What is the recommended alternative therapy for cat‑scratch disease (Bartonella henselae infection) in a patient with a penicillin allergy manifested by hives?

Alternative Antibiotic for Cat Scratch Disease with Penicillin Allergy

For a patient with cat scratch disease who has a penicillin allergy manifested by hives, azithromycin remains the first-line treatment, as it is a macrolide antibiotic with no cross-reactivity with penicillins. 1

Primary Treatment Recommendation

• Azithromycin is the recommended first-line therapy regardless of penicillin allergy status, as macrolides are structurally unrelated to beta-lactam antibiotics 1
• Dosing for adults (>45 kg): 500 mg on day 1, followed by 250 mg daily for 4 additional days 1, 2
• Dosing for patients <45 kg: 10 mg/kg on day 1, followed by 5 mg/kg daily for 4 additional days 1, 2

Alternative Options if Azithromycin is Unavailable or Contraindicated

If azithromycin cannot be used, the following alternatives are recommended:

First Alternative: Doxycycline

• Doxycycline 100 mg twice daily is the CDC-recommended alternative 1
• This tetracycline antibiotic has no cross-reactivity with penicillins 1
• Treatment duration should be at least 3 months for standard infections 3
• Important caveat: Patients should take doxycycline with adequate liquid and avoid taking it immediately before bedtime to prevent pill-associated esophagitis 3

Second Alternative: Erythromycin

• Erythromycin 500 mg four times daily is another CDC-recommended alternative 1
• This is particularly important for pregnant or breastfeeding women, as it is the only macrolide explicitly endorsed for these populations 1
• Erythromycin is also a first-line agent with demonstrated clinical efficacy 3, 4, 5

Antibiotics to Avoid

Critical pitfall: Do not use the following antibiotics, as they are ineffective against Bartonella:

• Penicillins and first-generation cephalosporins have no in vivo activity against Bartonella and should never be used 1, 3
• Fluoroquinolones and TMP-SMX have variable activity and inconsistent clinical response, and are not recommended as monotherapy 1, 3

Special Considerations Based on Clinical Context

For Pregnant Women

• Erythromycin is the only safe option 1
• Doxycycline is absolutely contraindicated due to fetal toxicity 1
• Fluoroquinolones should be avoided 1

For Severe or Disseminated Disease

• Doxycycline with or without rifampin is the treatment of choice for CNS involvement or other severe infections 1
• Consider gentamicin for hepatosplenic involvement, which has shown 73% efficacy with rapid response within 48 hours 1

For Immunocompromised Patients

• More aggressive treatment is required, with therapy duration exceeding 3 months 1
• Long-term suppression with erythromycin or doxycycline should be considered for relapse prevention 6, 1

Treatment Duration and Monitoring

• Standard uncomplicated cat scratch disease: 5 days of azithromycin 1, 2
• Treatment failure or severe disease: minimum 3 months of doxycycline or erythromycin 3
• Monitor for treatment response within 1-2 weeks; lack of improvement warrants further diagnostic evaluation 3

Key Clinical Pearls

• Most cases in immunocompetent patients are self-limited and may not require antibiotics, but treatment with azithromycin speeds lymph node resolution 1, 7, 8
• The penicillin allergy with hives does not limit your treatment options, as none of the effective antibiotics for cat scratch disease are beta-lactams 1, 3
• Serologic testing may not show detectable antibodies until 6 weeks after infection, so early testing can yield false negatives 1