What is the antibiotic of choice for bacterial upper respiratory infection (URI) with cough?

Antibiotic Treatment for Bacterial Upper Respiratory Tract Infections with Cough

Most upper respiratory tract infections with cough are viral and should not be treated with antibiotics, as they cause more harm than benefit; however, if bacterial infection is confirmed or strongly suspected based on specific clinical criteria, amoxicillin-clavulanate is the first-line antibiotic of choice. 1

Critical Initial Assessment: Viral vs. Bacterial

The vast majority of URTIs with cough are viral and require only supportive care. 2, 3 The key clinical distinction is whether the infection occurs above the vocal cords (true URTI) with normal pulmonary auscultation, or represents lower respiratory tract involvement. 4

When Antibiotics Are NOT Indicated

• Common cold, influenza, COVID-19, laryngitis, and uncomplicated acute bronchitis should never receive antibiotics, even with fever present. 2
• Acute bronchiolitis and simple bronchitis are 90% viral in origin and antibiotics provide no benefit. 4
• In otherwise healthy adults with acute bronchitis, no antibiotics are needed regardless of fever. 5

When to Consider Bacterial Infection

Antibiotics should only be initiated when specific clinical criteria suggest bacterial etiology:

• Symptoms persisting beyond 10 days without improvement strongly suggest acute bacterial rhinosinusitis rather than viral infection. 1
• Severe symptoms: fever >39°C with purulent nasal discharge or facial pain for ≥3 consecutive days. 1
• "Double sickening" pattern: worsening after initial improvement following a typical viral URI. 1
• For acute bronchitis, fever >38.5°C persisting for more than 3 days may warrant antibiotic consideration. 4, 5

First-Line Antibiotic Choice

Amoxicillin-Clavulanate as Preferred Agent

When bacterial URTI is confirmed, amoxicillin-clavulanate is the first-line treatment because it provides coverage against the most common pathogens including penicillin-resistant Streptococcus pneumoniae, beta-lactamase-producing Haemophilus influenzae, and Moraxella catarrhalis. 1, 6

• For bacterial rhinosinusitis, amoxicillin-clavulanate is the preferred agent when antibiotics are deemed necessary. 1
• The FDA approves amoxicillin-clavulanate specifically for sinusitis and lower respiratory tract infections caused by beta-lactamase-producing isolates of H. influenzae and M. catarrhalis. 6
• This combination has demonstrated high bacteriological and clinical efficacy in respiratory tract infections over 20 years, with tissue concentrations well above MIC90 for common respiratory pathogens. 7, 8

Alternative Options for Beta-Lactam Allergies

• Doxycycline is an appropriate alternative if amoxicillin-clavulanate is contraindicated. 1, 9
• Respiratory fluoroquinolones (levofloxacin or moxifloxacin) are another alternative option. 1, 10
• Macrolides, pristinamycin, or doxycycline may be used for patients with beta-lactam allergies. 5

Agents to AVOID

First-generation cephalosporins (such as cephalexin), ciprofloxacin, cefixime, trimethoprim-sulfamethoxazole, and tetracyclines should NOT be used due to inadequate activity against penicillin-resistant S. pneumoniae. 4, 1, 5

Treatment Duration and Monitoring

• For sinusitis, standard treatment duration is 7-10 days, though 5-day courses with certain second/third-generation cephalosporins have shown efficacy. 1
• For bronchitis exacerbations requiring antibiotics, treatment duration should be 5-8 days. 5
• Therapeutic efficacy must be assessed after 2-3 days of treatment. 1, 5
• Fever should resolve within 24 hours for pneumococcal infections and 2-4 days for other bacterial etiologies. 1
• Treatment should not be changed within the first 72 hours unless the patient's clinical condition worsens. 4, 5
• Cough may persist longer and should not be used as the sole indicator of treatment failure. 1

Adjunctive Supportive Measures

Even when antibiotics are indicated, combine with supportive therapies:

• Intranasal saline irrigation to improve symptom relief and potentially reduce antibiotic duration. 1
• Intranasal corticosteroids may enhance outcomes. 1
• Analgesics and antipyretics for facial pain and fever management. 1

Common Pitfalls to Avoid

• Do not treat all URTIs with antibiotics despite most being viral in origin—this is the most common error. 5, 2
• Do not use fluoroquinolones as first-line therapy when narrower-spectrum antibiotics would be appropriate. 5
• Do not assume all cephalosporins are equivalent—second and third-generation agents have significantly better activity against respiratory pathogens than first-generation drugs. 1
• When susceptibility testing shows susceptibility to amoxicillin alone (no beta-lactamase production), amoxicillin-clavulanate should not be used; plain amoxicillin is sufficient. 6