COLISTIN-600

Indications

• Treatment of multidrug-resistant gram-negative bacterial infections
• Pneumonia caused by Pseudomonas aeruginosa
• Complicated urinary tract infections
• Infections in cystic fibrosis patients

Dosage

Children: Refer to the BNF for Children for appropriate paediatric dosing information.

Adults: Refer to the BNF for specific dosing guidelines, as doses may vary based on infection severity and renal function.

Mechanism of action

Colistin interacts with the bacterial cytoplasmic membrane, disrupting its integrity and altering permeability. It binds to the membrane through its cationic properties, leading to leakage of essential intracellular components, which results in bactericidal effects.

Pharmacodynamics

Colistin functions as a cationic polypeptide that disrupts bacterial cell membranes via a detergent-like mechanism. It is effective against certain multidrug-resistant organisms, including Pseudomonas aeruginosa and Acinetobacter baumannii. Its use has increased due to the rise of antibiotic-resistant infections, particularly in patients with cystic fibrosis and other serious infections.

Pharmacokinetics

Colistin is administered parenterally and has variable pharmacokinetics depending on the route of administration. It is not well-absorbed orally and is primarily eliminated by the kidneys. The pharmacokinetic profile may vary based on renal function and dosage regimen, necessitating careful monitoring in patients with renal impairment.

Adverse effects

• Nephrotoxicity
• Neurotoxicity
• Allergic reactions
• Rash
• Fever

Interactions

• Increased risk of nephrotoxicity with other nephrotoxic agents
• Potential interactions with neuromuscular blockers

Precautions

• Monitor renal function during treatment
• Use with caution in patients with renal impairment
• Consider monitoring neuromuscular function in patients receiving concomitant neuromuscular blockers

Pregnancy

Colistin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether colistin is excreted in human milk. Caution should be exercised when administering to a nursing mother.

Storage

Store in a cool, dry place, away from light. Keep out of reach of children.

Formulations

• Colistin sulfate for injection
• Colistin methanesulfonate for injection

Mechanism of action

Colistin is a surface active agent which penetrates into and disrupts the bacterial cell membrane. Colistin is polycationic and has both hydrophobic and lipophilic moieties. It interacts with the bacterial cytoplasmic membrane, changing its permeability. This effect is bactericidal. There is also evidence that polymyxins enter the cell and precipitate cytoplasmic components, primarily ribosomes. POLYMYXIN B IS SURFACE-ACTIVE AGENT... CONTAINING LIPOPHILIC & LIPOPHOBIC GROUPS SEPARATED WITHIN MOLECULE. /POLYMYXIN B/ PERMEABILITY OF THE BACTERIAL MEMBRANE CHANGES IMMEDIATELY ON CONTACT WITH DRUG. SENSITIVITY TO POLYMYXIN B APPARENTLY IS RELATED TO THE PHOSPHOLIPID CONTENT OF THE CELL WALL-MEMBRANE COMPLEX. /POLYMYXIN B/ Colistin acts like a cationic detergent and binds to and damages the bacterial cytoplasmic membrane of susceptible bacteria. Damage to the bacterial cytoplasmic membrane alters the osmotic barrier of the membrane and causes leakage of essential intracellular metabolites and nucleosides.

Pharmacodynamics

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 <i>Pseudomonas aeruginosa</i> and <i>Acinetobacter baumannii</i>, and the lack of new antimicrobial agents have led to the revived use of the polymyxins.