What are the recommended diagnostic tests and first‑line treatment regimens for uncomplicated genital Chlamydia trachomatis infection in sexually active adults, including differences for pregnant patients and partner management?

Chlamydia Trachomatis: Diagnosis and Treatment

Diagnostic Testing

Use nucleic acid amplification tests (NAATs) for all suspected chlamydia cases—they are the gold standard for diagnosis. 1

• NAATs can be performed on first-void urine in men, endocervical or vaginal swabs in women, and rectal or pharyngeal swabs when indicated 1
• Self-collected vaginal swabs perform equivalently to clinician-collected specimens and improve screening uptake 1
• Culture is reserved for test-of-cure in pregnant women (when available) and medicolegal cases in children 1, 2
• Non-culture tests (EIA, DFA) should never be used in children due to false-positives from cross-reactivity with other organisms 2

First-Line Treatment for Non-Pregnant Adults

Treat immediately 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. 2

Azithromycin advantages:

• Single-dose directly observed therapy eliminates compliance concerns 2
• Preferred when follow-up is unpredictable or in populations with erratic healthcare-seeking behavior 2
• Better tolerated with fewer gastrointestinal side effects than erythromycin 2

Doxycycline advantages:

• Lower cost than azithromycin 2
• Superior efficacy for rectal chlamydia (94-100% vs. 79-87% with azithromycin) 2
• Extensive safety data over decades of use 2

A delayed-release doxycycline formulation (200 mg once daily for 7 days) is equally effective and causes less nausea (13% vs. 21%) and vomiting (8% vs. 12%) compared to standard dosing. 2

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

Use these only when azithromycin and doxycycline are contraindicated or not tolerated: 2

• Erythromycin base 500 mg orally four times daily for 7 days
• Erythromycin ethylsuccinate 800 mg orally four times daily for 7 days
• Ofloxacin 300 mg orally twice daily for 7 days
• Levofloxacin 500 mg orally once daily for 7 days (88-94% efficacy—inferior to first-line agents)

Erythromycin causes significant gastrointestinal side effects leading to poor compliance and should be avoided when possible. 2

Treatment During Pregnancy

Azithromycin 1 g orally as a single dose is the preferred treatment in pregnancy. 2, 3

• Alternative: Amoxicillin 500 mg orally three times daily for 7 days 2, 3
• Doxycycline, ofloxacin, levofloxacin, and all fluoroquinolones are absolutely contraindicated in pregnancy due to teratogenic risk. 2, 3
• Erythromycin estolate is contraindicated in pregnancy due to drug-related hepatotoxicity. 2, 3

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

• Erythromycin base 500 mg orally four times daily for 7 days 2, 3
• Erythromycin base 250 mg orally four times daily for 14 days 2, 3
• Erythromycin ethylsuccinate 800 mg orally four times daily for 7 days 2, 3
• Erythromycin ethylsuccinate 400 mg orally four times daily for 14 days 2, 3

All pregnant women MUST undergo test-of-cure 3-4 weeks after completing therapy, preferably by culture, because alternative regimens have lower efficacy and compliance issues. 2, 3

Pediatric Dosing

Children ≥8 years weighing >45 kg:

• Azithromycin 1 g orally as a single dose OR doxycycline 100 mg orally twice daily for 7 days 2

Children <45 kg:

• Erythromycin base or ethylsuccinate 50 mg/kg/day orally divided into four doses for 14 days 2

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; second course may be needed) 1, 2
• Alternative: Azithromycin suspension 20 mg/kg/day orally once daily for 3 days 2

Topical antibiotic therapy alone is inadequate for neonatal chlamydial conjunctivitis and is unnecessary when systemic treatment is given. 1

Sexual Activity Restrictions

Patients must abstain from ALL sexual intercourse for 7 days after initiating treatment AND until all sex partners have completed treatment. 2, 3, 4

Partner Management

All sex partners from the preceding 60 days must be evaluated, tested, and treated empirically with the same regimen—even if asymptomatic. 2, 3

• If the last sexual contact was >60 days before diagnosis, treat the most recent partner 2, 3
• Failing to treat partners leads to reinfection in up to 20% of cases 2
• Expedited partner therapy (providing medication directly to the index patient for their partner) should be used where legally permitted 3
• Medications should be dispensed on-site when possible, with the first dose directly observed to maximize compliance 2, 4

Concurrent Gonorrhea Testing and Treatment

Test all patients for gonorrhea, syphilis, and HIV at the initial visit. 2

If gonorrhea is confirmed OR prevalence exceeds 5% in your population, treat concurrently with ceftriaxone 250 mg IM single dose PLUS azithromycin 1 g orally single dose. 1, 2

• Coinfection rates are 20-40% in high-prevalence populations 2
• Treating chlamydia alone when gonorrhea is present leads to treatment failure 2

Test-of-Cure Recommendations

Routine test-of-cure is NOT recommended for non-pregnant patients treated with azithromycin or doxycycline because cure rates exceed 97%. 2, 4

Test-of-cure IS indicated when:

• Patient is pregnant (mandatory 3-4 weeks post-treatment) 2, 3
• Therapeutic compliance is questionable 2
• Symptoms persist after completing treatment 2
• Reinfection is suspected 2

Do NOT test before 3 weeks post-treatment—NAATs can yield false-positives from residual dead organisms. 2

Reinfection Screening

All women with chlamydia MUST be retested approximately 3 months after treatment to screen for reinfection, regardless of whether partners were reportedly treated. 2, 4

• Reinfection occurs in up to 39% of adolescent populations 2
• Repeat infections carry elevated risk for pelvic inflammatory disease, ectopic pregnancy, and infertility compared to initial infection 2, 5, 6
• Men may also benefit from retesting at 3 months, though evidence is more limited 2

Management of Persistent Urethritis After Treatment

Do NOT retreat based on symptoms alone—require objective evidence of urethral inflammation (≥5 WBC per high-power field). 2

If symptoms persist after completing recommended therapy:

1. Consider testing for Mycoplasma genitalium using NAAT on first-void urine or urethral swab 2, 7
2. For confirmed M. genitalium infection, use moxifloxacin 400 mg orally once daily for 7 days (highly effective for macrolide-resistant strains) 2
3. If treatment failure is due to non-adherence or re-exposure to an untreated partner, retreat with the same first-line regimen 2

Special Considerations for IUD Placement

Patients with an IUD in place and positive chlamydia test should receive standard treatment (azithromycin 1 g single dose OR doxycycline 100 mg twice daily for 7 days) without IUD removal. 4

• IUD removal is not necessary for uncomplicated chlamydial cervicitis 4
• Ensure partner treatment to prevent reinfection 4

Critical Pitfalls to Avoid

• Do NOT wait for test results before treating in high-prevalence populations when compliance with return visits is uncertain—treat presumptively 2
• Do NOT use erythromycin estolate in pregnancy (hepatotoxicity risk) 2, 3
• Do NOT omit test-of-cure in pregnant patients (mandatory) 2, 3
• Do NOT assume partners were treated—directly verify or use expedited partner therapy 2
• Do NOT perform routine test-of-cure in asymptomatic non-pregnant patients treated with recommended regimens (wastes resources and may yield false-positives) 2
• Do NOT use non-culture tests (EIA, DFA) in children (false-positives from cross-reactivity) 2