Doxycycline is the Preferred Treatment for Chlamydia
Doxycycline 100 mg orally twice daily for 7 days is the recommended first-line treatment for uncomplicated chlamydial infection, with azithromycin 1 g orally as a single dose as an equally effective alternative. 1, 2 Both regimens achieve microbial cure rates of approximately 97-98%. 1, 2
Critical Point: Ceftriaxone (Rocephin) Has NO Activity Against Chlamydia
Ceftriaxone is NOT a treatment option for chlamydia. 3 The FDA drug label explicitly states: "Ceftriaxone for Injection, USP like other cephalosporins, has no activity against Chlamydia trachomatis." 3 Ceftriaxone is used to treat gonorrhea, and when treating gonorrhea, appropriate antichlamydial coverage (doxycycline or azithromycin) must be added if chlamydia has not been excluded. 3, 4
First-Line Treatment Selection
Doxycycline Advantages:
- Lower cost compared to azithromycin 1, 2
- Extensive clinical experience with proven safety profile 5
- 98% microbial cure rate 2
- Superior efficacy for rectal chlamydia (96.9% cure vs 76.4% with azithromycin) 6, 7
Azithromycin Advantages:
- Single-dose therapy eliminates compliance concerns 1, 2
- Directly observed treatment possible 1, 2
- Preferred when follow-up is unpredictable or compliance with multi-day regimens is questionable 1, 2
- 97% microbial cure rate 2
Treatment Algorithm
For most patients: Prescribe doxycycline 100 mg orally twice daily for 7 days 1, 2, 8
Switch to azithromycin 1 g orally single dose when: 1, 2
- Patient compliance with 7-day regimen is questionable
- Follow-up is unpredictable
- Directly observed therapy is needed
- Patient specifically requests single-dose option
- First choice: Azithromycin 1 g orally single dose
- Alternative: Amoxicillin 500 mg orally three times daily for 7 days
- Contraindicated: Doxycycline, ofloxacin, levofloxacin
Critical Management Components
Sexual Abstinence Requirements:
Patients must abstain from all sexual intercourse for 7 days after initiating treatment AND until all sex partners have completed treatment. 1, 2, 9 This is non-negotiable to prevent reinfection.
Partner Management:
- All sex partners from the preceding 60 days must be evaluated, tested, and empirically treated 1, 2, 9
- Treat the most recent partner even if last sexual contact was >60 days before diagnosis 1, 2
- Failure to treat partners leads to reinfection in up to 20% of cases 1
Medication Dispensing:
Dispense medications on-site when possible and directly observe the first dose to maximize compliance 1, 2
Follow-Up Strategy
Test-of-Cure:
NOT recommended for non-pregnant patients treated with doxycycline or azithromycin unless: 1, 2, 9
- Therapeutic compliance is questionable
- Symptoms persist
- Reinfection is suspected
Testing before 3 weeks post-treatment is unreliable due to false-positive results from dead organisms 1, 9
Reinfection Screening:
All women with chlamydia should be retested approximately 3 months after treatment regardless of whether partners were reportedly treated 1, 2, 9 This is distinct from test-of-cure and screens for reinfection, which carries elevated risk for pelvic inflammatory disease and complications. 1, 9
Special Populations
Rectal Chlamydia:
Doxycycline is definitively superior to azithromycin for rectal chlamydia in men who have sex with men, with cure rates of 96.9-100% versus 71-76.4%. 6, 7 This represents a clinically significant 20-26 percentage point difference. 6, 7
Pregnant Women:
- Azithromycin 1 g single dose is preferred 1, 2
- Amoxicillin 500 mg three times daily for 7 days is the alternative 1, 2
- Test-of-cure is mandatory 3 weeks after treatment completion 9
Children ≥8 years weighing >45 kg:
Use adult dosing: azithromycin 1 g single dose or doxycycline 100 mg twice daily for 7 days 1, 2
Common Pitfalls to Avoid
Never use ceftriaxone alone for chlamydia - it has zero activity against Chlamydia trachomatis 3
Do not assume treatment failure when recurrence occurs - 84-92% of recurrent infections are reinfections from untreated partners, not antibiotic resistance 9
Do not allow sexual activity before partner treatment is complete - both patient and all partners must complete treatment before resuming intercourse 1, 2, 9
Do not skip the 3-month retest in women - this is when reinfection risk is highest and PID risk is elevated 1, 2, 9
Do not test too early after treatment - wait at least 3 weeks to avoid false-positives 1, 9
Concurrent Gonorrhea Consideration
If gonorrhea is confirmed or suspected in high-prevalence populations, always treat for both infections concurrently. 1, 4 Current CDC guidelines recommend ceftriaxone 500 mg IM for gonorrhea PLUS doxycycline 100 mg twice daily for 7 days for presumed chlamydia coinfection. 4