Common side effects when given by injection includekidney problems, neurological problems, fever, itchiness, and rash.[1] Injections into muscle may result in significant pain.[1] Other serious side effects may includefungal infections,anaphylaxis, and muscle weakness.[1] It is unclear if use duringpregnancy is safe for the baby.[1] Polymyxin B works by breaking down thecytoplasmic membrane which generally results inbacterial cell death.[1]
Polymyxin B has been used to treat urinary tract infections and meningitis caused byPseudomonas aeruginosa andHaemophilus influenzae, respectively. The following represents MIC susceptibility data for a few medically significant microorganisms.
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.[10]
Altersbacterial 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 thecyclic peptide portion[11] (this site normally is a binding site for calcium and magnesium counter ions); the result is a destabilized outer membrane
Fatty acid portion dissolves in hydrophobic region ofcytoplasmic membrane and disrupts membrane integrity
Leakage of cellular molecules, inhibition of cellular respiration
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.[13]
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.[14]
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 ofsmall RNA (sRNA) responses inSalmonella enterica.[15]
^Shoji H (February 2003). "Extracorporeal endotoxin removal for the treatment of sepsis: endotoxin adsorption cartridge (Toraymyxin)".Therapeutic Apheresis and Dialysis.7 (1):108–114.doi:10.1046/j.1526-0968.2003.00005.x.PMID12921125.S2CID41911308.
^Tsubery H, Ofek I, Cohen S, Fridkin M (2000-01-01). "Structure activity relationship study of polymyxin B nonapeptide".The Biology and Pathology of Innate Immunity Mechanisms. Advances in Experimental Medicine and Biology. Vol. 479. pp. 219–222.doi:10.1007/0-306-46831-X_18.ISBN978-0-306-46409-6.PMID10897422.
^Orwa JA, Govaerts C, Busson R, Roets E, Van Schepdael A, Hoogmartens J (April 2001). "Isolation and structural characterization of polymyxin B components".Journal of Chromatography A.912 (2):369–373.doi:10.1016/S0021-9673(01)00585-4.PMID11330807.
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