Oral Antibiotics for Gonorrhea
The only recommended oral antibiotic regimen for gonorrhea is cefixime 400 mg orally as a single dose PLUS azithromycin 1 g orally as a single dose, but this is strictly an alternative when intramuscular ceftriaxone is unavailable, and requires mandatory test-of-cure at 1 week. 1, 2
Critical Understanding: Oral Therapy is Second-Line
- Ceftriaxone 500 mg intramuscularly (not oral) remains the gold standard and should be used whenever possible because it achieves superior cure rates, particularly for pharyngeal infections 1, 3
- Oral cefixime has declining effectiveness due to rising minimum inhibitory concentrations (MICs), making it less reliable than intramuscular ceftriaxone 1, 2
The Only Acceptable Oral Regimen
When ceftriaxone is truly unavailable:
- Cefixime 400 mg orally single dose PLUS azithromycin 1 g orally single dose 1, 2, 4
- Mandatory test-of-cure at 1 week is non-negotiable with this regimen due to reduced efficacy 1, 2
Why Dual Therapy is Essential
- Co-infection with Chlamydia trachomatis occurs in 40-50% of gonorrhea patients, making presumptive chlamydia treatment essential 1, 2
- Dual therapy with different mechanisms of action helps delay emergence of cephalosporin resistance 1, 2
- Never use azithromycin 1 g alone - it has only 93% efficacy for gonorrhea 1, 5
Severe Cephalosporin Allergy Alternative
If the patient has documented severe cephalosporin allergy:
- Azithromycin 2 g orally as a single dose 1, 2
- Mandatory test-of-cure at 1 week 1, 2
- Warning: This regimen has lower efficacy (93%) and high gastrointestinal side effects (35% of patients experience GI symptoms, with 2.9% severe) 1, 5
Critical Pitfalls to Avoid
- Never use fluoroquinolones (ciprofloxacin, ofloxacin) - widespread resistance makes them obsolete despite historical 99.8% cure rates 1, 2, 6
- Never use doxycycline as the second agent for gonorrhea treatment - 77.2% of gonococcal isolates with elevated cefixime MICs show tetracycline resistance 6
- Never substitute oral therapy for pharyngeal gonorrhea - pharyngeal infections are significantly more difficult to eradicate and require intramuscular ceftriaxone 1
Site-Specific Considerations
- Pharyngeal gonorrhea: Oral cefixime has substantially lower efficacy than ceftriaxone for pharyngeal infections; strongly prefer intramuscular therapy 1
- Urogenital/anorectal gonorrhea: Oral cefixime achieves 95-98% cure rates when combined with azithromycin 7, 8
Special Populations
- Pregnancy: Use ceftriaxone (intramuscular) plus azithromycin 1 g orally; never use quinolones or tetracyclines 1, 2
- Men who have sex with men (MSM): Do not use oral alternatives - higher prevalence of resistant strains mandates intramuscular ceftriaxone 1, 2
- Recent foreign travel: Intramuscular ceftriaxone only due to higher resistance rates 1
Partner Management
- All sexual partners from the preceding 60 days must be evaluated and treated 1, 2
- Expedited partner therapy option: Oral combination therapy (cefixime 400 mg plus azithromycin 1 g) can be provided if partners cannot access timely evaluation 1
- Partners should receive the same dual therapy regimen 1
Follow-Up Requirements
- With recommended ceftriaxone regimen: No routine test-of-cure needed unless symptoms persist 1, 2
- With oral cefixime regimen: Mandatory test-of-cure at 1 week 1, 2
- All patients: Consider retesting at 3 months due to high reinfection risk 1, 2