What is the best antibiotic for an adult with a sinus infection that has persisted for about two weeks?

Best Antibiotic for Persistent Sinus Infection (2 Weeks)

For an adult with sinus symptoms persisting for 2 weeks, amoxicillin-clavulanate 875 mg/125 mg twice daily for 5–10 days is the first-line antibiotic, providing 90–92% predicted clinical efficacy against the three major sinusitis pathogens. 1

Confirm the Diagnosis First

Before prescribing antibiotics, verify that the patient meets criteria for acute bacterial rhinosinusitis rather than viral illness:

• 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 discharge, and facial pain 1, 2
• "Double sickening" – initial improvement from a viral URI followed by worsening within 10 days 1, 2

At 2 weeks, your patient meets the first criterion (persistent symptoms ≥10 days), making bacterial sinusitis likely. 1

Critical context: 98–99.5% of acute rhinosinusitis is viral and resolves spontaneously within 7–10 days without antibiotics. 1 The fact that symptoms have persisted for 2 weeks without improvement strongly suggests bacterial infection. 1

First-Line Antibiotic Regimen

Amoxicillin-clavulanate 875 mg/125 mg orally twice daily for 5–10 days is the guideline-recommended first-line agent. 1, 2 The clavulanate component is essential because 30–40% of Haemophilus influenzae and 90–100% of Moraxella catarrhalis produce β-lactamase, rendering plain amoxicillin ineffective. 1

This regimen provides 90–92% predicted clinical efficacy against the three major sinusitis pathogens: Streptococcus pneumoniae, H. influenzae, and M. catarrhalis. 1, 3

Treatment Duration

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

High-Dose Regimen for Specific Risk Factors

Use high-dose amoxicillin-clavulanate (2 g amoxicillin/125 mg clavulanate twice daily) if the patient has any of these risk factors: 1

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

Alternatives for Penicillin Allergy

Non-Severe (Non-Type I) Allergy

Second- or third-generation cephalosporins for 10 days are preferred because cross-reactivity with penicillin is negligible: 1

• Cefuroxime-axetil
• Cefpodoxime-proxetil
• Cefdinir
• Cefprozil

Severe (Type I/Anaphylactic) Allergy

Respiratory fluoroquinolones provide 90–92% predicted efficacy: 1, 4

• Levofloxacin 500 mg once daily for 10–14 days 1, 4
• Moxifloxacin 400 mg once daily for 10 days 1

These agents offer excellent coverage against multidrug-resistant S. pneumoniae and β-lactamase-producing organisms. 1, 4

Essential Adjunctive Therapies (Add to All Patients)

Intranasal corticosteroids (mometasone, fluticasone, or budesonide) twice daily significantly reduce mucosal inflammation and accelerate symptom resolution—supported by strong evidence from multiple randomized controlled trials. 1, 2

Additional supportive measures: 1, 2

• Saline nasal irrigation 2–3 times daily for symptomatic relief and mucus clearance
• Analgesics (acetaminophen or ibuprofen) for pain and fever control
• Decongestants (oral or topical); limit topical agents to ≤3 days to avoid rebound congestion

Monitoring and Reassessment

Reassess at 3–5 days: If no clinical improvement (persistent purulent drainage, unchanged facial pain, or worsening), switch immediately to high-dose amoxicillin-clavulanate or a respiratory fluoroquinolone. 1, 2

Reassess at 7 days: If symptoms persist or worsen, reconfirm the diagnosis, exclude complications (orbital cellulitis, meningitis, intracranial abscess), and consider imaging or ENT referral. 1, 2

Expected timeline: Most patients show noticeable improvement within 3–5 days of appropriate antibiotic therapy, with complete resolution by 10–14 days. 1, 2

Antibiotics to Avoid

Never use these as first-line therapy: 1

• Macrolides (azithromycin, clarithromycin) – 20–25% resistance rates in S. pneumoniae and H. influenzae
• Trimethoprim-sulfamethoxazole – 50% resistance in S. pneumoniae and 27% in H. influenzae
• First-generation cephalosporins (cephalexin) – inadequate coverage against H. influenzae because ~50% of strains produce β-lactamase
• Doxycycline – only 77–81% predicted efficacy with a 20–25% bacteriologic failure rate due to limited H. influenzae activity

Common Pitfalls

• Do not prescribe antibiotics based solely on purulent nasal discharge; this reflects neutrophilic inflammation common to viral disease. 1
• Gastrointestinal adverse effects with amoxicillin-clavulanate are common (diarrhea in 40–43% of patients; severe diarrhea in 7–8%). 1, 5, 6
• 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 prevent resistance development. 1

Referral to ENT

Refer immediately if: 1

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