Spectrum of Activity: Colistin and Polymyxin B
Colistin and polymyxin B are bactericidal agents with nearly identical activity against most gram-negative bacilli, specifically targeting Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae, while having no activity against gram-positive bacteria, fungi, gram-negative cocci, or Proteus species. 1, 2
Core Spectrum Coverage
Highly Susceptible Organisms
- Carbapenem-resistant Pseudomonas aeruginosa (CRPA): Both polymyxins demonstrate excellent potency with MIC₉₀ of 2 mcg/mL 3
- Carbapenem-resistant Acinetobacter baumannii (CRAB): MIC₉₀ of 2 mcg/mL, making polymyxins a primary treatment option 3, 4
- Carbapenem-resistant Enterobacterales (CRE): Including Klebsiella pneumoniae, Enterobacter aerogenes, and Escherichia coli 2, 5
Organisms with Limited or No Activity
- Proteus species: Intrinsically resistant to all polymyxins 1
- Burkholderia cepacia: Poor activity with MIC₉₀ ≥128 mcg/mL 3
- All gram-positive bacteria: Complete resistance 1
- Fungi: No antifungal activity 1
- Gram-negative cocci: Resistant 1
Mechanism of Action
- Polymyxins are amphipathic molecules that interact with lipopolysaccharide in the bacterial outer membrane, increasing permeability and leading to cell death 1, 6
- They possess potent antiendotoxic properties in addition to their bactericidal effects 6
- The mechanism results in rapid bactericidal activity against susceptible gram-negative bacteria 7
Clinical Context for Use
Primary Indications
- Last-resort therapy for multidrug-resistant gram-negative infections when carbapenem-resistant organisms are susceptible only to polymyxins 8, 5
- Recommended for severe infections caused by CRAB, CRPA, and CRE when newer agents (ceftolozane-tazobactam, ceftazidime-avibactam) are unavailable or inactive in vitro 5, 9
Important Limitations
- Poor tissue penetration: Does not cross the blood-brain barrier into cerebrospinal fluid, requiring intrathecal/intraventricular administration for CNS infections 1, 8
- Serum activity reduction: Polymyxin B loses 50% of its activity in the presence of serum, resulting in lower active blood levels 1
- Nephrotoxicity: Occurs in 10.9-53.7% of patients, with colistin showing higher nephrotoxicity than polymyxin B (adjusted HR 2.27,95% CI 1.35-3.82) 5, 9
Resistance Patterns
- Acquired resistance remains rare among major MDR gram-negative pathogens, though emerging resistance is a concern with increased use 7, 10
- Combination therapy may help prevent emergence of resistant subpopulations during treatment 5, 9
Practical Testing Considerations
- MIC testing is mandatory: Disk diffusion methods have unacceptable error rates (≥3.5% false-susceptible results) and should not be used alone 3
- Resistance breakpoint is ≥4 mcg/mL for both agents 3
- Testing against polymyxins is recommended for carbapenem-resistant gram-negative bacteria resistant to all β-lactams 5