Colistin Nebulization for Respiratory Infections Caused by Multidrug-Resistant Gram-Negative Bacteria
For respiratory infections caused by multidrug-resistant gram-negative bacteria, nebulized colistin should be administered at a dosage of 2 million IU every 8-12 hours, with higher doses of up to 5 million IU every 8 hours considered for non-resolving cases, and should always be used in combination with intravenous antimicrobial therapy. 1, 2
Indications and Patient Selection
- Nebulized colistin is indicated for patients with respiratory infections who are non-responsive to systemic antibiotics, have recurrent ventilator-associated pneumonia (VAP), or have infections with isolates showing minimum inhibitory concentrations (MICs) close to the susceptibility breakpoint 1, 2
- Particularly effective for treating respiratory infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) and multidrug-resistant Pseudomonas aeruginosa 1, 2
- Not recommended for use in patients with only airway colonization without active infection 1
Dosing and Administration
- Standard dosing regimen: 2 million IU every 8-12 hours 1, 2
- For non-resolving cases: Higher doses of up to 5 million IU every 8 hours may be considered 1, 2
- For critically ill patients: Dosing at the higher end of the range is recommended 2
- Administration should be via ultrasonic or vibrating plate nebulizers for optimal drug delivery 1, 2
- Important conversion: 1 million IU colistin methanesulfonate = 33 mg colistin base activity 1, 3
Combination Therapy Approach
- Nebulized colistin should always be used in combination with intravenous antimicrobial therapy for pneumonia, not as monotherapy 1, 4
- For CRAB pneumonia: Recommended combination is intravenous colistin (5 mg CBA/kg IV loading dose, then 2.5 mg CBA per [1.5 × CrCl + 30] IV q12h) plus adjunctive nebulized colistin 1
- Intravenous colistin may be combined with high-dose extended-infusion carbapenem (if carbapenem MIC ≤32 mg/L) for synergistic effect 1
- Combined therapy has been shown to reduce clinical treatment failure by approximately 77 cases per 1000 patients treated compared to intravenous therapy alone 1
Monitoring and Safety Considerations
- Monitor for bronchospasm, which can occur during nebulization, especially in patients with underlying respiratory conditions 1, 5
- Renal function should be closely monitored, though nebulized administration has lower risk of nephrotoxicity compared to intravenous administration 3, 6
- Systemic absorption of nebulized colistin occurs but typically remains below nephrotoxic thresholds 1, 2
- Recent evidence suggests nebulized colistin is well-tolerated even in patients with chronic respiratory diseases such as COPD 5
Treatment Duration
- For pneumonia caused by CRAB: At least 7 days of treatment is recommended 1
- For ventilator-associated pneumonia: 10-14 days is typically recommended 1
- Consider monitoring microbiological response to guide treatment duration in difficult cases 1
Clinical Efficacy
- Combined intravenous and nebulized colistin therapy has been associated with:
Common Pitfalls and Caveats
- Ensure proper nebulizer selection - ultrasonic or vibrating plate nebulizers are superior to jet nebulizers for colistin delivery 1, 2
- Be aware that colistin formulations vary globally - colistimethate sodium (CMS) is preferred for inhalation therapy 1, 7
- Avoid using nebulized colistin as monotherapy except in specific cases of chronic infections with P. aeruginosa in cystic fibrosis patients 4
- Remember that the evidence supporting nebulized colistin is of low to moderate quality, and treatment decisions should prioritize mortality and morbidity outcomes 1, 2