What is the recommended therapy and follow‑up for a pregnant woman with uncomplicated urogenital Chlamydia trachomatis infection?

Chlamydia Treatment in Pregnancy

Recommended First-Line Therapy

Azithromycin 1 g orally as a single dose is the preferred treatment for pregnant women with uncomplicated urogenital Chlamydia trachomatis infection. 1, 2, 3

This recommendation represents a significant evolution from older guidelines. While earlier CDC recommendations (1993-1998) listed erythromycin base as the primary option with azithromycin as an alternative due to insufficient safety data 4, current evidence strongly supports azithromycin as first-line therapy based on superior efficacy and tolerability 1, 2, 3.

Key advantages of azithromycin in pregnancy:

• Single-dose therapy eliminates compliance issues that plague multi-day regimens 1, 2, 5
• Superior cure rates: 95.5% with azithromycin versus 78.9% with erythromycin in pregnant women 5
• Dramatically fewer severe side effects: Only 7.4% of pregnant patients on azithromycin reported side effects severe enough to warrant medication change, compared to 38.8% on erythromycin 5
• Directly observed therapy is feasible when given in clinic, ensuring treatment completion 1, 2

Alternative Regimen

Amoxicillin 500 mg orally three times daily for 7 days is the recommended alternative when azithromycin cannot be used 1, 2, 3, 6

• Amoxicillin demonstrates equivalent efficacy to azithromycin (58% vs 64% cure rates, not statistically different) in pregnancy 6
• This option is appropriate for patients with azithromycin intolerance or allergy 1, 3

Secondary Alternatives (When First Two Options Fail)

If neither azithromycin nor amoxicillin can be tolerated, use erythromycin regimens 4, 1, 3:

• Erythromycin base 500 mg orally four times daily for 7 days 4, 1, 3, 7
• Erythromycin base 250 mg orally four times daily for 14 days 4, 3
• Erythromycin ethylsuccinate 800 mg orally four times daily for 7 days 4, 1
• Erythromycin ethylsuccinate 400 mg orally four times daily for 14 days 4

Critical warning: Erythromycin estolate is absolutely contraindicated in pregnancy due to drug-related hepatotoxicity 4, 3, 8

Absolute Contraindications in Pregnancy

The following medications must never be used in pregnant women 4, 1, 2, 3, 8:

• Doxycycline
• Ofloxacin
• Levofloxacin
• All fluoroquinolones

Mandatory Follow-Up Protocol

All pregnant women require test-of-cure 3-4 weeks after treatment completion 4, 1, 3. This differs from non-pregnant patients, who do not need routine test-of-cure with recommended regimens 1, 2.

Rationale for mandatory test-of-cure in pregnancy:

• Alternative regimens (erythromycin, amoxicillin) have lower efficacy than doxycycline 4
• Gastrointestinal side effects of erythromycin frequently lead to non-compliance 4, 2
• Untreated maternal infection causes neonatal conjunctivitis (5-12 days after birth) and pneumonia (1-3 months of age) 3
• Prevalence of C. trachomatis in pregnant women exceeds 5% regardless of demographics 4, 3

Testing method: Culture is preferred for test-of-cure when available 4. If using nucleic acid amplification tests (NAATs), wait at least 3-4 weeks post-treatment to avoid false-positives from residual dead organisms 1.

Partner Management

All sexual partners from the preceding 60 days must receive empiric treatment without waiting for test results 1, 2, 3. If the last sexual contact occurred >60 days before diagnosis, treat the most recent partner 4, 1.

• Partners should receive the same treatment as non-pregnant adults: azithromycin 1 g single dose or doxycycline 100 mg twice daily for 7 days 1, 2
• Failure to treat partners results in reinfection rates up to 20% 1
• Both patient and all partners must abstain from sexual intercourse for 7 days after initiating treatment and until all partners complete therapy 4, 1, 2, 3

Screening for Co-Infections

Test all pregnant women with chlamydia for concurrent gonorrhea 3. Coinfection rates range from 20-40% in high-prevalence populations 1.

If gonorrhea is confirmed or suspected:

• Add ceftriaxone 250 mg intramuscularly as a single dose to the chlamydia regimen 1, 3
• The combination of ceftriaxone plus azithromycin treats both infections effectively 1, 3

Critical Pitfalls to Avoid

1. Do not use erythromycin estolate – it causes hepatotoxicity in pregnancy 4, 3, 8
2. Do not skip test-of-cure in pregnant patients – unlike non-pregnant adults, this is mandatory 4, 1, 3
3. Do not test before 3 weeks post-treatment – NAATs will yield false-positives 1
4. Do not assume partners were treated – directly verify or use expedited partner therapy 1
5. Do not use fluoroquinolones or tetracyclines – these are teratogenic 4, 1, 2, 3, 8

Reinfection Screening

Retest at approximately 3 months after treatment (separate from the 3-4 week test-of-cure) to detect reinfection 1, 2. This applies even when partners were reportedly treated, as reinfection rates reach 39% in some populations 1.