What first‑line oral antibiotic regimen is recommended for an adult with an acute COPD exacerbation who meets criteria for antibiotic therapy (increased dyspnea, increased sputum volume and purulence, or need for systemic steroids), and what alternatives should be considered for penicillin allergy or risk factors for resistant organisms?

Antibiotic Selection for COPD Exacerbation

First-Line Oral Antibiotic Regimen

Amoxicillin-clavulanate 875/125 mg orally twice daily for 5–7 days is the recommended first-line antibiotic for adults with acute COPD exacerbation who meet criteria for antibiotic therapy and have no risk factors for Pseudomonas aeruginosa. 1, 2

When to Prescribe Antibiotics

Antibiotics are indicated when patients present with:

• All three cardinal symptoms (Anthonisen Type I): increased dyspnea, increased sputum volume, AND increased sputum purulence 1, 3
• Two cardinal symptoms (Anthonisen Type II) when purulent sputum is one of them 1, 3
• Severe exacerbation requiring mechanical ventilation (invasive or noninvasive) 1, 3

Antibiotics reduce short-term mortality by 77%, treatment failure by 53%, and hospitalization duration when appropriately indicated. 1, 3

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Alternative First-Line Options for Standard-Risk Patients

Respiratory Fluoroquinolones

• Levofloxacin 500 mg orally once daily for 5–7 days 2
• Moxifloxacin 400 mg orally once daily for 5 days 2, 4

Both agents achieve bronchial-secretion concentrations several-fold above the minimum inhibitory concentration for typical COPD pathogens (Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis). 2 Moxifloxacin offers once-daily dosing, which improves compliance. 2

Tetracycline

• Doxycycline is an acceptable alternative first-line option with reasonable activity against usual COPD pathogens. 2, 5

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Penicillin Allergy Management

For patients with penicillin allergy, use a respiratory fluoroquinolone (levofloxacin 500 mg daily or moxifloxacin 400 mg daily for 5 days) as the preferred alternative. 2

Doxycycline may also be considered, though fluoroquinolones provide broader and more reliable coverage. 2, 5

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Risk Stratification for Pseudomonas aeruginosa

Identifying High-Risk Patients

Pseudomonas coverage is required when at least two of the following risk factors are present: 1, 2, 3

1. Recent hospitalization 1, 2
2. Frequent antibiotic use (>4 courses per year) or recent antibiotic use (within last 3 months) 1, 2
3. Severe COPD (FEV₁ <30% predicted) 1, 2
4. Previous isolation of P. aeruginosa or known colonization 1, 2

Antibiotic Selection for Pseudomonas Risk

Ciprofloxacin 750 mg orally twice daily for 7–10 days is the preferred agent when Pseudomonas risk is present. 1, 2

• Alternative: Levofloxacin 750 mg orally once daily (though clinical experience is more limited) 2
• High-dose ciprofloxacin is required to reach therapeutic serum and bronchial concentrations. 2

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Antibiotics to Avoid

Plain Amoxicillin

Do not use plain amoxicillin because it is associated with higher relapse rates and fails to cover β-lactamase-producing H. influenzae (present in 20–30% of strains). 2, 5

Macrolides

Macrolides (including azithromycin and clarithromycin) are generally not recommended for acute COPD exacerbations due to high S. pneumoniae resistance rates (30–50% in some European regions) and H. influenzae resistance to clarithromycin. 2, 5 When macrolides appear effective, the benefit likely relates to anti-inflammatory properties rather than antimicrobial activity. 2

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Duration and Route of Administration

Standard Duration

The recommended duration of antibiotic therapy is 5–7 days. 1, 2, 3

Shorter 5-day courses with fluoroquinolones may be as effective as 10-day β-lactam courses. 2

Route Selection

• Prefer the oral route when the patient can tolerate oral intake. 1, 2
• Use intravenous therapy for patients unable to eat, those with severe illness, or those admitted to intensive care. 1, 2
• Switch from IV to oral by day 3 if the patient is clinically stable. 1, 2

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Microbiological Testing

Obtain sputum culture or endotracheal aspirate before initiating antibiotics in the following situations: 1, 2, 3

• Severe exacerbation requiring hospitalization 1, 2
• Suspected Pseudomonas infection 1, 2
• Prior antibiotic or oral steroid treatment 1, 2
• Prolonged disease course 1, 2
• More than 4 exacerbations per year 1, 2
• FEV₁ <30% predicted 1, 2

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Management of Treatment Failure

If no clinical improvement occurs within 48–72 hours:

1. Reassess for non-infectious causes (cardiac failure, pulmonary embolism, pneumonia) 1, 3
2. Obtain sputum culture promptly 1, 2
3. Escalate to an antibiotic with broader activity against P. aeruginosa, resistant S. pneumoniae, and non-fermenting Gram-negatives 2, 3
4. Consider adding ciprofloxacin (if not already used) or a β-lactam with anti-pseudomonal activity 1, 2

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Common Pitfalls to Avoid

• Do not prescribe antibiotics for Type III Anthonisen exacerbations (one or none of the cardinal symptoms) unless mechanical ventilation is required. 1
• Do not use plain amoxicillin due to β-lactamase resistance. 2, 5
• Do not rely on macrolides as monotherapy given high resistance rates. 2, 5
• Do not continue antibiotics beyond 7 days for a single exacerbation unless cultures dictate otherwise. 1, 2

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Adjunctive Therapy

Always combine antibiotics with:

• Systemic corticosteroids: Prednisone 40 mg orally daily for 5 days 1, 2, 5
• Short-acting bronchodilators: β₂-agonists with or without anticholinergics 1, 5

Systemic corticosteroids improve lung function, oxygenation, shorten recovery time, and reduce treatment failure by over 50%. 1, 5