What is the recommended treatment for gonorrhea?

Treatment of Gonorrhea

Primary Recommended Regimen

The first-line treatment for uncomplicated gonorrhea is ceftriaxone 500 mg intramuscularly as a single dose, combined with doxycycline 100 mg orally twice daily for 7 days if chlamydial coinfection has not been excluded. 1

This represents an update from previous dual therapy recommendations that included azithromycin, driven by antimicrobial stewardship concerns and rising azithromycin resistance patterns. 1

Alternative Regimens When Ceftriaxone Is Unavailable

If ceftriaxone cannot be obtained:

• Cefixime 400 mg orally once PLUS azithromycin 1 g orally once is the alternative regimen. 2, 3
• Critical caveat: Cefixime is significantly less effective than ceftriaxone, particularly for pharyngeal infections (only 80% cure rate for pharyngeal gonorrhea with gentamicin-based regimens compared to 96% with ceftriaxone). 4
• Mandatory test-of-cure is required 1 week after treatment when using cefixime. 2, 3

Severe Cephalosporin Allergy

For patients with documented severe cephalosporin allergy:

• Azithromycin 2 g orally as a single dose is recommended. 2, 3
• Test-of-cure is mandatory 1 week after treatment. 3
• Note that azithromycin 1 g alone has only 93% efficacy and is insufficient as monotherapy. 3

Site-Specific Considerations

Pharyngeal gonorrhea is substantially more difficult to eradicate than urogenital or anorectal infections. 3

• Ceftriaxone demonstrates superior efficacy for pharyngeal infections compared to all oral alternatives. 3
• In the G-ToG trial, pharyngeal clearance was 96% with ceftriaxone versus only 80% with gentamicin (both combined with azithromycin). 4
• Never substitute oral cefixime for ceftriaxone when treating pharyngeal gonorrhea. 3

Special Populations

Men Who Have Sex With Men (MSM)

• Only ceftriaxone should be used due to higher prevalence of resistant strains in this population. 2, 3
• Quinolones are absolutely contraindicated in MSM. 2, 3

Pregnant Women

• Ceftriaxone is the preferred treatment. 2, 3
• Quinolones and tetracyclines are contraindicated in pregnancy. 2, 3

Recent Foreign Travel

• Ceftriaxone is the only recommended treatment for patients with history of recent foreign travel due to higher likelihood of resistant strains. 3

Rationale for Dual Therapy

The dual therapy approach addresses two critical issues:

• Coinfection with Chlamydia trachomatis occurs in 40-50% of gonorrhea cases, making presumptive treatment essential. 3
• Rising antibiotic resistance patterns necessitate combination therapy to improve efficacy and potentially delay emergence of cephalosporin resistance. 3
• The shift from azithromycin to doxycycline as the preferred second agent reflects antimicrobial stewardship principles and increasing azithromycin resistance. 1

Partner Management

• All sexual partners from the preceding 60 days must be evaluated and treated. 2, 3
• If the last sexual contact was >60 days before symptom onset or diagnosis, treat the most recent partner. 2
• Patients must avoid sexual intercourse until therapy is completed and both partners are asymptomatic. 3
• Expedited partner therapy may be considered when partners' treatment cannot be ensured. 3

Concurrent Testing Requirements

• Screen for syphilis with serology at the time of gonorrhea diagnosis. 2
• Test for other sexually transmitted infections including HIV. 5
• Appropriate cultures for gonorrhea should be performed at diagnosis. 6

Follow-Up and Test-of-Cure

• Patients treated with recommended ceftriaxone regimens do not require routine test-of-cure. 3
• Test-of-cure IS mandatory when using alternative regimens (cefixime, azithromycin monotherapy). 2, 3
• Consider retesting all patients 3 months after treatment due to high reinfection rates (approximately 10% retreatment rate within 2 years). 3, 7
• Patients with persistent symptoms after treatment should be evaluated by culture with antimicrobial susceptibility testing. 3

Critical Pitfalls to Avoid

• Never use quinolones (ciprofloxacin) for gonorrhea treatment due to widespread resistance. 3, 5
• Never use azithromycin 1 g as monotherapy - it has insufficient efficacy at 93%. 3
• Never substitute oral cefixime for pharyngeal infections when ceftriaxone is available. 3
• Do not use the capsule formulation for otitis media treatment, as the suspension achieves higher peak blood levels. 8

Treatment Failure Management

If treatment failure occurs:

• Culture relevant clinical specimens and perform antimicrobial susceptibility testing. 3
• Consult an infectious disease specialist. 3
• Consider alternative diagnoses or reinfection versus true treatment failure. 3