Recommended Antibiotic for Bacterial Pneumonia with Amoxicillin Allergy
For an outpatient with documented β-lactam allergy and no comorbidities, doxycycline 100 mg orally twice daily for 5–7 days is the preferred first-line alternative to amoxicillin. 1
First-Line Recommendation: Doxycycline
Doxycycline 100 mg orally twice daily for 5–7 days is the guideline-recommended alternative for previously healthy adults with β-lactam allergy, providing coverage of both typical bacterial pathogens (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis) and atypical organisms (Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella pneumophila). 1
Doxycycline retains reliable activity against the predominant causative organisms in community-acquired pneumonia and is supported by moderate-quality evidence as an acceptable alternative when β-lactams cannot be used. 1
Alternative Option: Respiratory Fluoroquinolone (Reserved Use)
Levofloxacin 750 mg orally once daily or moxifloxacin 400 mg orally once daily for 5–7 days may be used when doxycycline is contraindicated (e.g., pregnancy, children < 8 years, known doxycycline allergy). 1
Respiratory fluoroquinolones demonstrate >98% activity against S. pneumoniae (including penicillin-resistant strains) and provide comprehensive coverage of typical and atypical pathogens. 1
However, fluoroquinolones should be reserved for specific situations due to FDA warnings about serious adverse events (tendon rupture, peripheral neuropathy, aortic dissection, QT prolongation) and rising resistance concerns. 1
Macrolides: Conditional Use Only
Macrolide monotherapy (azithromycin 500 mg day 1, then 250 mg daily days 2–5; or clarithromycin 500 mg twice daily) should only be used when local pneumococcal macrolide resistance is documented to be <25%. 1
In most U.S. regions, macrolide resistance among S. pneumoniae is 20–30%, rendering macrolide monotherapy unsafe as first-line therapy in β-lactam-allergic patients. 1, 2
Macrolide-resistant S. pneumoniae is associated with breakthrough bacteremia and treatment failure, making doxycycline or fluoroquinolones safer alternatives in areas with high resistance. 1, 2
Treatment Duration and Monitoring
Minimum treatment duration is 5 days, continuing until the patient is afebrile for 48–72 hours with no more than one sign of clinical instability. 1
Typical total course for uncomplicated pneumonia is 5–7 days. 1
Arrange a clinical review at 48 hours (or sooner if symptoms worsen) to assess response, oral intake, and adherence. 1
Escalation Criteria (When to Refer for Hospitalization)
Indicators of treatment failure warranting hospital referral include:
- No clinical improvement by day 2–3
- Development of respiratory distress (respiratory rate >30/min, oxygen saturation <92%)
- Inability to tolerate oral antibiotics (vomiting, GI dysfunction)
- New complications such as pleural effusion or sepsis 1
If doxycycline monotherapy fails, switch to a respiratory fluoroquinolone (levofloxacin 750 mg daily or moxifloxacin 400 mg daily). 1
Critical Pitfalls to Avoid
Do not use oral cephalosporins (cefuroxime, cefpodoxime, cefixime) in patients with documented amoxicillin allergy due to 1–10% cross-reactivity risk with penicillins; cephalosporins should be avoided unless the penicillin allergy has been definitively excluded. 1
Avoid macrolide monotherapy in regions where pneumococcal macrolide resistance exceeds 25% (the situation in most of the United States), as this increases risk of treatment failure. 1, 2
Do not use fluoroquinolones as routine first-line therapy in uncomplicated outpatient pneumonia; reserve them for doxycycline contraindications or treatment failure to limit resistance and adverse events. 1
Never assume all β-lactam allergies are true IgE-mediated reactions; if the allergy history is unclear (e.g., remote childhood rash, family history only), consider allergy testing or graded challenge before permanently excluding all β-lactams, as this significantly limits future treatment options. 1
Follow-Up and Prevention
Routine follow-up at 6 weeks for all patients; obtain a chest radiograph only if symptoms persist, physical signs remain abnormal, or the patient has high risk for underlying malignancy (e.g., smokers >50 years). 1
Offer pneumococcal polysaccharide vaccination to all adults ≥65 years and those with high-risk conditions. 1
Recommend annual influenza vaccination for all patients. 1
Provide smoking-cessation counseling to every current smoker. 1