Is there an FDA-approved regimen for inhaled tobramycin (Tobramycin) or colistin (Colistin) for non-cystic fibrosis bronchiectasis?

FDA Approval Status of Inhaled Tobramycin and Colistin for Non-Cystic Fibrosis Bronchiectasis

Neither inhaled tobramycin nor colistin are FDA-approved for use in non-cystic fibrosis bronchiectasis, despite their clinical use in this population. 1

Current Approval Status and Evidence

• Inhaled tobramycin is FDA-approved for cystic fibrosis bronchiectasis in patients 6 years and older with Pseudomonas aeruginosa infection, but not for non-CF bronchiectasis 1
• Inhaled colistin similarly lacks FDA approval for non-CF bronchiectasis treatment 2, 3
• The European Respiratory Society guidelines state there is insufficient evidence to recommend routine use of nebulized tobramycin in non-CF bronchiectasis 2, 1

Clinical Evidence for Non-CF Bronchiectasis

Tobramycin

• Small studies show mixed results in non-CF bronchiectasis patients with P. aeruginosa infection:
  • Some evidence suggests decreased hospitalization rates (from 1.24 ± 1.36 to 0.52 ± 0.91, p=0.019) and improved symptoms with tobramycin inhalation therapy 4
  • A double-blind, placebo-controlled crossover trial found lower hospital admissions during tobramycin treatment compared to placebo (0.15 ± 0.37 vs 0.75 ± 1.16, p<0.047) 5
  • However, no significant improvements were observed in pulmonary function or quality of life 5

Colistin

• Limited evidence exists for inhaled colistin in non-CF bronchiectasis:
  • The British Thoracic Society (BTS) guidelines recommend inhaled colistin for patients with bronchiectasis and chronic Pseudomonas aeruginosa infection (Grade B recommendation) 2
  • However, comparative studies show colistin is less effective than tobramycin, with one study showing no improvement in lung function with colistin while tobramycin increased FEV1 by 6.7% 2

Safety Considerations

• Adverse respiratory effects are more common in non-CF bronchiectasis patients than in CF patients 3
• Bronchospasm is a significant concern, reported in multiple studies:
  • Wheezing observed in 50% of patients treated with inhaled tobramycin in one study 2
  • Bronchospasm reported in 3 patients in another trial 5
  • Increased dyspnea after nebulization is a common side effect 4
• Patients with kidney disease or ear disorders should be treated with caution due to potential systemic absorption 1, 3

Treatment Approach Based on Current Evidence

• For patients with non-CF bronchiectasis and chronic P. aeruginosa infection who have frequent exacerbations:
  • The BTS guidelines suggest using inhaled colistin as first-line therapy 2
  • Inhaled gentamicin can be considered as a second-line alternative 2
  • Macrolides (azithromycin or erythromycin) may be used as alternatives if patients cannot tolerate inhaled antibiotics 2

Important Caveats

• Treatment is considered off-label in non-CF bronchiectasis 6
• Pre-treatment with bronchodilators is recommended to prevent bronchospasm 1
• Regular monitoring through sputum cultures is essential to track bacterial density and development of resistance 1
• Treatment should be discontinued if no benefit is observed within three months (less sputum, fewer exacerbations) 7

While these medications are used clinically for non-CF bronchiectasis, their off-label status requires careful consideration of risks and benefits for each patient, with particular attention to respiratory adverse effects which appear more common in this population than in CF patients.