Polymyxin B and Colistin

Question 1

Structure

Answer 1

Polymyxins are cationic polypeptides linked to a fatty acid chain by an amide linkage.

Question 2

MOA

Answer 2

Polymyxins are cationic detergents that bind to the anionic lipopolysaccharide molecules of the out cell membrane of Gram (-) bacteria causing displacement of Mg and Ca, which leads to changes in cell wall permeability and leakage of cellular contents

Bactericidal–> concentration-dependent

Question 3

MOR

Answer 3

Alternation of the outer cell membrane–> decreased lipopolysaccharide content, decrease in Ca and Mg content, decreased outer membrane proteins

Question 4

Spectrum of activity

Answer 4

Gram (+) aerobes–> INACTIVE

Gram (-) aerobes
- PEEACKSSS
- Pseudomonas aeruginosa
- Acinetobacter spp.

Question 5

What bacteria are Polymyxins not active against?

Answer 5

Proteus and Serratia

Question 6

Absorption

Answer 6

Polymyxins are not absorbed from the GI tract; minimal systemic absorption has been reported after inhalation therapy

Question 7

Distribution

Answer 7

Colistin Vd= 0.17L/kg
Polymyxin B= 0.4L/kg

Does not penetrate the CSF

Question 8

Metabolism/Elimination

Answer 8

Polymyxin B and colistin are primarily eliminated by non-renal routes and do not require dosage adjustment in renal dysfunction

HOWEVER, 50% of CMS is excreted unchanged in the urine by glomerular filtration. CMS requires dose adjustments in CrCl < 80 mL/min

Question 9

Clinical uses

Answer 9

Infections caused by P. aeruginosa and Acinetobacter that are resistant to other antibiotics

Polymyxin B is preferred for system infections; colistin is preferred for UTI’s

Question 10

Adverse effects

Answer 10

Nephrotoxicity

Neurotoxicity

Question 11

CMS dosing

Answer 11

Use LBW for doses; dosing must be adjusted in renal insufficiency

Question 12

Polymyxin B dosing

Answer 12

Most current references do NOT recommend dosage adjustment in renal insufficiency

Use TBW for dosing