What is a suitable antibiotic for a patient with a history of allergy to Augmentin (amoxicillin-clavulanate) and Keflex (cephalexin) for the treatment of sinusitis?

Antibiotic Selection for Sinusitis with Augmentin and Keflex Allergy

Primary Recommendation

For a patient allergic to both Augmentin (amoxicillin-clavulanate) and Keflex (cephalexin), a respiratory fluoroquinolone—specifically levofloxacin 500 mg once daily or moxifloxacin 400 mg once daily for 10 days—is the preferred first-line treatment for acute bacterial sinusitis. 1, 2

This recommendation assumes the patient has a true Type I hypersensitivity (anaphylaxis) to penicillin, which contraindicates all beta-lactam antibiotics including cephalosporins due to 1-10% cross-reactivity risk. 2, 3

Understanding the Allergy Profile

The critical first step is determining the type of allergic reaction to these medications:

• If the patient had a non-Type I reaction (rash, mild delayed reaction) to penicillin, second- or third-generation cephalosporins with dissimilar side chains can be used safely, as recent evidence shows negligible cross-reactivity risk. 1, 2
• If the patient had anaphylaxis or Type I hypersensitivity, all beta-lactam antibiotics must be avoided, making fluoroquinolones the primary option. 2, 3

Since the patient reports allergy to both Augmentin (a penicillin) and Keflex (a first-generation cephalosporin), this suggests either true beta-lactam allergy or multiple drug sensitivities requiring fluoroquinolone therapy. 1, 2

Specific Fluoroquinolone Dosing

Levofloxacin 500 mg once daily for 10-14 days provides 90-92% predicted clinical efficacy with excellent coverage against drug-resistant Streptococcus pneumoniae and beta-lactamase-producing Haemophilus influenzae. 1, 2, 3

Moxifloxacin 400 mg once daily for 10 days offers equivalent coverage and efficacy. 1, 2, 3

Both regimens achieve superior outcomes compared to all other available options in penicillin-allergic patients. 3

Why NOT Other Antibiotics

Avoid macrolides (azithromycin, clarithromycin) despite their historical use in penicillin allergy—resistance rates now exceed 40% for S. pneumoniae in the United States and 20-25% overall, making treatment failure likely. 1, 2, 3 While older studies from the 1990s showed comparable efficacy 4, 5, 6, and a recent 2025 meta-analysis demonstrated 70.86% cure rates with azithromycin 7, current guidelines explicitly contraindicate macrolides as first-line therapy due to evolving resistance patterns. 1, 2

Avoid trimethoprim-sulfamethoxazole (Bactrim) due to 50% resistance rates for S. pneumoniae and 27% for H. influenzae. 1, 2

Avoid doxycycline as it has a predicted bacteriologic failure rate of 20-25% and limited activity against H. influenzae due to pharmacokinetic limitations. 1

Avoid first-generation cephalosporins (like Keflex) as they have inadequate coverage against H. influenzae, with nearly 50% of strains being beta-lactamase producing. 1

Alternative Option: Higher-Generation Cephalosporins (If Non-Severe Allergy)

If the patient's allergy to Keflex was a non-Type I reaction (not anaphylaxis), consider:

• Cefpodoxime 200 mg twice daily for 10 days 1, 2
• Cefdinir 300 mg twice daily for 10 days 1, 2
• Cefuroxime axetil 250-500 mg twice daily for 10 days 1, 2

These second- and third-generation cephalosporins have dissimilar side chains to cephalexin and provide superior activity against H. influenzae while maintaining adequate S. pneumoniae coverage. 1, 2 Recent evidence shows the risk of serious allergic reactions to these agents in penicillin-allergic patients is almost nil. 1, 2

Treatment Duration and Monitoring

• Standard duration: 10-14 days or until symptom-free for 7 days 1, 2, 3
• Reassess at 3-5 days: If no improvement, re-evaluate diagnosis or consider complications 1, 2, 3
• Reassess at 7 days: If symptoms persist or worsen, confirm diagnosis and consider referral 1, 2

Most patients should experience noticeable improvement within 3-5 days of starting appropriate antibiotic therapy. 1

Essential Adjunctive Therapies

Intranasal corticosteroids (mometasone, fluticasone, or budesonide twice daily) are strongly recommended to reduce mucosal inflammation and improve symptom resolution, with strong evidence from multiple randomized controlled trials. 1, 2, 3

Saline nasal irrigation provides symptomatic relief and improves sinus drainage. 1, 3

Analgesics (acetaminophen or NSAIDs) for pain and fever management. 1

Critical Pitfalls to Avoid

• Never use fluoroquinolones as first-line therapy in patients without documented beta-lactam allergies—this promotes antimicrobial resistance. 1, 2
• Do not prescribe antibiotics for symptoms lasting <10 days unless severe symptoms are present (fever ≥39°C with purulent discharge for ≥3 consecutive days). 1
• Confirm bacterial sinusitis using one of three criteria: persistent symptoms ≥10 days without improvement, severe symptoms for ≥3 consecutive days, or "double sickening" (worsening after initial improvement). 1

When to Refer to ENT Specialist

• Failure to respond to two courses of appropriate antibiotics 2, 3
• Recurrent sinusitis (≥3 episodes per year) requiring evaluation for underlying allergic rhinitis, immunodeficiency, or anatomic abnormalities 2, 3
• Suspected complications (orbital cellulitis, meningitis, intracranial involvement) 2, 3