What is the first‑line therapy for an otherwise healthy adult with acute bacterial sinusitis?

First-Line Therapy for Adult Sinus Infection

Amoxicillin-clavulanate 875 mg/125 mg twice daily for 5–10 days is the preferred first-line antibiotic for otherwise healthy adults with acute bacterial sinusitis, providing 90–92% predicted clinical efficacy against the major pathogens. 1

Confirm the Diagnosis Before Prescribing Antibiotics

Before initiating any antibiotic therapy, you must confirm that the patient meets criteria for acute bacterial rhinosinusitis (ABRS) rather than viral rhinosinusitis. 1, 2 The diagnosis requires at least one of three clinical patterns:

• Persistent symptoms ≥ 10 days without improvement: purulent nasal discharge plus either nasal obstruction/congestion or facial pain/pressure/fullness. 1, 2
• Severe symptoms ≥ 3–4 consecutive days at illness onset: fever ≥ 39°C (102.2°F) with purulent nasal discharge and facial pain. 1, 2
• "Double sickening": initial improvement from a viral upper respiratory infection followed by new-onset fever, worsening nasal discharge, or markedly increased cough within 10 days. 1, 2

Critical context: Approximately 98–99.5% of acute rhinosinusitis cases are viral and resolve spontaneously within 7–10 days without antibiotics. 1, 2 Do not prescribe antibiotics for symptoms lasting < 10 days unless the severe criteria above are met. 1, 2

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First-Line Antibiotic Regimen

Standard Regimen (No Recent Antibiotic Use)

• Amoxicillin-clavulanate 875 mg/125 mg orally twice daily for 5–10 days (or until symptom-free for 7 consecutive days, typically 10–14 days total). 1, 3
• This regimen is preferred over plain amoxicillin because 30–40% of Haemophilus influenzae and 90–100% of Moraxella catarrhalis produce β-lactamase, rendering plain amoxicillin ineffective against these organisms. 1
• Shorter 5–7 day courses provide comparable clinical efficacy with fewer adverse effects compared to traditional 10-day regimens. 1

High-Dose Regimen (Risk Factors for Resistant Organisms)

Use high-dose amoxicillin-clavulanate 2 g/125 mg twice daily when any of the following risk factors are present: 1, 2

• Recent antibiotic use within the past 4–6 weeks
• Age > 65 years
• Daycare exposure (patient or household contact)
• Moderate-to-severe symptoms
• Comorbidities (diabetes, chronic cardiac/hepatic/renal disease)
• Immunocompromised state

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Watchful Waiting as an Alternative

For adults with uncomplicated ABRS and reliable follow-up, initial observation without antibiotics is an appropriate strategy. 1, 2 Initiate antibiotics only if:

• No improvement by day 7, or
• Symptoms worsen at any time. 1, 2

Rationale: The number needed to treat (NNT) with antibiotics is 10–15 to achieve one additional cure compared with placebo, reflecting the high rate of spontaneous recovery. 1, 2

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Alternatives for Penicillin-Allergic Patients

Non-Severe (Non-Type I) Penicillin Allergy

• Second- or third-generation cephalosporins for 10 days: cefuroxime-axetil, cefpodoxime-proxetil, cefdinir, or cefprozil. 1, 3
• Cross-reactivity with penicillins is < 1%, making these agents safe in patients with mild rash or delayed reactions. 1

Severe (Type I/Anaphylactic) Penicillin Allergy

• Levofloxacin 500 mg once daily for 10–14 days 1, 4 or
• Moxifloxacin 400 mg once daily for 10 days. 1
• Both achieve 90–92% predicted efficacy against multidrug-resistant Streptococcus pneumoniae and β-lactamase-producing organisms. 1
• Reserve fluoroquinolones for severe penicillin allergy or documented treatment failure to limit resistance development. 1

Suboptimal Alternative (When Cephalosporins and Fluoroquinolones Contraindicated)

• Doxycycline 100 mg once daily for 10 days offers lower efficacy (77–81%) with a 20–25% bacteriologic failure rate due to limited H. influenzae coverage. 1
• Contraindicated in children < 8 years due to tooth enamel discoloration. 1

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Essential Adjunctive Therapies (Add to All Patients)

These therapies significantly improve outcomes and should be prescribed regardless of whether antibiotics are used:

• Intranasal corticosteroids (mometasone, fluticasone, or budesonide) twice daily markedly reduce mucosal inflammation and speed symptom resolution; supported by strong evidence from multiple randomized controlled trials. 1, 3
• Saline nasal irrigation 2–3 times daily provides symptomatic relief and enhances mucus clearance. 1, 3
• Analgesics (acetaminophen or ibuprofen) for pain and fever control. 1, 3
• Decongestants (oral or topical); limit topical use to ≤ 3 days to avoid rebound congestion. 1

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Monitoring and Reassessment

Early Reassessment (Days 3–5)

• If there is no clinical improvement (persistent purulent drainage, unchanged facial pain, or worsening), switch to high-dose amoxicillin-clavulanate 2 g/125 mg twice daily or a respiratory fluoroquinolone (levofloxacin or moxifloxacin). 1

Day 7 Reassessment

• Persistent or worsening symptoms require:
  1. Confirmation of ABRS diagnosis
  2. Exclusion of complications (orbital cellulitis, meningitis, intracranial abscess)
  3. Imaging (CT) only if complications are suspected
  4. Referral to otolaryngology when appropriate. 1

Expected Timeline of Recovery

• Noticeable improvement within 3–5 days of appropriate therapy. 1
• Complete resolution by 10–14 days or when symptom-free for 7 consecutive days. 1

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Antibiotics to Avoid

• Macrolides (azithromycin, clarithromycin): 20–25% resistance rates in S. pneumoniae and H. influenzae. 1
• Trimethoprim-sulfamethoxazole: ≈ 50% resistance in S. pneumoniae and ≈ 27% in H. influenzae. 1
• First-generation cephalosporins (e.g., cephalexin): inadequate because ≈ 50% of H. influenzae strains produce β-lactamase. 1

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Referral to Otolaryngology

Refer immediately for any of the following:

• No improvement after 7 days of appropriate second-line antibiotic therapy. 1
• Worsening symptoms at any point during treatment. 1
• Suspected complications: severe headache, visual changes, periorbital swelling/erythema, proptosis, diplopia, altered mental status, or cranial nerve deficits. 1
• Recurrent sinusitis (≥ 3 episodes per year) requiring evaluation for underlying allergic rhinitis, immunodeficiency, or anatomic abnormalities. 1

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Common Pitfalls to Avoid

• Do not prescribe antibiotics for symptoms < 10 days unless severe features (fever ≥ 39°C with purulent discharge for ≥ 3 consecutive days) are present. 1, 2
• Avoid routine imaging (X-ray or CT) for uncomplicated ABRS; up to 87% of viral upper-respiratory infections show sinus abnormalities on imaging, leading to unnecessary interventions. 1
• Ensure adequate treatment duration (≥ 5 days for adults) to prevent relapse. 1
• Fluoroquinolones should not be used as first-line therapy in patients without documented β-lactam allergy to limit resistance development. 1
• Gastrointestinal adverse effects with amoxicillin-clavulanate are common: diarrhea in 40–43% of patients and severe diarrhea in 7–8%. 1