In an adult with acute bacterial sinusitis who has not improved after a 5‑7‑day course of amoxicillin‑clavulanate (500 mg/125 mg three times daily), what is the next appropriate management?

Management of Acute Bacterial Sinusitis Refractory to Amoxicillin-Clavulanate

Switch immediately to a respiratory fluoroquinolone—either levofloxacin 500 mg once daily or moxifloxacin 400 mg once daily for 5–10 days—because these agents achieve 90–92% predicted clinical efficacy against resistant pathogens including penicillin-resistant Streptococcus pneumoniae and β-lactamase-producing Haemophilus influenzae. 1

Why Amoxicillin-Clavulanate Fails

When a patient does not improve after 5–7 days of amoxicillin-clavulanate, the most likely explanations are:

• Drug-resistant S. pneumoniae (DRSP) that has developed resistance mechanisms beyond what clavulanate can overcome 2
• Recent antibiotic exposure (within the past 4–6 weeks) creates a major risk factor for harboring resistant organisms, necessitating a different antibiotic class 1
• Inadequate tissue penetration in patients with severe mucosal edema or anatomic obstruction 2

The 5–7 day timeframe is critical: if no improvement occurs by day 3–5, you are dealing with treatment failure and must switch antibiotics immediately rather than extending the ineffective regimen. 3, 2

First-Line Alternative: Respiratory Fluoroquinolones

Levofloxacin 500 mg once daily for 10–14 days is the preferred next step because:

• 90–92% predicted clinical efficacy against all major sinusitis pathogens 1, 4
• Excellent coverage of multidrug-resistant S. pneumoniae including strains resistant to penicillin, macrolides, and trimethoprim-sulfamethoxazole 2, 4
• Complete activity against β-lactamase-producing organisms (H. influenzae and M. catarrhalis) 1, 5
• Once-daily dosing improves compliance compared to twice- or thrice-daily regimens 5

Moxifloxacin 400 mg once daily for 5–10 days is equally effective:

• 99% activity against S. pneumoniae and 95–100% activity against H. influenzae 1
• Shorter course option (5–7 days) with comparable efficacy to 10-day regimens 6, 7
• Similar tolerability profile to levofloxacin with drug-related adverse events in approximately 7–32% of patients (primarily nausea, diarrhea) 7, 5

The choice between levofloxacin and moxifloxacin is largely institutional preference; both achieve equivalent clinical and bacteriologic success rates of 88–93% in head-to-head comparisons. 7, 5

Second-Line Alternatives (When Fluoroquinolones Cannot Be Used)

If fluoroquinolones are contraindicated or refused:

• High-dose amoxicillin-clavulanate (2 g/125 mg twice daily) for 10–14 days provides enhanced coverage against DRSP, though this approach has limited evidence after standard-dose failure 2, 8
• Third-generation cephalosporins (cefpodoxime, cefdinir) for 10 days offer superior activity against H. influenzae but have limitations against DRSP 2, 1
• Parenteral ceftriaxone 1–2 g IM or IV daily for 5 days ensures adequate tissue concentrations and achieves 90–92% predicted efficacy, particularly useful when oral compliance is uncertain 2, 1

Important caveat: A recent randomized trial found no benefit of high-dose over standard-dose amoxicillin-clavulanate in adults with acute sinusitis, with similar efficacy (44.3% vs 36.4% reporting "a lot better" or "no symptoms" at day 3) and comparable rates of severe diarrhea (7.0% vs 7.7%). 8 This suggests that simply increasing the amoxicillin dose after standard-dose failure is unlikely to succeed—switching antibiotic classes is more rational.

Essential Adjunctive Therapies (Add to All Patients)

These interventions enhance treatment success regardless of antibiotic choice:

• Intranasal corticosteroids (mometasone, fluticasone, or budesonide) twice daily reduce mucosal inflammation and improve symptom resolution; particularly beneficial when marked mucosal edema or nasal polyposis is present 2, 1, 9
• High-volume saline nasal irrigation 2–3 times daily provides symptomatic relief and enhances sinus drainage 2, 1
• Analgesics (acetaminophen or ibuprofen) for pain and fever control 2, 1
• Adequate hydration and warm facial packs to improve mucus clearance 1

Multiple randomized controlled trials provide strong evidence that combining intranasal corticosteroids with antibiotics accelerates symptom resolution compared to antibiotics alone. 2

Monitoring Response to New Therapy

Reassess at 3–5 days after switching antibiotics:

• If symptoms worsen after 48–72 hours or fail to improve after 3–5 days, further evaluation is needed 1
• Consider obtaining cultures by direct sinus aspiration or endoscopically guided cultures if the patient fails second-line therapy 1
• Evaluate urgently for complications (orbital cellulitis, meningitis, intracranial abscess) if severe headache, visual changes, periorbital swelling, or altered mental status develop 2

Reassess at 7 days:

• If symptoms persist or worsen, reconfirm the diagnosis and exclude alternative causes (fungal sinusitis, anatomic obstruction, immunodeficiency) 3, 2
• Consider CT imaging only when complications are suspected or an alternative diagnosis is likely—routine imaging is not recommended 2

When to Refer to Otolaryngology

Refer immediately if any of the following occur:

• No improvement after 7 days of appropriate second-line fluoroquinolone therapy 2, 1
• Worsening symptoms at any point during treatment 2, 1
• Suspected complications (orbital cellulitis, meningitis, intracranial abscess) 2
• Recurrent sinusitis (≥3 episodes per year) requiring evaluation for underlying allergic rhinitis, immunodeficiency, or anatomic abnormalities 2, 10

Critical Pitfalls to Avoid

• Do not simply extend the amoxicillin-clavulanate course beyond 7 days without clinical improvement—this delays effective treatment and allows complications to develop 2
• Do not switch to azithromycin or other macrolides due to 20–25% resistance rates among S. pneumoniae and H. influenzae 2
• Do not use trimethoprim-sulfamethoxazole due to 50% resistance in S. pneumoniae and 27% resistance in H. influenzae 2
• Do not use first-generation cephalosporins (cephalexin) due to inadequate coverage of H. influenzae (≈50% produce β-lactamase) 2
• Ensure adequate treatment duration (minimum 5 days for adults, 10 days for children) to prevent relapse 3, 2

Treatment Duration and Completion

Continue the fluoroquinolone for:

• 5–10 days total for uncomplicated cases 1, 6, 7
• Until symptom-free for 7 consecutive days (typically 10–14 days overall) 2, 10

Recent evidence supports shorter 5–7 day courses with comparable efficacy and fewer adverse effects compared to traditional 10-day regimens. 6, 7