What prophylactic treatment is recommended for chlamydia and gonorrhea (Neisseria gonorrhoeae) following possible Sexually Transmitted Disease (STD) exposure?

Prophylactic Treatment for Chlamydia and Gonorrhea After STD Exposure

For patients with possible STD exposure today, administer ceftriaxone 500 mg IM as a single dose PLUS doxycycline 100 mg orally twice daily for 7 days to cover both gonorrhea and chlamydia prophylactically. 1, 2, 3

Primary Recommendation

The most recent CDC guidelines (2020-2021) recommend dual therapy for empiric treatment when STD exposure has occurred:

• Ceftriaxone 500 mg IM single dose for gonorrhea coverage 2, 3, 4
• Doxycycline 100 mg orally twice daily for 7 days for chlamydia coverage 1, 5, 3, 4

This represents an update from older recommendations that used ceftriaxone 250 mg, as pharmacokinetic data now support the higher 500 mg dose for optimal efficacy 2, 3

Rationale for Dual Therapy

Co-infection rates are extremely high (40-50% of gonorrhea patients also have chlamydia), making presumptive treatment for both organisms essential when empiric therapy is indicated. 1

Key considerations:

• Rising azithromycin resistance in gonorrhea has shifted the preferred chlamydia treatment from azithromycin to doxycycline in this context 2, 3
• Doxycycline provides reliable chlamydia coverage without contributing to macrolide resistance in gonorrhea 3
• Single-dose azithromycin 1g alone is insufficient for gonorrhea (only 93% efficacy) and should never be used as monotherapy 1, 6

Alternative Regimens

If ceftriaxone is unavailable:

• Cefixime 400 mg orally single dose PLUS doxycycline 100 mg twice daily for 7 days 1
• Requires test-of-cure 1 week after treatment due to inferior efficacy 1

For severe cephalosporin allergy:

• Azithromycin 2g orally single dose (covers both organisms but has high GI side effects in 35% of patients) 1, 7
• Test-of-cure required 1 week after treatment 1
• Spectinomycin 2g IM is an option but has poor pharyngeal coverage (only 52% effective) 8, 9

Special Populations

Pregnancy:

• Ceftriaxone 500 mg IM single dose (safe in pregnancy) 8, 1
• Never use doxycycline, quinolones, or tetracyclines in pregnancy 8, 9
• For chlamydia coverage: Azithromycin 1g orally single dose OR Amoxicillin 500 mg three times daily for 7 days 8, 9

Critical Pitfalls to Avoid

• Never use quinolones (ciprofloxacin, ofloxacin) for gonorrhea due to widespread resistance 1, 3
• Never rely on azithromycin 1g alone for gonorrhea treatment (insufficient efficacy) 1, 6
• Do not use spectinomycin if pharyngeal exposure is suspected (only 52% effective at this site) 8, 9
• Avoid using the older 250 mg ceftriaxone dose—current guidelines recommend 500 mg 2, 3, 4

Site-Specific Considerations

Pharyngeal exposure requires special attention:

• Pharyngeal gonorrhea is more difficult to eradicate than urogenital or anorectal infections 1, 9
• Ceftriaxone has superior efficacy for pharyngeal infections compared to oral alternatives 1
• The recommended ceftriaxone 500 mg IM dose reliably achieves >90% cure rates at pharyngeal sites 9

Partner Management and Follow-Up

All sexual partners from the preceding 60 days should be evaluated and treated for both N. gonorrhoeae and C. trachomatis. 8, 1, 9

Additional guidance:

• Patients should avoid sexual intercourse until therapy is completed and both patient and partners are asymptomatic 8, 9
• Routine test-of-cure is not needed for patients treated with recommended regimens unless symptoms persist 8, 1
• Retest all patients approximately 3 months after treatment due to high reinfection risk 1
• If symptoms persist after treatment, culture for N. gonorrhoeae with antimicrobial susceptibility testing is required 1, 9

Antimicrobial Stewardship Context

The shift from dual therapy with azithromycin to doxycycline reflects evolving resistance patterns:

• Azithromycin resistance in gonorrhea rose rapidly to nearly 5% by 2018 3
• Ceftriaxone MICs have remained stable in the US with <0.1% showing elevated values 3
• The 500 mg ceftriaxone dose provides greater margin of safety against potential resistance emergence 2, 3