What is the recommended treatment for a patient with gonorrhea who cannot be treated with ceftriaxone (Ceftriaxone)?

Alternative Treatment for Gonorrhea When Ceftriaxone is Unavailable

For patients who cannot receive ceftriaxone, the CDC recommends cefixime 400 mg orally plus azithromycin 1 g orally as a single dose, with mandatory test-of-cure at 1 week. 1

Primary Alternative Regimen

• Cefixime 400 mg orally (single dose) PLUS azithromycin 1 g orally (single dose) is the first-line alternative when ceftriaxone is unavailable 1
• This regimen requires mandatory test-of-cure at 1 week after treatment 1, 2
• Culture is the preferred method for test-of-cure as it allows antimicrobial susceptibility testing 2, 3

For Severe Cephalosporin Allergy

If the patient has a severe cephalosporin allergy, the CDC recommends:

• Azithromycin 2 g orally (single dose) as the alternative treatment 1, 3
• This regimen has lower efficacy (93%) compared to ceftriaxone-based therapy 1
• High gastrointestinal side effects occur frequently with this dose 1, 4
• Mandatory test-of-cure at 1 week is required 1, 3
• Consult an infectious disease specialist when using this regimen due to limited data 3

Additional Alternative Regimen

• Gentamicin 240 mg IM (single dose) PLUS azithromycin 2 g orally (single dose) achieved 100% cure rates in clinical trials 1, 5
• This is particularly useful for patients with cephalosporin allergy 5
• Gastrointestinal adverse events are common with this regimen 5

Critical Site-Specific Considerations

Pharyngeal gonorrhea is significantly more difficult to eradicate and requires special attention:

• Ceftriaxone has superior efficacy for pharyngeal infections compared to all alternatives 1
• Spectinomycin has only 52% efficacy for pharyngeal infections and should be avoided 1, 2
• Gentamicin has only 20% cure rate for pharyngeal gonorrhea 1
• Cefixime-based regimens have demonstrated treatment failures specifically at pharyngeal sites 6

Regimens to Avoid

• Never use quinolones (ciprofloxacin, ofloxacin) due to widespread resistance 1, 7
• Never use azithromycin 1 g alone due to insufficient efficacy (only 93%) 1
• Spectinomycin 2 g IM has poor pharyngeal efficacy (52%) despite 98.2% efficacy for urogenital infections 1, 2

Concurrent Chlamydia Treatment

• All patients should be treated for presumptive chlamydia co-infection given 40-50% co-infection rates 1
• If using cefixime or gentamicin regimens (which include azithromycin 1-2 g), chlamydia is covered 1, 8
• If using azithromycin 2 g monotherapy for gonorrhea, chlamydia is also covered 8

Mandatory Follow-Up Requirements

• Test-of-cure at 1 week is required for all alternative regimens (cefixime-based or azithromycin monotherapy) 1, 2, 3
• Culture is preferred over NAAT for test-of-cure to allow antimicrobial susceptibility testing 2, 3
• If NAAT is positive at follow-up, confirm with culture and perform susceptibility testing 1

Treatment Failure Management

If treatment failure occurs:

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

Partner Management

• Evaluate and treat all sexual partners from the preceding 60 days 1, 2, 3
• Partners should receive the same dual therapy regimen for both gonorrhea and chlamydia 1
• Expedited partner therapy with oral cefixime 400 mg plus azithromycin 1 g may be considered if partners cannot be linked to timely evaluation 1, 3
• Patients should avoid sexual intercourse until therapy is completed and both they and their partners are asymptomatic 2, 3

Special Populations

Pregnant women:

• Use cefixime 400 mg orally PLUS azithromycin 1 g orally if injection is refused 1
• Never use quinolones, tetracyclines, or doxycycline in pregnancy 1, 3

Men who have sex with men (MSM):

• Higher prevalence of resistant strains makes alternative regimens less reliable 1
• Do not use expedited partner therapy in MSM due to high risk of undiagnosed coexisting STDs or HIV 1

Common Pitfalls to Avoid

• Do not rely on cefixime for pharyngeal gonorrhea without close follow-up, as treatment failures are more common at this site 1, 6
• Do not skip the test-of-cure when using alternative regimens 1, 2, 3
• Do not use azithromycin 2 g monotherapy as routine first-line due to lower efficacy and high GI side effects 1, 4
• Always screen for syphilis and HIV at the time of gonorrhea diagnosis 1