Polymyxin B sulfate

Description

The polymyxins are cationic peptides originally isolated from B. polymyxa. They bind and kill Gram-negative bacteria. The B series of polymyxins consist of a cyclic heptapeptide and a tripeptide side chain acylated at the amino terminus by a fatty acid. Polymyxin B (sulfate) is a mixture of at least four closely related components, polymyxin B₁ to B₄, with polymyxin B₁ and B₂ being the two major components. Polymyxin B (sulfate) has rapid in vitro bactericidal activity against major multidrug-resistant Gram-negative bacteria, such as P. aeruginosa, A. baumannii, and K. pneumoniae.

Chemical properties

White Solid

The Uses of Polymyxin B sulfate

Polymyxin B sulfate is used as topical antibiotic agent, often used in combination with neomycin; products include ointments, creams, eye, and ear drops.

The Uses of Polymyxin B sulfate

antibacterial

The Uses of Polymyxin B sulfate

Antibiotic with bactericidal action on E. coli. Binds to the lipid A portion of bacterial lipopolysaccharides. Induces pore formation in the membranes of cortex cells from excised sorghum roots. Mixtu re of Polymyxin B1 and B2 sulfate. Biological potency (dry basis): >6000U/mg.

What are the applications of Application

Polymyxin B Sulfate is an antibiotic mixture active against Gram (?) organisms

Indications

Polymyxin B is one of a group of cyclic polypeptides elaborated by Bacillus polymyxa. The drug is a surface-active agent. It is thought to alter the lipoprotein membrane of bacteria so that it no longer functions as an effective barrier, thereby allowing the cell contents to escape. Polymyxin B is effective against Pseudomonas, E. coli, and other gram-negative bacteria except the Proteus and Serratia species. It has little effect on gram-positive organisms.

brand name

(GlaxoSmithKline); Poly-Rx (X Gen).

General Description

Polymyxin (Aerosporin) was discovered in 1947 almost simultaneouslyin three separate laboratories in the UnitedStates and Great Britain. As often happens whensimilar discoveries are made in widely separated laboratories,differences in nomenclature, referring to both theantibiotic-producing organism and the antibiotic itself, appearedin references to the polymyxins. Because the organismsfirst designated as Bacillus polymyxa and B.aerosporus Greer were found to be identical species, thename B. polymyxa is used to refer to all of the strains thatproduce the closely related polypeptides called polymyxins.Other organisms (e.g., see “Colistin” later) also producepolymyxins. Identified so far are polymyxins A, B1,B2, C, D1, D2, M, colistin A (polymyxin E1), colistin B(polymyxin E2), circulins A and B, and polypeptin. Theknown structures of this group and their properties havebeen reviewed by Vogler and Studer. Of these,polymyxin B as the sulfate usually is used in medicine because,when used systemically, it causes less kidney damagethan the others. Polymyxin B sulfate is a nearly odorless, white to buff powder. It is freely soluble in water and slightly soluble in alcohol.

Biochem/physiol Actions

Polymyxin B?is one of the most important antibiotics used to treat gram-negative bacterial infections, including infections caused by carbapenem-resistant non-fermenters and carbapenem-resistant?Enterobacteriaceae.

Clinical Use

Polymyxin B is produced by fermentation of Bacillus polymyxa. It is separated from a mixture of related cyclic peptides and is primarily active against Gram-negative microorganisms. It apparently binds to phosphate groups in bacterial cytoplasmic membranes and disrupts their integrity. It is used IM or IV as a sulfate salt to treat serious urinary tract infections, meningitis, and septicemia, primarily caused by Pseudomonas aeruginosa, but some other Gram-negative bacteria also will respond. Irrigation of the urinary bladder with solutions of polymyxin B sulfate is employed as well by some to reduce the incidence of infections subsequent to installation of indwelling catheters. Additionally, it is used ophthalmically to treat infections by P. aeruginosa. When given parenterally, the drug is neuro- and nephrotoxic and, therefore, is employed only after other drugs have failed.

in vitro

polymyxin b elicited up-regulation of dendritic cells (dcs) maturation markers, including the increase in the in the expression of co-stimulatory molecule cd86 and hla-class i and ii molecules. polymyxin b induced a progressive increase in the adhesion property of human dcs. in addition, polymyxin b triggered the activation of the erk1/2 pathway and iκb-α/nf-κb pathways [1].

in vivo

male bacteraemia ddy mice were subcutaneously treated with polymyxin b at a dose of 5, 10, 15 or 20 mg/kg for 7 days. polymyxin b, in a dose-dependent fashion, improved the survival both of ou-01062- and ou-98039-infected mice. in polymyxin b-treated mice, except for 5 mg/kg polymyxin b, the viable cell counts had a tendency to reduce steadily in each concentration group. it was showed a rapid and marked decline of bacterial cell count between 3 to 6 h after infection [2].

storage

Room temperature

References

[1]. valentinis, b., bianchi, a., zhou, d., cipponi, a., catalanotti, f., russo, v., & traversari, c. direct effects of polymyxin b on human dendritic cells maturation: the role of i b- /nf- b and erk1/2 pathways and adhesion. journal of biological chemistry. 2005; 280(14): 14264-14271.
[2]. miyajima, y., hiramatsu, k., mizukami, e., morinaga, r., ishii, h., & shirai, r. et al. in vitro and in vivo potency of polymyxin b against imp-type metallo-β-lactamase-producing pseudomonas aeruginosa. international journal of antimicrobial agents. 2008; 32(5): 437-440.