Polymyxin B (sulfate)

A cationic peptide antibiotic

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Background

Polymyxin B, a mixture of polymyxins B1 and B2, is obtained from Bacillus polymyxa strains. Polymyxin B exhibits bactericidal activity against major multidrug-resistant gram-negative bacteria, most fungi and gram-positive bacteria. As basic polypeptides of about eight amino acids, polymyxins B1 and B2 have cationic detergent action on cell membranes. Moreover, polymyxin B is used for infections with gram-negative organisms, which may be nephrotoxic and neurotoxic. Polymyxin B is appropriate to treat the infections of the meninges, urinary tract, and blood stream, triggered by susceptible Pseudomonas aeruginosa strains.

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].

多粘菌素B是由多粘菌属菌株产生的多肽混合物，包括多粘菌B1和B2。多粘菌素B对主要的多重耐药革兰阴性细菌、大多数真菌和革兰阳性细菌具有杀菌作用。作为由约八个氨基酸组成的碱性多肽，多粘菌素B具有对细胞膜的阳离子表面活性剂作用。此外，多粘菌素B可用于治疗由易感性铜绿假单胞菌菌株引起的脑膜炎、泌尿道感染和血液感染等革兰阴性菌感染。

体外：多粘菌素B可诱导树突状细胞成熟标志物的上调，包括共刺激分子CD86和HLA-I和II分子的表达增加。多粘菌素B可逐渐增强人类树突状细胞的粘附性质，并激活ERK1/2途径和IκB-α/NF-κB途径[1]。

体内：雄性败血症ddY小鼠皮下注射多粘菌素B，剂量为5、10、15或20 mg/kg，治疗7天。多粘菌素B以剂量依赖的方式改善了OU-01062和OU-98039感染小鼠的生存率。在多粘菌素B治疗的小鼠中，除了5 mg/kg的多粘菌素B外，每个浓度组的活细胞计数均趋于稳步降低。感染后3到6小时内细菌细胞数显著下降[2]。

参考文献:
[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.