What can I prescribe for a respiratory infection in a patient allergic to penicillin, cipro (ciprofloxacin), keflex (cephalexin), erythromycin, and sulfa (sulfonamides)?

Antibiotic Options for Respiratory Infections in Patients with Multiple Allergies

For a patient allergic to penicillin, ciprofloxacin, cephalexin, erythromycin, and sulfa drugs, doxycycline is the most appropriate first-line antibiotic for respiratory infections, with respiratory fluoroquinolones (levofloxacin, moxifloxacin, or gatifloxacin) as alternatives if doxycycline cannot be used. 1

Outpatient Respiratory Infections

Previously Healthy Patients

• Doxycycline is explicitly recommended as an alternative macrolide substitute for community-acquired pneumonia in outpatients 1
• Standard dosing: 100 mg twice daily orally 1
• This covers typical respiratory pathogens including Streptococcus pneumoniae, Haemophilus influenzae, and atypical organisms 1

Patients with Comorbidities (COPD, diabetes, renal/heart failure, malignancy)

• Respiratory fluoroquinolones (levofloxacin 750 mg daily, moxifloxacin 400 mg daily, or gatifloxacin) are preferred when doxycycline is insufficient 1
• These agents provide broader coverage and are specifically recommended for penicillin-allergic patients with comorbidities 1

Hospitalized Patients (Non-ICU)

A respiratory fluoroquinolone alone is the recommended regimen for penicillin-allergic patients requiring hospitalization 1

• Levofloxacin 750 mg IV/PO daily or moxifloxacin 400 mg IV/PO daily 1
• This provides adequate coverage for S. pneumoniae, H. influenzae, and atypical pathogens without requiring combination therapy 1

ICU-Level Respiratory Infections

Without Pseudomonas Risk

• Respiratory fluoroquinolone with or without clindamycin for β-lactam allergic patients 1
• Clindamycin (600 mg IV every 8 hours) added if aspiration or anaerobic coverage needed 1

With Pseudomonas Risk

• Aztreonam plus levofloxacin (750 mg dose) is the preferred regimen for β-lactam allergic patients 1
• Alternative: Aztreonam plus moxifloxacin or gatifloxacin, with or without an aminoglycoside 1
• Aztreonam is a monobactam that does not cross-react with penicillin allergies and provides antipseudomonal coverage 1

Critical Considerations

Why These Options Work for Your Patient

Doxycycline advantages:

• No cross-reactivity with any of the patient's listed allergies 1
• Effective against common respiratory pathogens 1
• Well-tolerated with primarily gastrointestinal side effects 1
• Avoid in children under 8 years due to tooth discoloration risk 1

Respiratory fluoroquinolone advantages:

• Levofloxacin and moxifloxacin are distinct from ciprofloxacin in their respiratory pathogen coverage 1
• While the patient is allergic to ciprofloxacin, this does not automatically preclude other fluoroquinolones unless there was a severe reaction (anaphylaxis, Stevens-Johnson syndrome) 1
• Important caveat: If the ciprofloxacin allergy was an immediate hypersensitivity reaction, avoid all fluoroquinolones and use doxycycline or aztreonam-based regimens instead 1

What NOT to Use

Avoid these options entirely:

• Macrolides (azithromycin, clarithromycin) - patient is allergic to erythromycin, suggesting macrolide class allergy 1, 2
• Trimethoprim-sulfamethoxazole - patient has sulfa allergy 1
• All β-lactams (penicillins, cephalosporins, carbapenems except aztreonam) - patient has penicillin and cephalexin allergies 1, 2
• Ciprofloxacin - documented allergy 1

Resistance Considerations

• Macrolide resistance rates among respiratory pathogens range from 20-41% in some regions, which further supports avoiding this class even if allergy status were unclear 1, 3, 4
• Doxycycline maintains good activity against most community-acquired respiratory pathogens 1
• Respiratory fluoroquinolones have excellent activity against drug-resistant S. pneumoniae 1

Severity-Based Algorithm

1. Mild outpatient infection: Doxycycline 100 mg PO twice daily 1
2. Moderate outpatient or recent antibiotic use: Respiratory fluoroquinolone (if ciprofloxacin allergy was not severe/immediate) 1
3. Hospitalized non-ICU: Respiratory fluoroquinolone IV 1
4. ICU without Pseudomonas: Respiratory fluoroquinolone ± clindamycin 1
5. ICU with Pseudomonas risk: Aztreonam plus levofloxacin or moxifloxacin 1

Duration of Therapy

• Typical duration is 5-7 days for uncomplicated community-acquired pneumonia when clinical stability is achieved 1
• Extend to 10-14 days for severe infections or slow clinical response 1