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

Best Antibiotic for a Sinus Infection

Amoxicillin-clavulanate 875 mg/125 mg twice daily for 5-10 days is the best first-line antibiotic for an otherwise healthy adult with acute bacterial sinusitis. 1, 2, 3

Confirm the Diagnosis First

Before prescribing any antibiotic, verify that the patient meets at least one of these three criteria for acute bacterial rhinosinusitis (ABRS), because 98-99.5% of acute sinus infections are viral and resolve without antibiotics within 7-10 days 1, 2:

• Persistent symptoms ≥10 days without improvement (purulent nasal discharge plus nasal obstruction or facial pain/pressure) 1, 2
• Severe symptoms ≥3-4 consecutive days with fever ≥39°C, purulent nasal discharge, and facial pain 1, 2
• "Double sickening" – worsening after initial improvement from a viral upper respiratory infection 1, 2

Do not prescribe antibiotics for symptoms lasting less than 10 days unless severe features are present. 1, 2

Why Amoxicillin-Clavulanate Is First-Line

Amoxicillin-clavulanate achieves 90-92% predicted clinical efficacy against the three major bacterial pathogens causing sinusitis: Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis 1, 2, 4. The clavulanate component is critical because approximately 30-40% of H. influenzae and 90-100% of M. catarrhalis strains produce β-lactamase enzymes that inactivate plain amoxicillin 1, 2.

Plain amoxicillin alone (without clavulanate) is acceptable only for mild disease in patients who have not received antibiotics in the past 4-6 weeks, but amoxicillin-clavulanate is preferred in most cases 1, 3.

Treatment Duration

• Standard duration: 5-10 days, or continue until symptom-free for 7 consecutive days (typically 10-14 days total) 1, 2, 3
• Shorter 5-7 day courses provide comparable efficacy with fewer adverse effects and are increasingly recommended 1, 2, 3

When to Use High-Dose Amoxicillin-Clavulanate

Switch to high-dose amoxicillin-clavulanate (2 g amoxicillin/125 mg clavulanate twice daily) if the patient has any of these risk factors for resistant organisms 1, 2:

• Recent antibiotic use within the past 4-6 weeks 1
• Age >65 years 1, 5
• Moderate-to-severe symptoms 1
• Comorbid conditions (diabetes, chronic cardiac/hepatic/renal disease) 1
• Immunocompromised state 1
• Close contact with daycare children 1
• Smoking or exposure to smokers 1

Alternatives for Penicillin Allergy

Non-Severe (Non-Type I) Penicillin Allergy

Use a second- or third-generation cephalosporin for 10 days – cross-reactivity is negligible 1, 2, 3:

• Cefuroxime-axetil 1, 2
• Cefpodoxime-proxetil 1, 2
• Cefdinir 1, 2
• Cefprozil 1, 2

Severe (Type I/Anaphylactic) Penicillin Allergy

Use a respiratory fluoroquinolone 1, 2, 3:

• Levofloxacin 500 mg once daily for 10-14 days (90-92% predicted efficacy) 1, 2, 4
• Moxifloxacin 400 mg once daily for 10 days (90-92% predicted efficacy) 1, 2, 4

Doxycycline 100 mg once daily for 10 days is an acceptable but suboptimal alternative (77-81% predicted efficacy, with 20-25% bacteriologic failure rate) 1, 2, 3.

Essential Adjunctive Therapies (Add to All Patients)

These improve outcomes regardless of antibiotic choice:

• Intranasal corticosteroids (mometasone, fluticasone, or budesonide) twice daily – reduces mucosal inflammation and accelerates symptom resolution (strong evidence from multiple RCTs) 1, 2
• Saline nasal irrigation 2-3 times daily – provides symptomatic relief and clears mucus 1, 2
• Analgesics (acetaminophen or ibuprofen) – for pain and fever control 1, 2

Monitoring and Reassessment

• Reassess at 3-5 days: If no improvement, switch to high-dose amoxicillin-clavulanate or a respiratory fluoroquinolone 1, 2, 3
• Reassess at 7 days: If symptoms persist or worsen, reconfirm the diagnosis, exclude complications (orbital cellulitis, meningitis), and consider imaging or ENT referral 1, 2

Antibiotics to Avoid

• Azithromycin and other macrolides – 20-25% resistance rates for S. pneumoniae and H. influenzae make them unsuitable 1, 2
• Trimethoprim-sulfamethoxazole – 50% resistance in S. pneumoniae and 27% in H. influenzae 1, 2
• First-generation cephalosporins (cephalexin) – inadequate coverage against H. influenzae (50% produce β-lactamase) 1, 2

Watchful Waiting Option

For uncomplicated cases with reliable follow-up, initial observation without antibiotics is appropriate. Start antibiotics only if there is no improvement by day 7 or if symptoms worsen at any time 1, 2, 3. The number needed to treat with antibiotics is 10-15 to achieve one additional cure, reflecting the high rate of spontaneous recovery 1, 2.

Common Pitfalls

• Gastrointestinal adverse effects are common with amoxicillin-clavulanate – diarrhea occurs in 40-43% of patients (severe in 7-8%) 1, 6, 7
• Do not use fluoroquinolones as first-line therapy in patients without documented β-lactam allergy – reserve them to prevent resistance development 1, 2, 3
• Ensure adequate treatment duration (minimum 5 days for adults) to prevent relapse 1, 2

When to Refer to ENT

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