What is the difference between colistin and polymyxin B (polymyxin antibiotics)?

Differences Between Colistin and Polymyxin B

Colistin (polymyxin E) and polymyxin B have important pharmacokinetic and pharmacodynamic differences that affect their clinical use, with polymyxin B generally having superior clinical pharmacological properties compared to colistin.

Chemical Structure and Administration

• Both are polypeptide antibiotics from the polymyxin family with similar chemical structures, differing by only one amino acid 1, 2
• Polymyxin B is administered directly in its active form, while colistin is administered as an inactive prodrug called colistimethate sodium (CMS) that requires in vivo conversion 3, 4
• One million international units (IU) of colistin is equivalent to 80 mg of colistimethate sodium (CMS) 4

Pharmacokinetics

• Colistin's prodrug (CMS) must undergo conversion in vivo, which occurs slowly and incompletely, leading to delayed achievement of therapeutic levels 3, 5
• Polymyxin B does not require conversion and achieves more predictable and reliable blood concentrations 3
• Both drugs have poor tissue diffusion and do not cross the blood-brain barrier 6
• Both are excreted primarily by the kidneys, though polymyxin B has less renal clearance than colistin 5, 6

Antimicrobial Activity

• Both have bactericidal activity against most gram-negative bacilli except Proteus species 6
• Polymyxin B has been shown to have significantly lower minimum inhibitory concentrations (MICs) against key multidrug-resistant pathogens including Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa 1
• Both increase bacterial cell membrane permeability, leading to cell death 6

Dosing Considerations

• Colistin requires a loading dose of 9 million IU regardless of renal function, followed by maintenance doses of 4.5 million IU every 12 hours in patients with normal renal function 4
• Polymyxin B dosing is more straightforward as it doesn't require conversion from a prodrug 3
• Both drugs require dose adjustments in renal impairment, but polymyxin B requires less adjustment than colistin 7

Nephrotoxicity

• Colistin is associated with higher rates of nephrotoxicity compared to polymyxin B (Risk Ratio = 1.55,95% CI 1.36-1.78) 8
• Colistin-associated nephrotoxicity occurs earlier and is more frequent than with polymyxin B 8, 9
• For patients on continuous renal replacement therapy, polymyxin B may be a suitable alternative as it doesn't require dose adjustment during CRRT 7

Clinical Implications

• For inhaled administration, colistin is preferred over polymyxin B based on clinical evidence from controlled studies 9
• For intravenous administration in patients with renal impairment, polymyxin B may have advantages due to less nephrotoxicity 8, 9
• In hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP) caused by carbapenem-resistant pathogens sensitive only to polymyxins, either agent can be used intravenously, with a suggestion for adjunctive inhaled colistin 9

Monitoring

• Both drugs require close monitoring of renal function during therapy 4, 7
• Solutions of both drugs should be stored under refrigeration, with unused portions discarded after 72 hours 6

Practical Considerations

• Polymyxin B should not be stored in alkaline solutions as they are less stable 6
• Colistin for inhalation should be administered promptly after being mixed with sterile water to prevent complications 9

In summary, while both antibiotics have similar antimicrobial spectra, polymyxin B offers more predictable pharmacokinetics and potentially less nephrotoxicity, making it potentially preferable in patients with renal impairment or those at high risk for kidney injury.