What is the recommended dose and duration of therapy for colistin and tobramycin (Tobramycin) in non-cystic fibrosis bronchiectasis?

Dosing and Duration of Colistin and Tobramycin in Non-Cystic Fibrosis Bronchiectasis

For patients with non-cystic fibrosis bronchiectasis and Pseudomonas aeruginosa infection, inhaled colistin should be administered at 1 million units twice daily for 3 months, while inhaled tobramycin should be given at 300 mg twice daily for 4-12 weeks. 1

Dosing Recommendations

Colistin

• Recommended dose: 1 million units twice daily 1, 2
• Duration: 3 months for eradication therapy 2, 1
• Administration: Via nebulizer, after appropriate airway clearance techniques 2

Tobramycin

• Recommended dose: 300 mg twice daily 1, 3
• Duration: 4-12 weeks (typically used for 3 months in eradication protocols) 1, 2
• Administration: Via nebulizer, may require pre-treatment with bronchodilators to prevent bronchospasm 4

Treatment Approach: Cycles vs. Continuous Therapy

Eradication Protocol (First Isolation)

• Initial phase (first 2 weeks): Oral ciprofloxacin 750 mg twice daily OR intravenous antibiotics (beta-lactam plus aminoglycoside) 2
• Continuation phase: Add inhaled antibiotics (colistin or tobramycin) for a total duration of 3 months 2, 1
• Monitor with repeat sputum cultures to confirm eradication 2

Chronic Pseudomonas Infection

• Cyclic approach: The British Thoracic Society recommends inhaled colistin for patients with chronic Pseudomonas aeruginosa infection 4
• Continuous therapy: For patients with frequent exacerbations, continuous therapy may be considered 2
• Alternating therapy: Some evidence suggests that alternating tobramycin and colistin may reduce hospitalization days and antibiotic use compared to tobramycin alone 5

Efficacy Considerations

• Tobramycin has shown greater improvement in lung function (6.7% increase in FEV1) compared to colistin (no significant improvement) in short-term studies 6
• Colistin has demonstrated reduced hospitalization rates and decreased Pseudomonas density in sputum 7
• Both treatments have shown effectiveness in reducing bacterial load 6
• Combined therapy with both colistin and tobramycin may be associated with fewer days of hospitalization and shorter duration of antibiotic treatment 5

Safety and Monitoring

• Monitor for bronchospasm, particularly with tobramycin (reported in up to 50% of patients) 4, 3
• Pre-treatment with bronchodilators is recommended to prevent bronchospasm 4
• Regular monitoring of sputum cultures is essential to track bacterial density and development of resistance 4
• Avoid inhaled aminoglycosides if creatinine clearance is <30 mL/min 1
• Use with caution in patients with significant hearing loss or balance issues 1

Important Caveats

• Neither inhaled tobramycin nor colistin has FDA approval specifically for non-CF bronchiectasis 4
• Emergence of resistance to colistin appears to be lower than resistance to tobramycin 5
• Patients on long-term antibiotics should be reviewed every 6 months to assess efficacy, toxicity, and continuing need 1
• Inhaled antibiotics should only be initiated by respiratory specialists 1

Clinical Decision Algorithm

1. For first isolation of P. aeruginosa:

   • Start with oral ciprofloxacin 750 mg twice daily for 2 weeks 2
   • Add inhaled colistin (1 million units twice daily) or tobramycin (300 mg twice daily) for a total of 3 months 2, 1

2. For chronic P. aeruginosa infection:

   • First-line: Inhaled colistin 1 million units twice daily 4
   • Alternative: Inhaled tobramycin 300 mg twice daily if colistin not tolerated 1, 4
   • Consider combination therapy in patients with severe disease or frequent hospitalizations 5