What is the recommended treatment regimen for colistin (polymyxin E) nebulization in patients with respiratory infections caused by multidrug-resistant gram-negative bacteria?

Recommended Treatment Regimen for Colistin Nebulization in Respiratory Infections

For patients with respiratory infections caused by multidrug-resistant gram-negative bacteria, nebulized colistin should be administered at a dose of 2 million IU every 8-12 hours, with higher doses of 5 million IU every 8 hours considered for non-resolving cases, delivered via ultrasonic or vibrating plate nebulizers. 1

Indications for Nebulized Colistin

• Nebulized colistin is recommended 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
• Particularly beneficial for treating respiratory infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) and multidrug-resistant Pseudomonas aeruginosa 1
• Effective for both ventilator-associated pneumonia and ventilator-associated tracheobronchitis 1, 2

Dosing Recommendations

• Standard dosing: 2 million IU every 8-12 hours 1
• For non-resolving cases: Higher doses of 5 million IU every 8 hours may be used 1
• In critically ill patients: Consider higher dosing regimens delivered via vibrating plate nebulizers 1
• Nebulized colistin should be delivered using ultrasonic or vibrating plate nebulizers for optimal drug delivery 1

Combination Therapy Considerations

• In patients with pneumonia, nebulized colistin should always be used in combination with intravenous antimicrobial therapy 1
• For ventilator-associated tracheobronchitis, nebulized antibiotics are recommended, though further studies are needed to determine if intravenous therapy is also necessary 1
• For CRAB pneumonia, colistin (with or without carbapenems) plus adjunctive inhaled colistin therapy is recommended 1

Selection of Antimicrobial Agent

• The choice between colistin or an aminoglycoside for nebulization should be based on susceptibility results 1
• For isolates susceptible to both aminoglycosides and colistin, either can be selected as there is no definitive recommendation on which is superior 1
• Tigecycline monotherapy is not recommended for the treatment of CRAB pneumonia 1

Monitoring and Safety Considerations

• Renal function should be closely monitored during colistin therapy, as acute kidney injury is a significant risk factor for clinical failure and mortality 1
• Systemic absorption of nebulized antibiotics has been confirmed, though trough serum concentrations typically remain below the renal toxicity threshold 1
• Nebulized colistin should not be used in patients with only A. baumannii colonization (without active infection) 1

Efficacy Evidence

• Clinical studies have demonstrated that aerosolized colistin for MDR gram-negative pneumonia increases cure rates and is reasonably efficacious and safe 1
• A retrospective case-control study showed a higher rate of clinical cure with nebulized colistin in microbiologically documented VAP caused by colistin-only susceptible gram-negative bacteria 1
• Pooled data from studies shows clinical success rates of approximately 70% and eradication of gram-negative bacteria in about 71% of cases with inhaled colistin monotherapy 2

Special Considerations

• Inhaled colistin may be particularly valuable for treating infections caused by extensively drug-resistant or pan-drug-resistant organisms 1
• The physico-chemical characteristics of colistin impair crossing of the alveolo-capillary membrane but enable disruption of the bacterial wall of gram-negative bacteria, making it particularly effective when delivered directly to the respiratory tract 3
• For patients with tracheobronchitis due to MDR gram-negative bacteria, nebulized colistin has shown encouraging results for microbiological eradication and clinical cure 1