Polymyxin E

Polymyxines Polymyxines are a gronp of related polypeptide antibiotics that are produced by sporo-forming soil bacteria Bacillus polymyxa and B. circulans, and they differ in amino acid content. Five different polymyxines have been identified—polymyxines A, B, C, D, and E, which differ in the amino acid content and are differentiated by additional letter notations and names— polymyxine B (aerosporin) and polymyxine E (colistin). It is known that in the process of development, some strains of B. polymyxa only form polymyxines A and C, and others synthesize polymyxines B and D. Polymyxine M was later isolated, a snlfomethyl derivative of polymyxine E. 

Polymyxine E is A-[3-amino-l-[[l-[[3-amino-l-[[6,9,18-fm(20 aminoethyl)-3-(l-hydrox-yethyl)-12,15-diisobutyl-2,5,8,11,14,17,20-heptaoxo-l,4,7,10,13,16,19-heptaazacyclotris-21-yl]-carbamoyl]-propyl]-carbamoyl]-2-hydroxypropyl]-carbamoyl]-propyl]-6-methyloctanam... 

The polymyxins are a group of antibiotics produced by Bacillus polymyxa. Polymyxin B (Aerosporin) and co-Ustin (polymyxin E, Coly-Mycin) are used in the treatment of bacterial diseases. 

Also known as polymyxin E, is also a cationic detergent used only orally. Side effects and uses are similar to polymyxin B. 

The polymyxins are a group of basic peptides active against gram-negative bacteria and include polymyxin and polymyxin E (colistin). Polymyxins act like cationic detergents. They attach to and disrupt bacterial cell membranes. They also bind and inactivate endotoxin. Gram-positive organisms, proteus, and neisseria are resistant. 

Polymyxin B and colistin (polymyxin E) (Fig. 3.9) are the least toxic of the five polymyxin antibiotics designated alphabetically A-E. Both polymyxin B and colistin are complex polypeptide compounds with specialized activity against gram-negative organisms but they are both nephrotoxic. Topical application and oral administration are more commonly used routes. Polymyxin B is used widely in ointments for topical applications and may be effective in case of mastitis, but it seldom is administered parenterally because of the possibility of renal toxicity. 

Colistin (COL) is a multicomponent antibiotic (polymyxins E) that is produced by strains of inverse Bacillus polymyxa. It consists of a mixture of several closely related decapeptides with a general structure composed of a cyclic heptapeptide moiety and a side chain acetylated at the N-terminus by a fatty acid. Up to 13 different components have been identified. The two main components of colistin are polymyxins El and E2 they include the same amino acids but a different fatty acid (216). A selective and sensitive HPLC method was developed for the determination of COL residues in milk and four bovine tissues (muscle, liver, kidney, and fat). The sample pretreatment consists of protein precipitation with trichloracetic acid (TCA), solid-phase purification on Cl 8 SPE cartridges, and precolumn derivatization of colistin with o-phthalaldehyde and 2-mercaptoethanol in borate buffer (pH 10.5). The last step was performed automatically, and the resulting reaction mixture was injected into a switching HPLC system including a precolumn and the reversed-phase analytical column. Fluorescence detection was used. The structural study of El and E2 derivatives was carried out by HPLC coupled with an electrospray MS. Recoveries from the preseparation procedure were higher than 60%. 

Colistin. Colistin (also known as colistimethate or polymyxin E) is similar to polymyxin B in terms of... 

Porous methacrylic acid-DVB resin having excellent sorptive-desorptive properties and suitable for the pharmaceutical isolation of polymyxin E can be prepared by the suspension copolymerization method... 

SYNS BELCOMYCIN COLIMYCIN SULFATE COLISTIN SULFAT COLISTIN SULFATE COUSTIN, SULFATE (SALT) COLOMYCIN SYRUP POLYMYXIN E SULFATE (SALT)... 

The overall sensitivity of Ps. aeruginosa to polymyxins appears unchanged for over twenty years [75] but although polymyxin E possesses reduced nephrotoxicity, this side effect is still a serious handicap. It has been suggested that polymyxins should not be used as preservatives in order to prevent any development of resistance that might occur [53]. 

Resistance to polymyxins. The polymyxins (A, B, C, D, E) are a group of antibiotics obtained from Bacillus polymyxa [145]. Polymyxin E is referred to as colistin. These antibiotics are extremely active against strains of Ps. aeruginosa but have the disadvantage of certain toxicity problems. The action of polymyxin is on the cytoplasmic membrane involving the phopholipid components [65,146]. 

The polymyxins that are used clinically are polymyxin B (rINN) and colistin (pINN, formerly known as polymyxin E). Colistimethate sodium (rINN, also called coUs-tin methanesulfonate and colistin sulfomethate sodium) is prepared from colistin. 

Polymyxin E (colistin) is used in the treatment of serious Gram-negative bacterial infections, particularly those caused by Pseudomonas aeruginosa. It binds tightly to the lipid A component of LPS in the outer membrane of Gram-negative bacteria. The outer leaflet of the membrane structure is distorted, segments of which are released and the permeability barrier is destroyed. The polymyxin mole-... 

Polymyxins. Polymyxin B [1404-26-8] and polymyxin E [1066-17-7] (colistin) are the only medically important antibacterials from a group of some thirty closely related cyclic decapeptide antibiotics in the polymyxin family, some of which are given in Table 2. Most family members contain a seven amino acid ring attached to a three amino acid tail, to which is attached a fatty acyl group. The octapeptins have a tail containing a single amino acid. Each antibiotic contains several L-a-y-diaminobutyric acid [1758-80-1], C4H10N2O2, (Dab) residues, L-threonine [72-19-5], at least one D-amino acid, and one of a very limited list of fatty acids. 

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