The polymyxins are a group of
antibiotics produced by Bacillus
polymyxa. Polymyxin B (Aerosporin)
and co-listin (polymyxin E, Coly-Mycin)
are used in the treat-ment of bacterial diseases.
The polymyxins are
polypeptide antibiotics that contain both hydrophilic and lipophilic regions.
These antibi-otics accumulate in the cell membrane and probably in-teract with
membrane phospholipids. Most likely the fatty acid portion of the antibiotic
penetrates the hy-drophobic portion of the membrane phospholipid and the
polypeptide ring binds to the exposed phosphate groups of the membrane. Such an
interaction would dis-tort the membrane, impair its selective permeability,
produce leakage of metabolites, and inhibit cellular processes. In the
laboratory polymyxin B can neutralize the effects of bacterial
lipopolysaccharide (LPS) of gram-negative organisms and may stimulate the
biosyn-thesis of complement component C3, factor B, inter-leukin
(IL) 6, and granulocyte-macrophage colony stimulating factor (GM-CSF). Its
clinical use in gram-negative sepsis has not been established. These
antibi-otics also are toxic to mammalian cells.
The polymyxins are active
against facultative gram-neg-ative bacteria, P. aeruginosa in particular.
Polymyxin B and colistin are
not well absorbed from the gastrointestinal tract. An intramuscular injection
of the polymyxins results in high drug concentrations in the liver and kidneys,
but the antibiotic does not enter the cerebrospinal fluid (CSF), even in the
pres-ence of inflammation.
The polymyxins are slowly
excreted by glomerular filtration; the slow elimination rate is due to binding
in tissues. Elimination is decreased in patients with renal disease, and drug
accumulation can lead to toxicity. Sodium colistimethate, the parenteral
preparation, binds less to tissue and is excreted faster than the free base.
With the advent of potent
broad-spectrum antibiotics, such as the quinolones and third-generation
cephalo-sporins, the indications for the
use of the polymyxins, with their
serious potential for toxicity, are few. Their only justifiable use may be as topical agents.
In combination with neomycin,
polymyxin B can be used as a bladder irrigant to reduce the risk of
catheter-associated infections, although this use remains contro-versial. It
also can be used as topical therapy in external otitis caused by P. aeruginosa.
Colistin and polymyxin B can
cause extreme nephro-toxicity when used parenterally, and any preexisting
re-nal insufficiency will potentiate the nephrotoxicity caused by these
Neurotoxicity is a rare
adverse reaction that can be recognized by perioral paresthesia, numbness,
weak-ness, ataxia, and blurred vision. These drugs may pre-cipitate respiratory
arrest both in patients given muscle relaxants during anesthesia and in persons
with myas-thenia gravis.