Colistin: An Update on the Antibiotic of the 21st Century

Silpak Biswas; Jean-Michel Brunel; Jean-Christophe Dubus; Martine Reynaud-Gaubert; Jean-Marc Rolain

Disclosures

Expert Rev Anti Infect Ther. 2012;10(8):917-934. 

In This Article

Mode of Action of Colistin

The bacterial cell membrane is the initial site of action for colistin.[1,2,10] Colistin binds to LPSs and phospholipids in the outer cell membrane of Gram-negative bacteria. It competitively displaces divalent cations (Ca2+ and Mg2+) from the phosphate groups of membrane lipids, which leads to disruption of the outer cell membrane, leakage of intracellular contents and bacterial death (Figure 3).[1,3,10,13,15,53,54]

Figure 3.

Antimicrobial mode of action of polymyxin against Gram-negative bacterial membranes. LPS: Lipopolysaccharide.

With electron microscopic examination, previous studies showed the bacterial cytoplasmic membrane to be partially damaged and part of the cytoplasmic material released in fibrous forms through cracks.[55] Hydrophilic antibiotics such as rifampicin, carbapenems, glycopeptides and tetracyclines can work synergistically owing to the disruption of membrane integrity by colistin.[56] Some reports showed that polymyxins act through an alternative mode of action, other than acting on bacterial cell membrane.[57,58] Therefore, the exact mechanism(s) by which colistin ultimately kill bacterial cells is still unknown.

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