Lung Penetration: Colistin vs Polymyxin B
For critically ill intubated adults with multidrug-resistant Gram-negative pneumonia, colistin (administered as colistin methanesulfonate/CMS) achieves superior lung penetration compared to polymyxin B, particularly when delivered via inhalation, making it the preferred polymyxin for respiratory tract infections.
Pharmacokinetic Evidence
The key distinction lies in how these agents reach the lung tissue:
Colistin methanesulfonate (CMS) is an inactive prodrug that converts to active colistin. When administered as an aerosol, approximately 9% of the CMS dose reaches the epithelial lining fluid (ELF), with 1.4% undergoing presystemic conversion to active colistin 1. This results in dramatically higher ELF concentrations (9.53 to 1,137 mg/L) compared to plasma levels (0.15 to 0.73 mg/L) after aerosol delivery 1.
Polymyxin B, in contrast, has poor tissue diffusion and does not cross biological barriers effectively 2. The FDA label explicitly states that "tissue diffusion is poor" and the drug "loses 50 percent of its activity in the presence of serum" 2. This pharmacokinetic disadvantage significantly limits its lung penetration when given intravenously.
Clinical Guideline Recommendations
The most recent 2023 guidelines specifically address this issue: CMS is preferred for inhalation therapy over polymyxin B sulfate, even though both intravenous polymyxin preparations are technically appropriate 3. The guidelines recommend using aerosolized polymyxin in addition to intravenous polymyxin for carbapenem-resistant Gram-negative bacilli (CRGNB) respiratory tract infections 3.
The 2016 IDSA/ATS guidelines similarly recommend inhaled colistin (not polymyxin B) as adjunctive therapy, noting that "inhaled colistin may have potential pharmacokinetic advantages compared to inhaled polymyxin B" 4. They explicitly state they are "not suggesting use of inhaled polymyxin B" due to lack of controlled clinical evidence 4.
Clinical Implications for Practice
For pneumonia specifically:
- Intravenous colistin alone: Achieves suboptimal lung concentrations
- Aerosolized colistin: Delivers high local concentrations with minimal systemic exposure
- Combined IV + inhaled colistin: May reduce mortality by 50 per 1000 patients and clinical treatment failure by 77 per 1000 patients compared to IV alone 3
Recent comparative data shows that aerosolized colistin achieved significantly shorter time to defervescence (3.0 ± 1.2 days vs 5.0 ± 1.7 days for IV) and demonstrated 72.1% clinical efficacy as monotherapy 5, 6.
Safety Considerations
A critical advantage of inhaled colistin is reduced nephrotoxicity. Polymyxin B shows significantly higher rates of severe acute kidney injury (stages II-III) compared to colistin sulfate (OR = 6.865) 7. This is particularly pronounced in CRAB infections, where polymyxin B carries 7.63-fold higher odds of severe AKI 7.
Common Pitfalls to Avoid
- Do not use polymyxin B for inhalation - it lacks the clinical evidence and pharmacokinetic advantages of colistin 4
- Monitor for bronchospasm when administering inhaled colistin 3
- Use proper dosing: 9 MU loading dose, then 4.5 MU twice daily for IV colistin 8
- Administer inhaled colistin promptly after mixing with sterile water 4
The evidence consistently demonstrates that colistin's prodrug formulation and conversion characteristics provide superior lung penetration, making it the rational choice for pneumonia over polymyxin B.