Mellistin Mechanism of Action

Pharmacology: Pharmacodynamics: Colistimethate sodium is the sulfamethyl derivative of Colistin. Colistin or Polymyxin E is a Polymyxin antibiotic obtained from Bacillus polymyxa var. Colistinus that is active against many gram-negative bacilli and inactive against gram-positive bacteria, fungi, and viruses. The mechanism of action is bactericidal. Colistimethate (Colistin-methanesulfonate) is hydrolyzed to Colistin which acting like a cationic detergent and binds to the bacterial cytoplasmic membrane of susceptible bacteria. This alters permeability and causes leakage of bacterial cell wall. This leads to bacterial death. In vitro, Colistin is active against these bacteria as follows.
Aerobic gram-negative bacteria: Acinetobacter sp., Acinetobacter baumannii, Citrobacter sp., Escherichia coli, Enterobacter aerogenes, Haemophilus influenzae, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella sp., Shigella sp. and some strains of Bordetella sp., Vibrio sp.
Some bacteria have been reported resistance to Colistin. Those are Proteus sp., Providencia sp., Serratia sp., Neisseria gonorrhoeae, N. meningitidis, and Bacteriodes fragilis.
Pharmacokinetics: Colistimethate sodium is not absorbed from the GI tract and must be given parenterally. The drug is widely distributed into body tissues such as the liver, kidneys, lung, heart, and muscle. In patients with normal or inflamed meninges, only minimal concentrations of antimicrobial activity are attained in cerebrospinal fluid (CSF). More than 50% of Colistin bound to serum proteins. It also crosses the placenta and is distributed into milk. Colistimethate sodium is hydrolyzed to Colistin and possibly other metabolites with fewer substituted amino groups. The plasma half-life of Colistimethate sodium is 1.5-8 hours in adults with normal renal function and is prolonged in patients with impaired renal function. Both Colistimethate sodium and metabolites of the drug are excreted mainly by the kidneys.
Colistimethate sodium may be removed by hemodialysis and, to a lesser extent, by peritoneal dialysis.