COLISTIN

Absorption

Very poor absorption from gastrointestinal tract.

Toxicity

Oral LD50 in rats is 5450 mg/kg. Overdosage with colistimethate can cause neuromuscular blockade characterized by paresthesia, lethargy, confusion, dizziness, ataxia, nystagmus, disorders of speech and apnea. Respiratory muscle paralysis may lead to apnea, respiratory arrest and death.

The Uses of COLISTIN

Polymyxin E (colistin) is a complex of closely related cyclic peptides E1 and E2, with additional minor analogues. Polymyxin E is produced by Bacillus polymyxa var. colistinus, and is a highly basic, atypical cyclic peptide which incorporates the unusual amino acid, diaminobutyric acid. Head-to-tail coupling of lysine completes the macrocycle. Balancing the polar cyclic peptide is a hydrophobic tail with short chain fatty acids. Polymyxin E is a broad spectrum antibiotic active against Gram negative bacteria. The mechanism of action involves disruption of the bacterial outer membrane by a detergent-like effect.

Background

Cyclic polypeptide antibiotic from Bacillus colistinus. It is composed of Polymyxins E1 and E2 (or Colistins A, B, and C) which act as detergents on cell membranes. Colistin is less toxic than Polymyxin B, but otherwise similar; the methanesulfonate is used orally.

Indications

For the treatment of acute or chronic infections due to sensitive strains of certain gram-negative bacilli, particularly Pseudomonas aeruginosa.

brand name

Coly-Mycin (Monarch).

Pharmacokinetics

Colistin is a polymyxin antibiotic agent. Polymyxins are cationic polypeptides that disrupt the bacterial cell membrane through a detergentlike mechanism. With the development of less toxic agents, such as extended-spectrum penicillins and cephalosporins, parenteral polymyxin use was largely abandoned, except for the treatment of multidrug-resistant pulmonary infections in patients with cystic fibrosis. More recently, however, the emergence of multidrug-resistant gram-negative bacteria, such as Pseudomonas aeruginosa and Acinetobacter baumannii, and the lack of new antimicrobial agents have led to the revived use of the polymyxins.

Metabolism

As 80% of the dose can be recovered unchanged in the urine, and there is no biliary excretion, it can be assumed that the remaining drug is inactivated in the tissues, however the mechanism is unknown.