstinence and Partner Treatment

• Patients must abstain from all sexual intercourse for 7 days after initiating treatment and until all sex partners have completed treatment 1
• All sex partners from the preceding 60 days must be evaluated, tested, and treated empirically, regardless of symptoms 1
• Failing to treat partners leads to reinfection in up to 20% of cases 1

Concurrent Gonorrhea Testing and Treatment

• Test all patients for gonorrhea at the initial visit using NAAT 1
• If gonorrhea is confirmed or prevalence exceeds 5%, treat concurrently with ceftriaxone 250 mg IM single dose plus azithromycin 1 g orally single dose 1
• Coinfection rates are 20-40% in high-prevalence populations 1

Test-of-Cure Recommendations

• Routine test-of-cure is NOT recommended for non-pregnant patients treated with recommended regimens (azithromycin or doxycycline) because cure rates exceed 97% 1
• Testing before 3 weeks post-treatment yields false-positive results from residual nucleic acids 1
• Test-of-cure IS indicated when: therapeutic compliance is questionable, symptoms persist, or reinfection is suspected 1

Reinfection Screening

• All women should be retested approximately 3 months after treatment to detect reinfection, regardless of whether partners were reportedly treated 1
• Reinfection rates reach up to 39% in some populations and carry elevated risk for pelvic inflammatory disease 1
• Men may also benefit from retesting at 3 months, though evidence is more limited 1

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Common Pitfalls to Avoid

• Do not shorten the 7-day doxycycline course—this leads to treatment failure with cure rates falling below 95% 4
• Do not use erythromycin as first-line treatment—gastrointestinal side effects cause poor compliance 1
• Do not perform test-of-cure in asymptomatic non-pregnant patients treated with recommended regimens—this wastes resources and may yield false-positive results 1
• Do not assume partners were treated—directly verify or use expedited partner therapy 1
• Do not wait for test results before treating partners—empiric treatment prevents complications and ongoing transmission 1
• Do not use fluoroquinolones in pregnancy under any circumstances 1

Doxycycline Administration to Minimize Adverse Effects

• Instruct patients to take doxycycline with a full glass of water and remain upright for at least 30 minutes to prevent esophageal irritation 4
• Avoid co-administration with antacids, calcium, magnesium, iron, or dairy products within 2-3 hours because these agents chelate doxycycline and reduce bioavailability 4