What are the recommended first‑line regimens for uncomplicated urogenital Chlamydia trachomatis and Neisseria gonorrhoeae infection in adults, including pregnant patients and those weighing ≥150 kg?

First-Line Treatment for Chlamydia and Gonorrhea

Chlamydia trachomatis: First-Line Regimens

For uncomplicated urogenital 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, 2, 3

Choosing Between First-Line Options

• Azithromycin 1 g single dose is preferred when:

  • Compliance is uncertain or follow-up is unpredictable 1, 2
  • Directly observed therapy is needed 1, 2
  • Patient has erratic health-care-seeking behavior 2

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

  • Cost is a primary concern (significantly less expensive than azithromycin) 1, 2, 3
  • Patient can reliably complete 7-day regimen 2, 3

Alternative Regimens for Chlamydia

When first-line options cannot be used, alternatives include 4, 1, 2, 3:

• Erythromycin base 500 mg orally four times daily for 7 days
• Levofloxacin 500 mg orally once daily for 7 days (inferior evidence, 88-94% efficacy vs 97-98% for first-line agents) 2
• Ofloxacin 300 mg orally twice daily for 7 days 4, 2

Critical caveat: Erythromycin causes frequent gastrointestinal side effects leading to poor compliance, making it less desirable 2, 3

Chlamydia Treatment During Pregnancy

Azithromycin 1 g orally as a single dose is the preferred treatment during pregnancy. 1, 2

• Alternative: Amoxicillin 500 mg orally three times daily for 7 days 1, 2, 5
• Absolutely contraindicated in pregnancy: Doxycycline, ofloxacin, levofloxacin, and all fluoroquinolones 2, 3
• Erythromycin estolate is contraindicated due to drug-related hepatotoxicity 4, 2

Pregnant women require test-of-cure 3-4 weeks after treatment completion due to use of alternative regimens with lower efficacy 2

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Neisseria gonorrhoeae: First-Line Regimens

For uncomplicated urogenital gonorrhea, current CDC guidelines recommend ceftriaxone 500 mg IM as a single dose (or 1 g IM if patient weighs ≥150 kg). While the provided evidence references older regimens 6, contemporary practice has shifted away from oral cephalosporins due to resistance concerns.

Critical Coinfection Management

When treating gonorrhea OR when gonorrhea prevalence is high (>5%) in your patient population, ALWAYS treat for both chlamydia and gonorrhea concurrently with ceftriaxone 250 mg IM single dose PLUS azithromycin 1 g orally single dose, as coinfection rates reach 20-40%. 1, 2

• All patients with confirmed gonorrhea should receive presumptive chlamydia treatment 2
• All chlamydia patients should be tested for gonorrhea, syphilis, and HIV at initial visit 1

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Implementation Best Practices

Medication Administration

• Dispense medication on-site when possible and directly observe the first dose to maximize compliance 1, 2, 3
• This is particularly critical for azithromycin single-dose therapy 1

Sexual Activity Restrictions

• Patients must abstain from ALL sexual intercourse for 7 days after initiating treatment AND until all sex partners are treated 1, 2
• This applies regardless of which regimen is used 2

Partner Management

• All sex partners from the previous 60 days must be evaluated, tested, and empirically treated—even if asymptomatic 1, 2
• Treat partners immediately without waiting for their test results, as delaying treatment increases transmission risk and complications 2
• If last sexual contact was >60 days before diagnosis, still treat the most recent partner 2, 3

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Follow-Up and Reinfection Screening

Test-of-Cure

• Test-of-cure is NOT recommended for non-pregnant patients treated with recommended regimens who are asymptomatic, as cure rates exceed 97% 1, 2, 3
• Testing before 3 weeks post-treatment yields false-positives from dead organisms 2

Mandatory Reinfection Screening

• ALL women with chlamydia must be retested at 3 months post-treatment, as reinfection rates reach 39% in some populations and carry elevated risk for pelvic inflammatory disease 1, 2, 3
• This is distinct from test-of-cure and should be performed regardless of whether partners were reportedly treated 2
• Men may also benefit from 3-month retesting, though evidence is more limited 2

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Special Populations

Pediatric Dosing for Chlamydia

• Children ≥8 years weighing >45 kg: Azithromycin 1 g orally single dose OR doxycycline 100 mg orally twice daily for 7 days 2, 3
• Children <45 kg: Erythromycin base or ethylsuccinate 50 mg/kg/day orally divided into four doses daily for 14 days 2
• Infants with chlamydial pneumonia (1-3 months): Erythromycin base or ethylsuccinate 50 mg/kg/day divided into four doses for 14 days (80% effective; may need second course) 2

Patients Weighing ≥150 kg

• For gonorrhea treatment in patients ≥150 kg, increase ceftriaxone dose to 1 g IM single dose (based on contemporary CDC guidance, though not explicitly detailed in provided older evidence)
• Chlamydia dosing remains standard regardless of weight 1, 2, 3

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Critical Pitfalls to Avoid

1. Never wait for test results before treating sex partners—empiric treatment prevents ongoing transmission 2
2. Never perform test-of-cure in asymptomatic patients on recommended regimens—this wastes resources and may yield false-positives 2
3. Never assume partners were treated—directly verify or use expedited partner therapy 2
4. Never treat chlamydia alone when gonorrhea is confirmed or highly prevalent—always treat both concurrently 1, 2
5. Never use non-culture tests (EIA, DFA) in children—risk of false-positives from cross-reaction with other organisms 2
6. Never forget the mandatory 3-month reinfection screening for women—this is not optional 1, 2