Colistin

Indications

Colistin is indicated for the treatment of both acute and chronic infections caused by susceptible strains of certain gram-negative bacilli, with a particular emphasis on Pseudomonas aeruginosa. It is utilized in circumstances where these pathogenic bacteria are present and sensitive to colistin's mechanism of action, thereby proving effective in combating otherwise difficult-to-treat infections.

Pharmacodynamics

Colistin functions as a polymyxin antibiotic, and its pharmacodynamic activity stems from its nature as a cationic polypeptide. This allows it to interact with and disrupt bacterial cell membranes through a mechanism akin to detergent action. Historically, the use of parenteral polymyxins waned with the advent of less toxic antibiotics such as extended-spectrum penicillins and cephalosporins. However, the resurgence in the use of colistin has been necessitated by the increasing prevalence of multidrug-resistant gram-negative bacteria, such as Pseudomonas aeruginosa and Acinetobacter baumannii, especially in treating pulmonary infections in patients with conditions like cystic fibrosis.

Absorption

Colistin demonstrates very poor absorption when administered via the gastrointestinal tract. This necessitates the use of alternative routes of administration for systemic infections to ensure that adequate therapeutic concentrations are achieved in the bloodstream and at the site of infection.

Metabolism

In terms of metabolism, approximately 80% of colistin is recoverable in the urine in its unchanged form, indicating minimal metabolic alteration and lack of biliary excretion. The remaining portion of the dose is presumed to be inactivated within the tissues; however, the exact metabolic pathways responsible for this inactivation remain unidentified.

Mechanism of Action

Colistin operates as a surface-active agent with the ability to penetrate and disrupt bacterial cell membranes. Owing to its polycationic nature and the presence of both hydrophobic and lipophilic segments, colistin interacts effectively with the bacterial cytoplasmic membrane, altering its permeability. This interaction ultimately results in a bactericidal effect. Additionally, evidence suggests that polymyxins, such as colistin, can enter the bacterial cell and precipitate cytoplasmic components, particularly targeting ribosomes.