Treatment of Uncomplicated Urogenital Chlamydia Trachomatis Infection

First-Line Therapy

Either azithromycin 1 g orally as a single dose or doxycycline 100 mg orally twice daily for 7 days should be used as first-line treatment, with both achieving 97–98% cure rates. 1, 2

Choosing Between First-Line Options

Azithromycin 1 g single dose is preferred when:
- Compliance with a 7-day regimen is uncertain 1, 2
- The patient has erratic health-care-seeking behavior (e.g., homelessness, transient populations) 1, 2
- Directly observed therapy is needed to ensure treatment completion 1, 2
- Follow-up is unpredictable 1
Doxycycline 100 mg twice daily for 7 days is preferred when:
- Cost is a primary concern (doxycycline is less expensive) 1
- The patient has rectal chlamydia, where doxycycline demonstrates superior efficacy (94–100% cure vs. 79–87% with azithromycin) 1, 3
- The patient can reliably complete a 7-day course 1
Alternative once-daily doxycycline formulation: Doxycycline hyclate delayed-release 200 mg once daily for 7 days is FDA-approved and achieves equivalent 95% cure rates with reduced gastrointestinal side effects (13% nausea vs. 21% with standard dosing) 4, 3

Critical Implementation Steps

Dispense medication on-site and directly observe the first dose (especially with azithromycin) to maximize compliance 1, 2
Patients must abstain from all sexual intercourse for 7 days after initiating treatment, regardless of which regimen is used 1, 2
For azithromycin, the 7-day abstinence period applies even though it's a single dose, because tissue concentrations build over time 2

Alternative Regimens (Doxycycline Intolerance or Allergy)

When first-line agents cannot be used, the following alternatives are recommended in descending order of preference:

Erythromycin base 500 mg orally four times daily for 7 days 1
Erythromycin ethylsuccinate 800 mg orally four times daily for 7 days 1
Ofloxacin 300 mg orally twice daily for 7 days 1
Levofloxacin 500 mg orally once daily for 7 days (cure rates 88–94% vs. 97–98% for first-line agents; lacks clinical trial validation) 1

Important Caveats

Erythromycin has lower efficacy than azithromycin or doxycycline and causes gastrointestinal side effects that lead to poor compliance 1, 2
Fluoroquinolones (ofloxacin, levofloxacin) offer no compliance advantage over doxycycline (both require 7 days) and are more expensive 1
Levofloxacin efficacy is extrapolated from ofloxacin data, not proven in clinical trials 1

Treatment During Pregnancy

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

Alternative Regimens for Pregnancy

If azithromycin cannot be used:

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 risk) 1, 3, 2
All fluoroquinolones (ofloxacin, levofloxacin) 1
Erythromycin estolate (drug-related hepatotoxicity) 1

Mandatory Follow-Up in Pregnancy

All pregnant patients require test-of-cure 3–4 weeks after completing therapy (unlike non-pregnant patients) 1
Rationale: Alternative regimens have lower efficacy and higher rates of non-compliance due to gastrointestinal side effects 1
Culture is the preferred test-of-cure method when available; if using NAAT, wait ≥3 weeks to avoid false-positives from residual DNA 1

Partner Management

All sex partners from the preceding 60 days must be evaluated, tested, and empirically treated, regardless of symptoms or test results. 1, 2

If the last sexual contact was >60 days before diagnosis, treat the most recent partner anyway 1
Partners should receive the same treatment regimen as the index patient 1
Do not wait for partner test results before treating; empiric treatment is mandatory because sex partners have substantially increased risk of infection 1
For partners unable or unwilling to present for evaluation, treatment without physical examination is acceptable if they are asymptomatic and have no drug allergies 1
Both patient and all partners must abstain from intercourse for 7 days after initiating therapy and until all partners have completed treatment 1, 2

Counseling and Concurrent STI Testing

Mandatory Testing at Initial Visit

Test for gonorrhea, syphilis, and HIV when chlamydia is diagnosed 1
If gonorrhea is confirmed or prevalence exceeds 5% in the population, treat presumptively for both infections with ceftriaxone 250 mg IM single dose plus azithromycin 1 g orally single dose 1, 2

Preventive Counseling

Refer for HPV vaccination 1
Offer smoking cessation counseling 1
Offer influenza vaccine 1
Document patient refusal if declined 1

Retesting Schedule

Test-of-Cure (NOT Recommended for Most Patients)

Routine test-of-cure is NOT recommended for non-pregnant patients treated with recommended regimens (azithromycin or doxycycline) because cure rates exceed 97%. 1, 3, 2

Test-of-cure should only be performed when:

Therapeutic compliance is questionable 1
Symptoms persist after completing therapy 1
Reinfection is suspected 1
The patient is pregnant (mandatory test-of-cure 3–4 weeks post-treatment) 1

Critical timing: Testing before 3 weeks post-treatment is unreliable because NAAT can yield false-positives from dead organism DNA 1, 3, 2

Reinfection Screening (Mandatory for All Women)

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

Reinfection occurs in up to 39% of adolescent populations 1
Repeat infections carry elevated risk for pelvic inflammatory disease and complications compared to initial infection 1
Men may also benefit from retesting at 3 months, though evidence is more limited 1
Retesting at 3 months is distinct from test-of-cure and should be performed even if the patient is asymptomatic 1, 2

Common Pitfalls to Avoid

Do not shorten the 7-day doxycycline course; this leads to treatment failure with cure rates falling below 95% 1, 3
Do not wait for test results if compliance with return visits is uncertain in high-prevalence populations—treat presumptively 1, 2
Do not perform routine test-of-cure in asymptomatic, non-pregnant patients; this wastes resources and may yield false-positives 1, 3
Do not assume partners were treated—directly verify or use expedited partner therapy strategies 1
Do not retreat based on symptoms alone without documenting objective signs of urethral inflammation (≥5 WBC per high-power field) 1
Do not use erythromycin as first-line therapy; it has lower efficacy and poor compliance due to gastrointestinal side effects 1, 2
Do not use fluoroquinolones or doxycycline in pregnancy due to teratogenic risk 1, 3

What is the recommended first‑line therapy, alternative regimens for pregnancy or doxycycline intolerance, partner management, counseling, and retesting schedule for a non‑pregnant adult or adolescent with confirmed or suspected uncomplicated urogenital Chlamydia trachomatis infection?

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