What is a suitable antibiotic regimen for an adult patient with pneumonia and a known allergy to amoxicillin (amoxicillin)?

Respiratory Fluoroquinolone Monotherapy for Penicillin-Allergic Patients with Pneumonia

For adults with community-acquired pneumonia and documented amoxicillin allergy, use a respiratory fluoroquinolone as monotherapy: levofloxacin 750 mg daily or moxifloxacin 400 mg daily. 1, 2

Outpatient Treatment (Mild-Moderate Severity)

• Levofloxacin 750 mg orally once daily for 5 days is the preferred regimen for outpatients with penicillin allergy, providing excellent coverage against both typical and atypical pathogens including drug-resistant Streptococcus pneumoniae 2, 3
• Moxifloxacin 400 mg orally once daily for 5-7 days serves as an equally effective alternative 2
• Doxycycline 100 mg orally twice daily for 5-7 days can be used if fluoroquinolones are contraindicated (pregnancy, history of tendon disorders, QT prolongation), though this carries lower quality evidence 2

Inpatient Non-ICU Treatment

• Levofloxacin 750 mg IV once daily is the guideline-recommended first-line therapy for hospitalized penicillin-allergic patients, with strong recommendation and level I evidence 1, 2
• Moxifloxacin 400 mg IV once daily provides equivalent efficacy 2
• Transition to oral therapy when hemodynamically stable, afebrile for 48-72 hours, and able to tolerate oral intake—typically by day 2-3 of hospitalization 2
• Total treatment duration should be 5-7 days for uncomplicated pneumonia once clinical stability is achieved 2, 3

ICU-Level Severe Pneumonia

• For penicillin-allergic ICU patients, use aztreonam 2 g IV every 8 hours PLUS levofloxacin 750 mg IV daily to provide dual coverage against gram-negative pathogens and pneumococci 1, 2
• This combination addresses the mandatory requirement for dual therapy in severe CAP while avoiding β-lactam exposure 2
• If Pseudomonas aeruginosa risk factors are present (structural lung disease, recent hospitalization with IV antibiotics within 90 days, prior P. aeruginosa isolation), continue aztreonam plus levofloxacin with consideration for adding an aminoglycoside 2
• If MRSA risk factors exist (prior MRSA infection, post-influenza pneumonia, cavitary infiltrates), add vancomycin 15 mg/kg IV every 8-12 hours or linezolid 600 mg IV every 12 hours 2

Evidence Supporting Fluoroquinolone Use in Penicillin Allergy

The 2007 IDSA/ATS guidelines explicitly state that respiratory fluoroquinolones should be used for penicillin-allergic patients in both outpatient and inpatient settings 1. Levofloxacin demonstrates 95% clinical success rates in community-acquired pneumonia, including infections with multi-drug resistant S. pneumoniae (MDRSP) 3. The drug maintains activity against penicillin-resistant pneumococci with MIC ≥4 mg/L 2.

Critical Clinical Pitfalls to Avoid

• Never use macrolide monotherapy (azithromycin, clarithromycin) for hospitalized patients, even with penicillin allergy, as this provides inadequate coverage for typical bacterial pathogens like S. pneumoniae 2, 4
• In areas where pneumococcal macrolide resistance exceeds 25%, avoid macrolides entirely for empiric therapy 2, 4
• Do not use cephalosporins in patients with documented amoxicillin allergy without allergy testing, as cross-reactivity risk exists—fluoroquinolones avoid this concern entirely 2
• Avoid extending fluoroquinolone therapy beyond 7 days in responding patients, as longer courses increase antimicrobial resistance risk without improving outcomes 2
• Administer the first antibiotic dose immediately upon diagnosis, ideally in the emergency department, as delayed administration beyond 8 hours increases 30-day mortality by 20-30% 2

When Fluoroquinolones Are Contraindicated

If fluoroquinolones cannot be used (pregnancy, pediatric patients, history of fluoroquinolone-associated tendon rupture, significant QT prolongation):

• For outpatients: Doxycycline 100 mg orally twice daily for 5-7 days 2
• For hospitalized non-ICU patients: Aztreonam 2 g IV every 8 hours PLUS azithromycin 500 mg IV daily 2
• For ICU patients: Aztreonam 2 g IV every 8 hours PLUS azithromycin 500 mg IV daily, with vancomycin or linezolid added if MRSA risk factors present 2

Clinical Stability Criteria Before Discharge

Patients must meet all of the following before transitioning to oral therapy or discharge: afebrile for >48 hours, heart rate <100 bpm, respiratory rate <24 breaths/minute, systolic blood pressure >90 mmHg, oxygen saturation >90% on room air, and ability to maintain oral intake 2.