In an adult with acute sinusitis for five days who has taken amoxicillin 875 mg twice daily for three days without improvement and has no penicillin allergy or significant comorbidities, what is the next step in management?

Switch to High-Dose Amoxicillin-Clavulanate or a Respiratory Fluoroquinolone

After 3 days of amoxicillin 875 mg twice daily without improvement, you should switch to high-dose amoxicillin-clavulanate (875 mg/125 mg twice daily) or a respiratory fluoroquinolone (levofloxacin 500 mg once daily or moxifloxacin 400 mg once daily) for 5-10 days. 1, 2, 3

Why the Initial Treatment Failed

Your patient likely has one of two problems:

• β-lactamase-producing organisms (Haemophilus influenzae or Moraxella catarrhalis) that are resistant to plain amoxicillin, with nearly 50% of H. influenzae strains producing β-lactamase 2, 4
• Drug-resistant Streptococcus pneumoniae (DRSP) that requires higher antibiotic concentrations 2, 4

Plain amoxicillin lacks the clavulanate component needed to overcome β-lactamase-producing bacteria, which explains the treatment failure 2, 4.

First-Line Second-Line Option: High-Dose Amoxicillin-Clavulanate

Switch to amoxicillin-clavulanate 875 mg/125 mg twice daily for 5-10 days as your preferred second-line agent 1, 2, 3. This provides:

• Coverage against β-lactamase-producing H. influenzae and M. catarrhalis 2, 4
• Enhanced activity against penicillin-resistant S. pneumoniae 2, 4
• 90-92% predicted clinical efficacy against all major sinusitis pathogens 2, 3

The clavulanate component specifically inhibits β-lactamase enzymes, restoring amoxicillin's effectiveness 2, 4.

Alternative Second-Line Option: Respiratory Fluoroquinolones

If the patient cannot tolerate amoxicillin-clavulanate (common GI side effects include diarrhea in 40-43% of patients) 5, switch to levofloxacin 500 mg once daily or moxifloxacin 400 mg once daily for 10 days 2, 3. These provide:

• 90-92% predicted clinical efficacy against resistant pathogens 2, 3
• Excellent coverage against multi-drug resistant S. pneumoniae (MDRSP) 2
• Complete coverage of β-lactamase-producing organisms 2, 3

However, reserve fluoroquinolones to prevent resistance development—they should not be routine first-line therapy 1, 2.

Critical Reassessment Timeline

Reassess at 3-5 days after switching antibiotics 1, 2, 3:

• If no improvement → consider imaging (CT scan) to exclude complications or alternative diagnosis 1, 2
• If worsening at any time → immediately evaluate for complications (orbital cellulitis, meningitis, brain abscess) and refer to ENT 1, 2

By day 7 of the new antibiotic, most patients should show significant improvement 2. If symptoms persist or worsen at 7 days, reconfirm the diagnosis and consider referral to otolaryngology 1, 2.

Essential Adjunctive Therapies

Add these to enhance outcomes regardless of antibiotic choice:

• Intranasal corticosteroids (mometasone, fluticasone, or budesonide twice daily) to reduce mucosal inflammation 1, 2, 3
• Saline nasal irrigation for symptomatic relief and improved drainage 1, 2, 3
• Analgesics (acetaminophen or ibuprofen) for pain and fever 2
• Adequate hydration and sleeping with head elevated 2

These adjunctive measures have strong evidence from multiple RCTs showing improved symptom resolution 1, 2.

Common Pitfall: Continuing Ineffective Therapy

Do not continue amoxicillin beyond 3-5 days without improvement 1, 2. The 3-5 day reassessment point is specifically designed to catch early treatment failures and prevent complications 1, 2. Waiting beyond this timepoint delays effective treatment and may allow bacterial proliferation 2.

Treatment Duration

Continue the new antibiotic for 5-10 days total, or until symptom-free for 7 consecutive days (typically 10-14 days total) 1, 2, 3. Recent evidence supports shorter 5-7 day courses with comparable efficacy and fewer adverse effects 2, 6.

When to Refer

Refer to ENT if:

• No improvement after 7 days of appropriate second-line therapy 1, 2, 3
• Worsening symptoms at any time 1, 2
• Suspected complications (severe headache, visual changes, altered mental status, periorbital swelling) 1, 2
• Recurrent sinusitis (≥3 episodes per year) requiring evaluation for underlying allergic rhinitis, immunodeficiency, or anatomic abnormalities 1, 2