Colistin

Abstract

Colistin (polymyxin E) is a positively charged deca-peptide antibiotic that disrupts the integrity of the outer membrane of the cell wall of gram-negative bacteria by binding to the lipid A moiety of lipopolysaccharides, resulting in cell death. The endotoxic activity of lipopolysaccharides is simultaneously inhibited. Colistin is increasingly being prescribed as rescue treatment for infections with multidrug-resistant bacilli. Nephrotoxicity and, to a lesser degree, neurotoxicity occur often during systemic colistin therapy, and have severely limited its application in the past. However, these side effects are largely reversible and can be managed through close monitoring. The prodrug colistimethate sodium (CMS) is less toxic and is, therefore, the preferred formulation for parenteral administration. Importantly, resistance to colistin seems to emerge often unless it is combined with another antibiotic, but further studies into this phenomenon are necessary. Pharmacokinetic and pharmacodynamic properties have received little attention, partly because of the physicochemical peculiarities of polymyxin antibiotics, especially their propensity to stick to other molecules and surfaces. The ratio between the area under the curve of free colistin and the pathogen's Minimal Inhibitory Concentration (MIC) best predicts microbiological and clinical responses, but more studies are needed in this area. Likewise, further standardization is needed in production and labeling of colistin formulations, and in the way the susceptibility of bacteria to colistin is determined.

Colistin in Pig Production: Chemistry, Mechanism of Antibacterial Action, Microbial Resistance Emergence, and One Health Perspectives

“…Colistin (polymyxin E) is a polymyxin antibiotic produced by Paenibacillus polymyxa var colistinus (Tambadou et al, 2015) consisting of a cyclic heptapeptide ring with three positively charged amine groups, a tail tripeptide moiety with two positively charged amine groups, and a hydrophobic acyl chain tail ( Figure 1 ; Li et al, 2006; Bergen et al, 2012; Azzopardi et al, 2013; Dijkmans et al, 2015; Rhouma et al, 2015). Colistin is an amphipathic molecule, with hydrophobicity mainly attributable to the fatty acyl moiety and hydrophilicity due to the five L -diaminobutyric acid ( L -Dab) amino groups (Li et al, 2006).…”

“…These amino groups are responsible for the electrostatically interaction between colistin and the lipid A portion of LPS molecules of GNB and play a central role in the bactericidal activity of colistin (Azzopardi et al, 2013). The polymyxins family includes five chemically distinct compounds (polymyxins A–E) and only colistin (polymyxin E) and polymyxin B have been used in clinical practice (Dijkmans et al, 2015). Polymyxin B and colistin share a similar primary sequence with the only difference being one amino acid in position 6 in which D - phenylalanine in polymyxin B is replaced by D - leucine in colistin ( Figure 1 ; Li et al, 2006; Velkov et al, 2009; Biswas et al, 2012; Yoshino et al, 2013; Gallardo-Godoy et al, 2016).…”

“…Colistin has a narrow antibacterial spectrum with an effect limited to GNB; Gram-positive bacteria do not contain LPS in their cell wall and, as a consequence, are excluded from the spectrum of activity of polymyxins (Dijkmans et al, 2015). …”

Therapeutic cyclic lipopeptides mining from microbes: latest strides and hurdles

“…(DeCrescenzo Henriksen et al 2007;Yoshino et al 2013). Polymyxin E or colistin has got wide commercial application (Lim et al 2010;Dijkmans et al 2014). Also, polymyxin B is another commercially licensed lipopeptide from this group (Kwa et al 2007).…”

Defeating Antibiotic-Resistant Bacteria: Exploring Alternative Therapies for a Post-Antibiotic Era

“…Most identified colistin resistance mechanisms in Gram-negative bacteria involve changes to the lipopolysaccharide (LPS) structure, as colistin initially interacts with the negatively charged lipid A of LPS [17,18]. Importantly, plasmid-borne phosphoethanolamine transferases (mcr-1 to mcr-8) have recently been identified and these plasmids threaten to increase the rate of dissemination of clinically relevant colistin resistance in CRE [18].…”