What first‑line antibiotics are recommended for an adult COPD exacerbation with increased dyspnea and sputum purulence or volume, including options for penicillin allergy, Pseudomonas risk, and severe hospitalized cases?

Antibiotic Selection for COPD Exacerbation

For adults with COPD exacerbation meeting antibiotic criteria, prescribe amoxicillin-clavulanate 875/125 mg orally twice daily for 5-7 days as first-line therapy when Pseudomonas risk factors are absent. 1, 2, 3

When to Prescribe Antibiotics

Antibiotics are indicated only when specific clinical criteria are met:

• Type I Anthonisen exacerbation: All three cardinal symptoms present—increased dyspnea, increased sputum volume, AND increased sputum purulence 1, 2
• Type II Anthonisen exacerbation with purulence: Two cardinal symptoms present when purulent sputum is one of them 1, 2
• Severe exacerbation requiring mechanical ventilation (invasive or non-invasive) 1, 4

Do NOT prescribe antibiotics for Type II exacerbations without purulence or Type III exacerbations (≤1 cardinal symptom) unless mechanical ventilation is required 1, 3

When appropriately prescribed, antibiotics reduce short-term mortality by 77% and treatment failure by 53% 2

First-Line Antibiotic Options (No Pseudomonas Risk)

Standard Regimen

Amoxicillin-clavulanate 875/125 mg orally twice daily for 5-7 days 1, 2, 3, 4

• The clavulanate component neutralizes β-lactamase production present in 20-30% of Haemophilus influenzae isolates 2
• The higher dose achieves bronchial concentrations sufficient to overcome penicillin-resistant Streptococcus pneumoniae 2
• Never use plain amoxicillin—it is associated with higher relapse rates and fails against β-lactamase-producing organisms 2

Alternative Options

Respiratory fluoroquinolones are acceptable alternatives:

• Levofloxacin 500 mg orally once daily for 5-7 days 1, 2, 3
• Moxifloxacin 400 mg orally once daily for 5 days 1, 2, 3

Both achieve bronchial concentrations several-fold above the MIC for typical COPD pathogens 2

Doxycycline 100 mg orally twice daily for 5-7 days is an acceptable alternative 3

Penicillin Allergy Options

For patients with penicillin allergy and no Pseudomonas risk:

• Levofloxacin 500 mg orally once daily for 5-7 days 1, 2
• Moxifloxacin 400 mg orally once daily for 5 days 1, 2
• Doxycycline 100 mg orally twice daily for 5-7 days 3

Avoid macrolides (including azithromycin)—they have high S. pneumoniae resistance rates (30-50% in some regions) and most H. influenzae isolates are resistant to clarithromycin 2

Pseudomonas Risk Assessment

Pseudomonas coverage is required when ≥2 of the following are present:

1. Recent hospitalization 1
2. Frequent antibiotic use (>4 courses per year OR any use within last 3 months) 1
3. Severe COPD (FEV₁ <30% predicted) 1
4. Oral corticosteroid use (>10 mg prednisolone daily in last 2 weeks) 1
5. Prior isolation or colonization with P. aeruginosa 1

Antibiotic Selection for Pseudomonas Risk

Oral Regimen

Ciprofloxacin 750 mg orally twice daily for 7-10 days 1, 2, 4

• High-dose ciprofloxacin is required to reach therapeutic bronchial concentrations 2
• Alternative: Levofloxacin 750 mg orally once daily 1, 2

Parenteral Regimen (Severe/Hospitalized Cases)

When IV therapy is needed:

• Ciprofloxacin IV OR β-lactam with anti-pseudomonal activity (e.g., cefepime, piperacillin-tazobactam, carbapenem) 1
• Addition of aminoglycosides is optional 1

Route of Administration

• Prefer oral route when the patient can tolerate oral intake 1, 2
• Use IV route for patients unable to eat, severe illness, or ICU admission 1, 2
• Switch from IV to oral by day 3 if clinically stable 1, 2

Microbiological Testing

Obtain sputum culture or endotracheal aspirate before starting antibiotics in any of these situations:

• Severe exacerbation requiring hospitalization 1, 2, 3
• Suspected Pseudomonas infection 2, 3
• Prior antibiotic or oral steroid treatment 1, 2
• Prolonged disease course 2

• 4 exacerbations per year 1, 2

• FEV₁ <30% predicted 1, 2, 3

Treatment Duration

• Standard duration: 5-7 days for most exacerbations 2, 3, 4
• 7-10 days for Pseudomonas coverage 1, 2
• Shorter fluoroquinolone courses (5 days) are as effective as longer β-lactam courses 2
• Do not extend beyond 7 days for a single exacerbation unless culture results dictate otherwise 2

Management of Treatment Failure

If no clinical improvement within 48-72 hours:

1. Re-evaluate for non-infectious causes: cardiac failure, pulmonary embolism, pneumothorax, inadequate bronchodilator therapy 1, 2
2. Obtain sputum culture promptly 1, 2
3. Escalate antibiotic coverage to include P. aeruginosa, resistant S. pneumoniae, and non-fermenting Gram-negatives 1, 2, 4
4. Consider adding ciprofloxacin (if not already used) or a β-lactam with anti-pseudomonal activity 2

Adjunctive Therapy

Always combine antibiotics with:

• Systemic corticosteroids: Prednisone 40 mg orally daily for 5 days—reduces treatment failure by >50% and improves lung function 2, 3
• Short-acting bronchodilators: β₂-agonists with or without anticholinergics 2, 3

Common Pitfalls to Avoid

• Never use plain amoxicillin—higher relapse rates and β-lactamase resistance 2
• Avoid macrolides for acute exacerbations—high resistance rates render them ineffective 2
• Do not use doxycycline in patients with Pseudomonas risk factors 3
• Do not prescribe antibiotics for Type III exacerbations unless mechanical ventilation is required 1, 2