What is the recommended treatment for gonorrhea in patients with an anaphylactic allergy to penicillin (PCN)?

Treatment for Gonorrhea in Patients with Anaphylactic Penicillin Allergy

For patients with severe cephalosporin allergy or anaphylactic penicillin allergy, azithromycin 2 g orally as a single dose is the recommended alternative treatment, with mandatory test-of-cure at 1 week. 1

Primary Treatment Approach

First-Line Consideration: Cephalosporins Despite Penicillin Allergy

• Most patients reporting penicillin allergy can safely receive cephalosporins, as true cross-reactivity between penicillin and third-generation cephalosporins is minimal (less than 1-3%). 2
• The standard dual therapy regimen—ceftriaxone 250 mg IM plus azithromycin 1 g orally—remains the preferred treatment even in patients with reported penicillin allergy, unless the allergy is severe or anaphylactic. 1
• Ceftriaxone has no documented cross-reactivity with penicillin in clinical practice and has never had a resistant strain reported. 1, 3

When to Avoid Cephalosporins

• Avoid cephalosporins only in patients with documented anaphylactic reactions to penicillin (angioedema, bronchospasm, hypotension, or anaphylaxis). 1
• Patients with severe delayed-type allergies to beta-lactams should avoid all beta-lactam antibiotics. 4

Alternative Regimen for True Severe Allergy

Recommended Alternative

• Azithromycin 2 g orally in a single dose is the only alternative for patients who cannot receive cephalosporins due to severe allergy. 1
• This regimen is expensive and causes gastrointestinal distress frequently, but remains effective against uncomplicated gonococcal infection. 1

Critical Follow-Up Requirements

• Mandatory test-of-cure at 1 week after treatment using culture or NAAT at the infected anatomic site. 1
• If culture is available, it is preferred over NAAT for test-of-cure to allow antimicrobial susceptibility testing. 1
• All positive cultures should undergo phenotypic antimicrobial susceptibility testing. 1

Historical Alternative: Spectinomycin (No Longer Available)

• Older guidelines recommended spectinomycin 2 g IM for patients unable to tolerate cephalosporins or quinolones. 1
• Spectinomycin is unreliable for pharyngeal infections (only 52% effective) and required pharyngeal culture 3-5 days after treatment. 1
• This agent is no longer available in the United States and should not be considered. 1

Quinolones: Not Recommended

• Fluoroquinolones (ciprofloxacin, ofloxacin, levofloxacin) are no longer recommended due to widespread quinolone-resistant N. gonorrhoeae. 1
• Historical guidelines included quinolones as alternatives, but resistance patterns have eliminated them as viable options. 1

Treatment Algorithm for Penicillin-Allergic Patients

1. Assess allergy severity: Distinguish between non-severe reactions (rash, mild GI upset) versus anaphylactic reactions (angioedema, bronchospasm, hypotension). 1

2. For non-anaphylactic penicillin allergy:

   • Proceed with standard ceftriaxone 250 mg IM plus azithromycin 1 g orally. 1
   • Cross-reactivity risk is minimal and does not justify avoiding first-line therapy. 2

3. For anaphylactic penicillin allergy or documented severe cephalosporin allergy:

   • Use azithromycin 2 g orally as a single dose. 1
   • Schedule test-of-cure at 1 week. 1
   • Counsel patient about high likelihood of gastrointestinal side effects. 1

4. If treatment failure occurs after azithromycin:

   • Retreat with ceftriaxone 250 mg IM plus azithromycin 2 g orally. 1
   • Obtain infectious disease consultation. 1
   • Report case to CDC through local/state health department. 1

Special Considerations

Pharyngeal Gonorrhea

• Pharyngeal infections are more difficult to eradicate than urogenital or anorectal infections. 1
• Azithromycin 2 g has limited data for pharyngeal gonorrhea efficacy. 1
• Test-of-cure is especially critical for pharyngeal infections in penicillin-allergic patients. 1

Pregnancy

• Pregnant women with penicillin allergy should receive cephalosporins unless allergy is severe. 1
• Quinolones and tetracyclines are contraindicated in pregnancy. 1
• If cephalosporins cannot be used, azithromycin 2 g orally is the only option, though data in pregnancy are limited. 1

Concurrent Chlamydia Treatment

• Always treat presumptively for chlamydia when treating gonorrhea, as coinfection is common. 1
• The azithromycin component of dual therapy covers chlamydia. 1
• If using azithromycin 2 g for gonorrhea, this dose also treats chlamydia. 1

Common Pitfalls to Avoid

• Do not withhold cephalosporins based solely on patient-reported penicillin allergy without assessing severity—most patients can safely receive ceftriaxone. 2
• Do not use azithromycin 1 g for gonorrhea treatment—this dose is insufficiently effective, curing only 93% of infections. 1
• Do not skip test-of-cure when using alternative regimens—treatment failure rates are higher with non-cephalosporin regimens. 1
• Do not use fluoroquinolones—resistance is widespread and these are no longer viable alternatives. 1
• Attending physicians are significantly less likely to prescribe appropriate cephalosporins to penicillin-allergic patients compared to teams with residents or physician assistants, suggesting knowledge gaps. 2