What are the indications, contraindications, and recommended antibiotic regimens for managing bronchiectasis?

Antibiotic Management in Bronchiectasis

Indications for Antibiotic Therapy

Long-term antibiotic prophylaxis should be offered to adults with bronchiectasis who experience three or more exacerbations per year, but only after optimizing airway clearance techniques and treating modifiable underlying causes. 1, 2

Acute Exacerbations

• Treat all acute exacerbations with antibiotics for 14 days, selecting agents based on prior sputum microbiology and risk factors for Pseudomonas aeruginosa infection 1, 3
• Collect sputum for culture and sensitivity before starting antibiotics, particularly in hospitalized patients, then initiate empirical therapy immediately without waiting for results 3
• Modify antibiotic selection if no clinical improvement occurs, guided by culture sensitivity results 3

Long-Term Prophylactic Therapy (≥3 Exacerbations/Year)

• For chronic P. aeruginosa infection: Inhaled colistin is first-line long-term therapy 1, 4, 2
• For non-Pseudomonas infections: Oral macrolides (azithromycin or erythromycin) are first-line 1, 2
• Inhaled gentamicin serves as second-line for P. aeruginosa when colistin is not tolerated 4
• Macrolides can be added to or substituted for inhaled antibiotics in patients with persistent high exacerbation frequency despite inhaled therapy 1

Eradication Therapy

• First isolation of P. aeruginosa: Offer eradication treatment immediately with oral ciprofloxacin 500-750 mg twice daily for 2 weeks as first-line 3, 4
• Alternative eradication regimens include intravenous antibiotics (beta-lactam plus aminoglycoside) for 2 weeks, or combination therapy with oral/IV antibiotics plus inhaled antibiotics (colistin/tobramycin) continued for 3 months total duration 1
• Evidence suggests regimens including nebulized antibiotics achieve greater clearance rates (80% initial, 54% sustained) and reduce exacerbation frequency from 3.93 to 2.09 per year 1
• New MRSA isolation with clinical deterioration: Offer eradication with oral doxycycline 100 mg twice daily for 14 days 3

Specific Antibiotic Regimens

For Patients WITHOUT Pseudomonas aeruginosa Risk

• Empirical first-line: Amoxicillin-clavulanate 625 mg three times daily for 14 days, covering H. influenzae, M. catarrhalis, and S. pneumoniae 3
• Pathogen-directed therapy:
  • S. pneumoniae: Amoxicillin 500 mg-1 g three times daily for 14 days; alternative: doxycycline 100 mg twice daily 3, 4
  • H. influenzae (beta-lactamase negative): Amoxicillin 500 mg three times daily for 14 days 3, 4
  • H. influenzae (beta-lactamase positive): Amoxicillin-clavulanate 625 mg three times daily for 14 days 3, 4
  • M. catarrhalis: Amoxicillin-clavulanate 625 mg three times daily for 14 days 3
  • S. aureus (MSSA): Flucloxacillin 500 mg four times daily for 14 days 3

For Patients WITH Pseudomonas aeruginosa

• Mild-to-moderate exacerbations (oral): Ciprofloxacin 500 mg twice daily (or 750 mg twice daily for more severe infections) for 14 days 3
• Severe exacerbations (intravenous): Ceftazidime 2 g three times daily, piperacillin-tazobactam 4.5 g three times daily, aztreonam 2 g three times daily, or meropenem 2 g three times daily for 14 days 3

For Patients with Multiple Drug Allergies

• Doxycycline 100 mg twice daily for 14 days provides coverage against S. pneumoniae, H. influenzae, and M. catarrhalis as a beta-lactam alternative 3
• Azithromycin 500 mg once daily for 14 days or erythromycin when doxycycline is not tolerated 3
• Aztreonam 2 g IV three times daily for 14 days for severe exacerbations requiring anti-pseudomonal coverage with minimal cross-reactivity to penicillins 3
• Inhaled colistin or tobramycin can be added to oral doxycycline as adjunctive therapy for P. aeruginosa in stable patients 3

Treatment Duration

The standard antibiotic course is 14 days for all bronchiectasis exacerbations, based on expert consensus and clinical outcome studies. 1, 3, 2

• Shorter courses (≤10 days) may be considered only for mild exacerbations with rapid return to baseline, though supporting evidence is limited 3
• Extended courses (>14 days) may be required for severe exacerbations or inadequate response at day 14 3

Contraindications and Safety Considerations

Absolute Contraindications

• Do NOT use inhaled corticosteroids for bronchiectasis treatment unless the patient has comorbid asthma or COPD 1, 3, 2
• Do NOT offer recombinant human DNase to adult patients with bronchiectasis 1
• Do NOT offer statins for bronchiectasis treatment 1, 3

Relative Contraindications and Precautions

• Long-term macrolides: Do not initiate without ensuring no active nontuberculous mycobacterial (NTM) infection with at least one negative respiratory NTM culture 4
• Aminoglycosides: Use with caution in patients with significant hearing loss or balance issues; avoid in patients with creatinine clearance <30 mL/min or those on concomitant nephrotoxic medications 4
• Antimicrobial resistance: Exercise antimicrobial stewardship to prevent resistance development, particularly with long-term therapy 4, 5

Monitoring Requirements

For Patients on Long-Term Antibiotics

• Review every 6 months to assess efficacy, toxicity, and continuing need 4, 2
• Monitor sputum culture and sensitivity regularly, recognizing that in vitro resistance may not correlate with clinical efficacy 4, 2

For Treatment Failure at Day 14

• Obtain repeat sputum culture and sensitivity testing 3
• Reassess for non-infectious causes (pulmonary embolism, heart failure, inadequate bronchodilator therapy) 3
• Escalate to broader-spectrum antibiotics guided by repeat culture results 3

Adjunctive Measures

• Increase frequency of airway clearance techniques during acute exacerbations compared to baseline 3
• Administer short-acting beta-2 agonists before airway clearance sessions and before inhaled antibiotics to facilitate sputum expectoration and optimize pulmonary deposition 1, 3
• Provide patients with a self-management plan including antibiotics to keep at home for prompt self-initiation at first sign of exacerbation 3

Common Pitfalls to Avoid

• Do not delay eradication therapy for first P. aeruginosa isolation—treat immediately to prevent chronic colonization 3, 4
• Do not start long-term antibiotics without first optimizing airway clearance and treating underlying causes 1, 2
• Do not assume in vitro antibiotic resistance predicts clinical failure—patients may still respond despite laboratory resistance 4, 2
• Consider allergy testing or graded beta-lactam challenge in patients with recurrent exacerbations to expand therapeutic options 3