What antibiotic is recommended for a patient with an Upper Respiratory Infection (URI) that is not improving?

Antibiotic Treatment for Non-Resolving Upper Respiratory Infection

For a URI not improving after 10 days, amoxicillin-clavulanate 875/125 mg twice daily is the first-line antibiotic choice, as symptom persistence beyond 10 days strongly indicates acute bacterial rhinosinusitis rather than viral infection. 1

Critical Diagnostic Clarification

Most URIs are viral and require only supportive care—antibiotics cause more harm than benefit in these cases. 1 However, three specific clinical scenarios warrant antibiotic therapy:

• Symptoms persisting ≥10 days without improvement (your scenario) 1
• Severe symptoms: fever >39°C with purulent nasal discharge or facial pain for ≥3 consecutive days 1
• "Double sickening": initial improvement followed by worsening after a typical viral URI 1

Common pitfall: Prescribing antibiotics for viral URIs before 10 days. The watchful waiting window is 7-10 days; only after this period does bacterial sinusitis become the likely diagnosis. 1

Recommended Antibiotic Regimen

First-Line Treatment

• Amoxicillin-clavulanate 875/125 mg twice daily for adults 2, 1, 3
• Amoxicillin-clavulanate 90 mg/kg/day (divided twice daily) for children, maximum 4 g/day 2, 3
• Duration: 7-10 days for sinusitis 1
• Take at the start of meals to minimize GI intolerance and enhance clavulanate absorption 3

Rationale: Amoxicillin-clavulanate provides coverage against the three most common bacterial pathogens: penicillin-resistant Streptococcus pneumoniae, β-lactamase-producing Haemophilus influenzae, and Moraxella catarrhalis. 2, 1, 4

Alternative Options (if amoxicillin-clavulanate contraindicated)

For penicillin allergy (non-Type I hypersensitivity/rash only):

• Second-generation cephalosporins: cefuroxime-axetil 2, 1
• Third-generation cephalosporins: cefpodoxime-proxetil or cefotiam-hexetil (NOT cefixime) 2, 1

For true β-lactam allergy (Type I hypersensitivity):

• Respiratory fluoroquinolones: levofloxacin or moxifloxacin 2, 1
• Doxycycline 1

Critical caveat: Macrolides (azithromycin, clarithromycin) and TMP-SMX have 20-25% bacterial failure rates due to high pneumococcal resistance and should be avoided unless the patient has true β-lactam allergy. 2

Risk Factors Requiring Higher Dosing

Use higher amoxicillin doses (4 g/day in adults, 90 mg/kg/day in children) if any of these apply:

• Antibiotic use within the past 4-6 weeks 2
• Age <2 years or daycare attendance 2
• Moderate-to-severe symptoms 2
• Geographic areas with high penicillin-resistant S. pneumoniae prevalence 2

Monitoring and Reassessment

• Assess response after 48-72 hours 2, 1
• Primary indicator: fever resolution (typically within 24 hours for pneumococcal infections, 2-4 days for other bacteria) 1
• Cough may persist longer and should not be the sole indicator of treatment failure 1

If no improvement after 72 hours:

• Reevaluate clinically and consider imaging (CT scan) 2
• Consider switching to respiratory fluoroquinolone 2
• Consider hospitalization if complications suspected 1

Adjunctive Supportive Measures

Combine antibiotics with:

• Intranasal saline irrigation to improve symptom relief 1
• Intranasal corticosteroids for enhanced outcomes 1
• Analgesics/antipyretics for facial pain and fever 1

What NOT to Prescribe

• First-generation cephalosporins (cephalexin): inadequate activity against penicillin-resistant S. pneumoniae 1
• Cefixime: explicitly not recommended 1
• Macrolides as first-line: high resistance rates (56% pneumococcal resistance) 2
• Fluoroquinolones inactive against pneumococci (ciprofloxacin, ofloxacin) 1