What is the recommended empiric treatment regimen for chlamydia (Chlamydia trachomatis) and gonorrhea (Neisseria gonorrhoeae)?

Empiric Treatment for Chlamydia and Gonorrhea

Primary Recommendation

For empiric treatment of suspected chlamydia and gonorrhea co-infection, administer ceftriaxone 500 mg IM as a single dose PLUS doxycycline 100 mg orally twice daily for 7 days. 1

This dual therapy approach addresses both pathogens effectively while accounting for current antimicrobial resistance patterns and the high frequency of co-infection.

Rationale for Dual Therapy

• Co-infection is extremely common - up to 40-50% of patients with gonorrhea also have chlamydia, making presumptive treatment for both organisms essential when empiric therapy is indicated 2

• Doxycycline is now preferred over azithromycin for chlamydial coverage due to rising azithromycin resistance in N. gonorrhoeae and antimicrobial stewardship concerns 1

• The ceftriaxone dose was increased from 250 mg to 500 mg in 2020 to maintain efficacy against evolving gonococcal resistance patterns 1

Alternative Regimens

If Ceftriaxone is Unavailable

• Cefixime 400 mg orally as a single dose PLUS doxycycline 100 mg orally twice daily for 7 days 3, 4
• Cefixime has 96-98% cure rates for urogenital gonorrhea but slightly lower efficacy than ceftriaxone 4
• A test-of-cure is mandatory 1 week after treatment when using cefixime due to rising MICs 3

For Severe Cephalosporin Allergy

• Azithromycin 2 g orally as a single dose 3, 5
• This regimen treats both gonorrhea (98.9% efficacy) and chlamydia simultaneously 5
• Gastrointestinal side effects occur in 35% of patients (moderate in 10%, severe in 3%) 5
• Test-of-cure is required 1 week after treatment 3

Important Clinical Considerations

Site-Specific Efficacy

• Pharyngeal gonorrhea is significantly more difficult to eradicate than urogenital or anorectal infections 3
• Ceftriaxone has superior efficacy for pharyngeal infections compared to oral alternatives 3
• If pharyngeal infection is suspected, ceftriaxone is strongly preferred over cefixime 2

Special Populations

• Pregnant women should receive ceftriaxone (preferred cephalosporin) PLUS azithromycin 1 g orally as a single dose - avoid quinolones and tetracyclines entirely 3, 6

• Men who have sex with men (MSM) should only receive ceftriaxone-based regimens due to higher prevalence of resistant strains 3

• Patients with recent foreign travel should only receive ceftriaxone-based regimens due to geographic resistance patterns 3

Partner Management

• All sexual partners from the preceding 60 days must be evaluated and treated with the same regimen as the index patient 3, 6

• Patients must abstain from sexual intercourse until therapy is completed and both they and their partners are asymptomatic 3, 6

• Expedited partner therapy may be considered if partners' treatment cannot otherwise be ensured 3

Follow-Up Recommendations

• Routine test-of-cure is NOT required for patients treated with the recommended ceftriaxone plus doxycycline regimen who become asymptomatic 3

• Patients with persistent symptoms after treatment must be re-evaluated with culture for N. gonorrhoeae and antimicrobial susceptibility testing 3, 6

• Consider retesting all patients 3 months after treatment due to high reinfection rates (not treatment failure) 3

Critical Pitfalls to Avoid

• Never use quinolones (ciprofloxacin, ofloxacin) for gonorrhea treatment - widespread resistance makes these obsolete despite older guidelines recommending them 2, 3

• Azithromycin 1 g alone is insufficient for gonorrhea with only 93% efficacy and should never be used as monotherapy 3

• Do not use cefixime in MSM or patients with pharyngeal infection - ceftriaxone is mandatory in these populations 3

• Always treat for chlamydia when treating gonorrhea empirically unless chlamydial infection has been definitively excluded by testing 1