What is the duration of a 28 days on and 28 days off treatment cycle with inhaled tobramycin for cystic fibrosis (CF) patients and is inhaled colistin administered on the same schedule?

Inhaled Tobramycin and Colistin Treatment Schedule in Cystic Fibrosis

For patients with cystic fibrosis and chronic Pseudomonas aeruginosa infection, inhaled tobramycin should be administered in 28-day on/28-day off cycles continuously as long-term maintenance therapy, while colistin is typically administered daily without off periods.

Inhaled Tobramycin Administration

• Inhaled tobramycin is administered in intermittent cycles of 28 days on treatment followed by 28 days off treatment, which is the FDA-approved regimen for long-term maintenance therapy in CF patients with P. aeruginosa infection 1, 2
• This 28-day on/28-day off cycle is continued indefinitely as part of regular maintenance treatment for chronic P. aeruginosa infection 1, 3
• The recommended dose for tobramycin inhalation is 300 mg twice daily during the 28-day on periods 4
• Clinical trials have demonstrated that this intermittent administration improves lung function, decreases P. aeruginosa density in sputum, and reduces hospitalization risk 3

Colistin Administration

• Unlike tobramycin, inhaled colistin is typically administered continuously without off periods, at a dose of 1-2 million units twice daily 1
• Colistin is widely used for maintenance therapy and for eradication of early colonization/infection with P. aeruginosa 1
• Efficiency has been shown at doses ranging from 1 million units twice daily to 2 million units three times daily 1
• There is no evidence supporting an intermittent 28-day on/28-day off cycle for colistin as is used with tobramycin 5

Duration of Therapy

• Both inhaled tobramycin and colistin are used as long-term maintenance therapies for patients with chronic P. aeruginosa infection 1
• The European Respiratory Society consensus recommends that CF patients with chronic P. aeruginosa infection should receive either 3-4 times yearly intravenous antibiotics or appropriate aerosol administration using either colistin or tobramycin throughout the year 1
• There is no defined endpoint to this therapy - treatment continues indefinitely as part of chronic disease management [1, @21@]

Comparative Efficacy

• Comparative studies show tobramycin is superior to colistin in CF patients, with one study demonstrating tobramycin increased FEV1 by 6.7% while colistin showed no measured improvement in lung function 1, 5
• The Cystic Fibrosis Foundation strongly recommends inhaled tobramycin (Grade A recommendation) for CF patients 6 years and older with moderate to severe lung disease and persistent P. aeruginosa 5
• The evidence for colistin is less robust, with the Cystic Fibrosis Foundation stating there is insufficient evidence to recommend colistin for routine use in CF patients (Grade I recommendation) 1

Safety Considerations

• The major side effect of nebulized antibiotic therapy is bronchospasm 1
• Pre-treatment with bronchodilators is recommended to prevent bronchospasm with either medication 1, 6
• Airway clearance techniques should be performed before inhalation to improve drug delivery 1, 6
• There is no evidence of renal toxicity or auditory toxicity when inhaled antibiotics are used alone, but caution is needed when patients receive intravenous aminoglycosides in addition to high-dose aerosolized antibiotics 1

Important Clinical Considerations

• Regular monitoring through sputum cultures is essential with either medication to track bacterial density and development of resistance 5, 6
• Resistance to colistin appears to develop less frequently than resistance to tobramycin 1
• As more inhaled antibiotics become available, continuous therapy by cycling multiple inhaled antibiotics may be considered, though this approach requires further study 1
• The treatment burden of multiple daily inhaled medications should be considered when designing treatment regimens 1