What are the appropriate first‑line oral antibiotics for an adult with acute bacterial sinusitis who has a documented penicillin allergy?

Antibiotics for Acute Bacterial Sinusitis in Penicillin-Allergic Adults

For adults with acute bacterial sinusitis and documented penicillin allergy, second- or third-generation cephalosporins (cefuroxime, cefpodoxime, or cefdinir) are the preferred first-line oral antibiotics, with respiratory fluoroquinolones (levofloxacin or moxifloxacin) reserved for patients with severe type I hypersensitivity reactions. 1

Classify the Penicillin Allergy First

Before selecting an antibiotic, determine the type of penicillin reaction:

• Non-severe (non-type I) allergy includes delayed rash, mild gastrointestinal upset, or other non-life-threatening reactions. Recent evidence demonstrates that cross-reactivity between penicillins and second- or third-generation cephalosporins is negligible in these patients. 1, 2

• Severe (type I) allergy includes anaphylaxis, angioedema, bronchospasm, or urticaria occurring immediately after penicillin exposure. These patients require fluoroquinolones rather than cephalosporins due to potential cross-reactivity with the beta-lactam ring. 3

First-Line Options for Non-Severe Penicillin Allergy

Use second- or third-generation cephalosporins as your first choice:

• Cefuroxime-axetil (second-generation): standard dosing for 10 days 1, 4
• Cefpodoxime-proxetil (third-generation): 200 mg twice daily for 10 days 1, 2
• Cefdinir (third-generation): 300 mg twice daily for 10 days 1, 2
• Cefprozil (second-generation): alternative option for 10 days 1

These agents provide excellent coverage against the three major sinusitis pathogens: Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. 4 Third-generation cephalosporins offer superior activity against H. influenzae compared to second-generation agents. 1

First-Line Options for Severe (Type I) Penicillin Allergy

Respiratory fluoroquinolones are the treatment of choice when cephalosporins must be avoided:

• Levofloxacin 500 mg once daily for 10–14 days OR 750 mg once daily for 5 days 1, 3, 5
• Moxifloxacin 400 mg once daily for 10 days 1, 3

Both regimens achieve 90–92% predicted clinical efficacy against all major sinusitis pathogens, including multidrug-resistant S. pneumoniae. 1, 3 The 5-day high-dose levofloxacin regimen (750 mg) has been shown in clinical trials to be non-inferior to the 10-day standard-dose regimen (500 mg). 5

Alternative Option: Doxycycline (Suboptimal)

Doxycycline 100 mg once daily for 10 days is an acceptable but inferior alternative for penicillin-allergic patients. 1 However, doxycycline has significant limitations:

• Predicted bacteriologic failure rate of 20–25% compared to 8–10% for amoxicillin-clavulanate 1
• Limited activity against H. influenzae (30–40% of strains produce beta-lactamase) 1, 4
• Inadequate coverage of penicillin-resistant pneumococci 1

Use doxycycline only when both cephalosporins and fluoroquinolones are contraindicated or unavailable. 1

Antibiotics to Avoid

• Azithromycin and other macrolides have resistance rates exceeding 20–25% for both S. pneumoniae and H. influenzae, making them unsuitable for first-line therapy. 1, 6

• Trimethoprim-sulfamethoxazole shows approximately 50% resistance in S. pneumoniae and 27% in H. influenzae. 1

• First-generation cephalosporins (cephalexin, cefadroxil) provide inadequate coverage because nearly 50% of H. influenzae strains produce beta-lactamase. 1

Confirm the Diagnosis Before Prescribing

Antibiotics should only be prescribed when acute bacterial sinusitis is confirmed by at least one of these clinical patterns:

• Persistent symptoms ≥10 days with purulent nasal discharge plus nasal obstruction or facial pain/pressure 1, 7
• Severe symptoms ≥3–4 consecutive days with fever ≥39°C, purulent discharge, and facial pain 1
• "Double sickening" – worsening after initial improvement from a viral upper respiratory infection 1

Approximately 98–99.5% of acute rhinosinusitis cases are viral and resolve spontaneously within 7–10 days without antibiotics. 1, 7

Essential Adjunctive Therapies (Add to All Patients)

• Intranasal corticosteroids (mometasone, fluticasone, or budesonide) twice daily reduce mucosal inflammation and improve symptom resolution; supported by strong evidence from multiple randomized controlled trials. 1

• Saline nasal irrigation 2–3 times daily provides symptomatic relief and aids mucus clearance. 1

• Analgesics (acetaminophen or ibuprofen) for pain and fever control. 1

Treatment Monitoring and Reassessment

• Reassess at 3–5 days: If no clinical improvement, switch to high-dose amoxicillin-clavulanate (if allergy permits after further evaluation) or escalate to a respiratory fluoroquinolone. 1

• Reassess at 7 days: If symptoms persist or worsen, reconfirm the diagnosis, exclude complications (orbital cellulitis, meningitis, brain abscess), and consider imaging or ENT referral. 1, 3

Common Pitfalls to Avoid

• Do not use cephalosporins in patients with documented anaphylaxis to penicillin – the 1–10% cross-reactivity risk is unacceptable in true type I hypersensitivity. 2, 3

• Do not reserve fluoroquinolones for treatment failures in severe penicillin allergy – they should be first-line when cephalosporins are contraindicated. 3

• Do not prescribe antibiotics for symptoms <10 days unless severe features (fever ≥39°C with purulent discharge for ≥3 consecutive days) are present. 1

• Ensure adequate treatment duration (minimum 5 days for fluoroquinolones, 10 days for cephalosporins) to prevent relapse. 1, 8