What is the recommended oral treatment regimen for gonorrhea?

Oral Treatment for Gonorrhea

The recommended oral treatment for gonorrhea is cefixime 400 mg orally as a single dose PLUS azithromycin 1 g orally as a single dose, but this should only be used when intramuscular ceftriaxone is unavailable, and requires mandatory test-of-cure at 1 week. 1, 2

Critical Context: Oral Therapy is Second-Line

• Intramuscular ceftriaxone (500 mg IM) remains the preferred first-line treatment because it achieves superior cure rates, particularly for pharyngeal infections 1, 3
• Oral cefixime should be reserved for situations where IM administration is not feasible 1
• Rising cefixime minimum inhibitory concentrations (MICs) have resulted in declining effectiveness compared to ceftriaxone 1

Primary Oral Regimen (When IM Not Available)

Cefixime 400 mg orally single dose PLUS azithromycin 1 g orally single dose 1, 2, 4

• This regimen has demonstrated 96-98% cure rates in clinical trials 5
• The FDA approves cefixime 400 mg as a single oral dose for uncomplicated cervical/urethral gonorrhea 4
• Mandatory test-of-cure at 1 week is required with culture or nucleic acid amplification testing 1, 2
• Cefixime is significantly less effective than ceftriaxone for pharyngeal infections—avoid using oral therapy for pharyngeal gonorrhea 1, 2

Alternative Oral Regimen (Severe Cephalosporin Allergy)

Azithromycin 2 g orally as a single dose 1, 2, 6

• This is the only option for patients with severe cephalosporin allergy who cannot receive IM therapy 1
• Lower efficacy (only 93% cure rate) compared to cephalosporin-based regimens 1
• High gastrointestinal side effects with the 2 g dose 1
• Mandatory test-of-cure at 1 week is required 1, 2
• Never use azithromycin 1 g alone—insufficient efficacy for gonorrhea monotherapy 1

Critical Pitfalls to Avoid

• Never use fluoroquinolones (ciprofloxacin, ofloxacin) for gonorrhea treatment due to widespread resistance, despite their historical effectiveness 1, 7
• Never substitute oral therapy for pharyngeal gonorrhea—ceftriaxone IM is the only reliably effective treatment for pharyngeal infections 1
• Never use azithromycin 1 g as monotherapy for gonorrhea 1
• The oral suspension formulation achieves higher peak blood levels than tablets/capsules at the same dose, so tablets should not be substituted for suspension in otitis media treatment 4

Mandatory Follow-Up Requirements

• Test-of-cure at 1 week is mandatory for all oral regimens (cefixime-based or azithromycin monotherapy) 1, 2
• Culture is preferred for test-of-cure because it allows antimicrobial susceptibility testing 6
• If nucleic acid amplification testing is positive at follow-up, confirm with culture 8
• All positive cultures should undergo phenotypic antimicrobial susceptibility testing 8

Partner Management

• Evaluate and treat all sexual partners from the preceding 60 days 1, 2, 6
• Partners should receive the same dual therapy regimen for both gonorrhea and chlamydia 1
• Patients should avoid sexual intercourse until therapy is completed and both they and their partners are asymptomatic 1, 6
• Consider expedited partner therapy with oral combination therapy (cefixime 400 mg plus azithromycin 1 g) if partners cannot be linked to timely evaluation 8

Treatment Failure Management

• Obtain specimens for culture and antimicrobial susceptibility testing immediately 1, 6
• Report the case to local public health officials within 24 hours 1, 6
• Consult an infectious disease specialist 1, 6
• Salvage regimens include gentamicin 240 mg IM plus azithromycin 2 g orally, or ertapenem 1 g IM for 3 days 1

Special Population Considerations

• Pregnant women: Use ceftriaxone (preferred cephalosporin) plus azithromycin 1 g; never use quinolones or tetracyclines 1, 2
• Men who have sex with men (MSM): Do not use oral therapy—ceftriaxone IM is mandatory due to higher prevalence of resistant strains 1, 2
• Recent foreign travel: Ceftriaxone IM is the only recommended treatment 1

Concurrent Testing and Treatment

• Screen for syphilis with serology at the time of gonorrhea diagnosis 2
• Test for other sexually transmitted infections including HIV 7
• Consider retesting all patients 3 months after treatment due to high risk of reinfection 1
• Co-infection with chlamydia occurs in 40-50% of gonorrhea cases, making dual therapy essential 1