EMmedonline

• Colistin consists of a cationic cyclic decapeptide linked to a fatty acid chain through an α-amide linkage.

• Two forms of colistin are available, colistin sulfate & colistimethate sodium . Colistimethate sodium is less potent and less toxic than colistin sulfate.

• Colistin sulfate is administrated orally for bowel decontamination and topically as a powder for treatment of bacterial skin infection.

• Colistimethate sodium is available in parenteral formulation and can be administrated intravenously, intramuscularly or by nebulisation.

Mechanism of Action

• The colistin is a cationic polypeptide which interacts with anionic lipopolysaccharide molecules in the outer membrane of the gram negative bacteria, leading to derangement of cell membrane.

• Colistin displaces magnesium & calcium which normally stabilize the LPS molecule; from the negatively charged LPS, leading to local disturbance of the outer membrane.

• This causes an increase in permeability of the cell envelope, leakage of cell contents & subsequently cell death.

• Colistin also has a potent endotoxin activity.

Spectrum

• It is a bactericidal and effective against most gram negative aerobic bacilli.

• It includes acinetobacter species, P. aeruginosa, Klebsiella species, Escherichia coli, Salmonella species, Shigella species, Citrobacter species, Yersinia pseudotuberculosis,H. Influenza. It is also potentially active mycobacterium species.

• But it is resistant to pseudomonas mallei, burkholderia cepacia,Proteus species, Providencia species, Serratia species, Edwardsiella species & Brucella species.

Dose

• Different countries have adopted different dosage

  • In US : 2.5 – 5.0 mg/kg in 2-4 divided doses

  • In UK: 4 – 6 mg/kg in 3 divided doses.

• Nebulisation

  • 1 million units BD

  • In severe cases 2 million units BD.

  • 1 million units is mixed with 4ml of NS and and nebulised using 8L of O2.

• Intrathecal

  • Dose : 3.2mg – 10mg/kg/d in divided doses.

Toxicity

• CNS : Dizziness, facial & peripheral parasthesia, vertigo, visula disturbance, confusion, ataxia & neuromuscular blockade.

• Generalised itching, fever & mild GI disorders.

• Aerosolised colistin may further be complicated by bronchoconstriction & chest tightness.

Coadministration with other antibiotic

• Studies have shown that combination therapy is more effective than monotherpay.

• Combination of colisitn with azlocillin, piperacillin, aztreonam, ceftazidime, imipenem or ciprofloxacin can be used.

• The combination of colistin, rifampin and amikacin are synergistic.