What are the recommended antibiotics for community-acquired pneumonia (CAP) in a patient allergic to Penicillin (PCN)?

Antibiotic Treatment for Community-Acquired Pneumonia in Penicillin-Allergic Patients

For penicillin-allergic patients with community-acquired pneumonia, respiratory fluoroquinolone monotherapy (levofloxacin 750 mg daily or moxifloxacin 400 mg daily) is the preferred first-line treatment for both outpatient and non-ICU hospitalized patients. 1, 2

Outpatient Treatment

• Respiratory fluoroquinolones (levofloxacin 750 mg daily, moxifloxacin 400 mg daily, or gemifloxacin) are the preferred first-line option for penicillin-allergic outpatients with CAP, supported by high-quality evidence and clinical success rates exceeding 90%. 1, 3, 4

• Doxycycline 100 mg twice daily is an acceptable alternative for penicillin-allergic patients who cannot tolerate fluoroquinolones, though this carries lower quality evidence. 5, 1

• Macrolides (azithromycin 500 mg day 1, then 250 mg daily; or clarithromycin 500 mg twice daily) should only be used in areas where pneumococcal macrolide resistance is <25%, as resistance rates now exceed this threshold in many U.S. regions. 5, 1, 6

Non-ICU Hospitalized Patients

• Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg IV/oral daily or moxifloxacin 400 mg IV/oral daily) is the preferred regimen for non-severe CAP in hospitalized penicillin-allergic patients, with strong recommendation and Level I evidence. 2, 3, 4

• Aztreonam 2 g IV every 8 hours PLUS azithromycin 500 mg IV/oral daily is an alternative regimen for patients with contraindications to fluoroquinolones, providing coverage for both typical and atypical pathogens without β-lactam cross-reactivity. 1, 2

• The first antibiotic dose should be administered in the emergency department before hospital admission, as delayed administration beyond 8 hours increases 30-day mortality by 20-30%. 5, 1

ICU Patients (Severe CAP)

• Mandatory combination therapy with respiratory fluoroquinolone (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) PLUS aztreonam 2 g IV every 8 hours is required for severe CAP requiring ICU admission in penicillin-allergic patients. 1, 2

• This regimen provides dual coverage against pneumococcal and gram-negative pathogens required for severe disease while avoiding all β-lactam exposure. 2

Special Pathogen Coverage

MRSA Coverage

• Add vancomycin 15 mg/kg IV every 8-12 hours (target trough 15-20 mg/mL) OR linezolid 600 mg IV every 12 hours if MRSA is suspected based on: post-influenza pneumonia, cavitary infiltrates on imaging, prior MRSA infection/colonization, or recent hospitalization with IV antibiotics. 1, 2

Pseudomonas Coverage

• Use antipseudomonal fluoroquinolone (levofloxacin 750 mg or ciprofloxacin 400 mg IV every 8 hours) PLUS aztreonam 2 g IV every 8 hours PLUS aminoglycoside (gentamicin or tobramycin 5-7 mg/kg IV daily) for patients with risk factors including: structural lung disease, bronchiectasis, severe COPD with frequent steroid/antibiotic use, or prior P. aeruginosa isolation. 1, 2

Treatment Duration and Transition

• Treat for a minimum of 5 days and until the patient is afebrile for 48-72 hours with no more than one sign of clinical instability, with typical duration of 5-7 days for uncomplicated CAP. 5, 2

• Extend treatment to 14-21 days for confirmed Legionella pneumophila, Staphylococcus aureus, or gram-negative enteric bacilli. 5, 2

• Switch from IV to oral therapy when the patient is hemodynamically stable, clinically improving, able to take oral medications, and has normal GI function—typically by day 2-3 of hospitalization. 5, 1

• Levofloxacin and moxifloxacin are bioequivalent between IV and oral formulations, allowing seamless transition without dose adjustment. 3, 4, 7

Critical Pitfalls to Avoid

• Never use cephalosporins (ceftriaxone, cefotaxime, ceftaroline, cefepime) in patients with documented penicillin allergy due to cross-reactivity concerns, particularly in patients with type I hypersensitivity reactions. 1, 2

• Avoid macrolide monotherapy in hospitalized penicillin-allergic patients, as this provides inadequate coverage for typical bacterial pathogens like S. pneumoniae and resistance rates exceed 25% in many areas. 5, 2

• Do not automatically escalate to broad-spectrum antibiotics based solely on penicillin allergy without documented risk factors for MRSA or Pseudomonas. 5, 1

• Obtain blood and sputum cultures before initiating antibiotics in all hospitalized patients to allow pathogen-directed therapy and de-escalation. 5, 2