polymyxin B

Polymyxin B has been used to treat urinary tract infections and meningitis caused by Pseudomonas aeruginosa and Haemophilus influenzae, respectively. The following represents MIC susceptibility data for a few medically significant microorganisms.

• Haemophilus influenzae: ≥0.8 μg/mL
• Pseudomonas aeruginosa: 0.25–1 μg/mL{{cite web|url=http://www.toku-e.com/Assets/MIC/Polymyxin%20B%20sulfate.pdf |title=Polymyxin B sulfate : Susceptibility and Minimum Inhibitory Concentration (MIC) Data |website=Toku-e.com |access-date=2017-04-02}}

{{anchor|Toraymyxin}}

An effective use of polymyxin B is found in patients with refractory septic shock, that is, without positive outcome to the administration of standard treatments (increase in volemia and other antibiotics). The obstacle of the toxicity of polymyxin B is bypassed by extracorporeal circulation with perfusion of venous blood through a cartridge on whose fibers polymyxin B is covalently fixed; in this way the antibiotic exerts its bactericidal function but is not released into the blood since it remains fully attached to the fiber. Through this perfusion the cartridge retains the endotoxin, recognized as the trigger of septic shock. The treatment of the cartridge to polymyxin B (Toraymyxin, medical device designed and produced by the Japanese Toray), takes place in two sessions of two hours each, carried out at a distance of 24 hours.{{cite journal | vauthors = Shoji H | title = Extracorporeal endotoxin removal for the treatment of sepsis: endotoxin adsorption cartridge (Toraymyxin) | journal = Therapeutic Apheresis and Dialysis | volume = 7 | issue = 1 | pages = 108–114 | date = February 2003 | pmid = 12921125 | doi = 10.1046/j.1526-0968.2003.00005.x | s2cid = 41911308 }}

1. Alters bacterial outer membrane permeability by binding to a negatively charged site in the lipopolysaccharide layer, which has an electrostatic attraction for the positively charged amino groups in the cyclic peptide portion {{cite journal | vauthors = Khondker A, Dhaliwal AK, Saem S, Mahmood A, Fradin C, Moran-Mirabal J, Rheinstädter MC | title = Membrane charge and lipid packing determine polymyxin-induced membrane damage | journal = Communications Biology | volume = 2 | pages = 67 | date = February 2019 | pmid = 30793045 | pmc = 6379423 | doi = 10.1038/s42003-019-0297-6 }} (this site normally is a binding site for calcium and magnesium counter ions); the result is a destabilized outer membrane
2. Fatty acid portion dissolves in hydrophobic region of cytoplasmic membrane and disrupts membrane integrity
3. Leakage of cellular molecules, inhibition of cellular respiration
4. Binds and inactivates endotoxin{{cite journal | vauthors = Cardoso LS, Araujo MI, Góes AM, Pacífico LG, Oliveira RR, Oliveira SC | title = Polymyxin B as inhibitor of LPS contamination of Schistosoma mansoni recombinant proteins in human cytokine analysis | journal = Microbial Cell Factories | volume = 6 | pages = 1 | date = January 2007 | pmid = 17201926 | pmc = 1766364 | doi = 10.1186/1475-2859-6-1 | doi-access = free }}
5. Relative absence of selective toxicity: nonspecific for cell membranes of any type, highly toxic.

Removal of the hydrophobic tail of polymyxin B yields polymyxin nonapeptide (PMBN), which still binds to LPS, but no longer kills the bacterial cell. However, it still detectably increases the permeability of the bacterial cell wall to other antibiotics, indicating that it still causes some degree of membrane disorganization.{{cite book | vauthors = Tsubery H, Ofek I, Cohen S, Fridkin M | title = The Biology and Pathology of Innate Immunity Mechanisms | chapter = Structure activity relationship study of polymyxin B nonapeptide | series = Advances in Experimental Medicine and Biology | volume = 479 | pages = 219–222 | date = 2000-01-01 | pmid = 10897422 | doi = 10.1007/0-306-46831-X_18 | isbn = 978-0-306-46409-6 }}

Polymyxin B is composed of polymyxins B1, B1-I, B2, B3, and B6. Polymyxins B1 and B2 are considered major components. These related components are structurally identical with the exception of a variable fatty acid group on each fraction. Results from in vitro studies have shown marginal differences in MIC data when comparing the fractions.{{cite journal | vauthors = Orwa JA, Govaerts C, Busson R, Roets E, Van Schepdael A, Hoogmartens J | title = Isolation and structural characterization of polymyxin B components | journal = Journal of Chromatography A | volume = 912 | issue = 2 | pages = 369–373 | date = April 2001 | pmid = 11330807 | doi = 10.1016/S0021-9673(01)00585-4 }}

Polymyxin B is also used to induce envelope stress in order to study the organisms response to such stress. Polymyxin envelope stress assays such as this have been used for the study of small RNA (sRNA) responses in Salmonella enterica.{{cite journal | vauthors = Hébrard M, Kröger C, Srikumar S, Colgan A, Händler K, Hinton JC | title = sRNAs and the virulence of Salmonella enterica serovar Typhimurium | journal = RNA Biology | volume = 9 | issue = 4 | pages = 437–445 | date = April 2012 | pmid = 22546935 | pmc = 3384567 | doi = 10.4161/rna.20480 }}

• Polymyxin
• SPR741

{{Reflist}}

{{Other antibacterials}}

{{Antidiarrheals, intestinal anti-inflammatory/anti-infective agents}}

{{Otologicals}}

Category:Polymyxin antibiotics

Category:Otologicals

Category:Cyclic peptides

Category:Polypeptide antibiotics

Category:World Health Organization essential medicines

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