What is the preferred first‑line oral antibiotic for an adult with acute bacterial sinusitis who has a documented amoxicillin allergy?

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Antibiotic for Sinus Infection with Amoxicillin Allergy

For an adult with acute bacterial sinusitis and documented amoxicillin allergy, prescribe a second‑ or third‑generation cephalosporin (cefuroxime, cefpodoxime, or cefdinir) for 10 days as first‑line therapy, because cross‑reactivity with penicillin is negligible and these agents provide excellent coverage against the major sinusitis pathogens.

Confirm the Diagnosis Before Prescribing Antibiotics

  • Acute bacterial rhinosinusitis (ABRS) should be diagnosed only when at least one of the following patterns is present: persistent symptoms ≥10 days without improvement (purulent nasal discharge plus obstruction or facial pain/pressure), severe symptoms ≥3–4 consecutive days with fever ≥39 °C plus purulent discharge and facial pain, or "double sickening" (initial improvement followed by worsening). 112

  • Approximately 98–99.5 % of acute rhinosinusitis cases are viral and resolve spontaneously within 7–10 days without antibiotics; do not prescribe antibiotics for symptoms lasting <10 days unless severe features are present. 112

First‑Line Antibiotic Choice for Penicillin/Amoxicillin Allergy

For non‑severe (non‑type I) penicillin allergy:

  • Cefuroxime‑axetil, cefpodoxime‑proxetil, cefdinir, or cefprozil for 10 days are the preferred first‑line agents because cross‑reactivity with penicillin is negligible (recent evidence shows the risk of serious allergic reactions to second‑ and third‑generation cephalosporins in penicillin‑allergic patients is negligible). 112

  • These cephalosporins provide excellent coverage against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis, with predicted clinical efficacy comparable to amoxicillin‑clavulanate. 2

  • Cefdinir 300 mg twice daily for 10 days is a commonly used third‑generation option with high patient acceptance. 2

For severe (type I/anaphylactic) penicillin allergy:

  • Levofloxacin 500 mg once daily for 10–14 days or moxifloxacin 400 mg once daily for 10 days are the treatments of choice, providing 90–92 % predicted clinical efficacy against multidrug‑resistant S. pneumoniae and β‑lactamase‑producing organisms. 112

  • Fluoroquinolones are chemically distinct from β‑lactams and exhibit no cross‑reactivity with penicillins, making them safe for patients with documented severe penicillin allergy. 2

Antibiotics to Avoid

  • Azithromycin and other macrolides should not be used due to 20–25 % resistance rates for both S. pneumoniae and H. influenzae; the American Academy of Pediatrics explicitly contraindicates azithromycin for acute bacterial sinusitis. 112

  • Trimethoprim‑sulfamethoxazole has 50 % resistance in S. pneumoniae and 27 % resistance in H. influenzae, making it unsuitable. 2

  • First‑generation cephalosporins (e.g., cephalexin) provide inadequate coverage because approximately 50 % of H. influenzae strains produce β‑lactamase. 2

Treatment Duration and Monitoring

  • Continue therapy for 10 days or until the patient is symptom‑free for 7 consecutive days (typically 10–14 days total). 112

  • Reassess at 3–5 days: if no clinical improvement (persistent purulent drainage, unchanged facial pain, or worsening), switch to a respiratory fluoroquinolone (levofloxacin or moxifloxacin). 112

  • Reassess at 7 days: persistent or worsening symptoms warrant confirmation of diagnosis, exclusion of complications (orbital cellulitis, meningitis, intracranial abscess), and consideration of imaging or ENT referral. 112

Essential Adjunctive Therapies (Add to All Patients)

  • Intranasal corticosteroids (mometasone, fluticasone, or budesonide) twice daily significantly reduce mucosal inflammation and accelerate symptom resolution; this recommendation is supported by strong evidence from multiple randomized controlled trials. 112

  • Saline nasal irrigation 2–3 times daily provides symptomatic relief and aids mucus clearance. 112

  • Analgesics (acetaminophen or ibuprofen) for pain and fever control. 112

Watchful Waiting Option

  • For uncomplicated ABRS with reliable follow‑up, initial observation without antibiotics is appropriate; initiate antibiotics only if no improvement by day 7 or if symptoms worsen at any time. The number needed to treat (NNT) with antibiotics is 10–15 to achieve one additional cure. 112

Critical Pitfalls to Avoid

  • Do not assume all penicillin allergies are severe: most patients with reported penicillin allergy have non‑severe reactions and can safely receive cephalosporins. 12

  • Do not use fluoroquinolones as routine first‑line therapy in patients with non‑severe penicillin allergy; reserve them for severe (type I) allergies or treatment failures to prevent resistance development. 112

  • Do not prescribe antibiotics for symptoms <10 days unless severe criteria (fever ≥39 °C with purulent discharge for ≥3 consecutive days) are met. 112

  • Ensure adequate treatment duration (minimum 10 days for cephalosporins) to prevent relapse. 12

Referral to Otolaryngology

  • Refer if there is no improvement after 7 days of appropriate second‑line antibiotic therapy, worsening symptoms at any point, suspected complications (severe headache, visual changes, periorbital swelling, altered mental status), or recurrent sinusitis (≥3 episodes per year) requiring evaluation for underlying allergic rhinitis, immunodeficiency, or anatomic abnormalities. 112

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Treatment of Acute Bacterial Sinusitis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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