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{{Short description|Antibiotic medication}} |
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{{Refimprove|date=June 2010}} |
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{{Infobox drug |
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| verifiedrevid = 414279035 |
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| IUPAC_name = <nowiki>N-amino]butan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxobutan-2-yl]-6-methyloctanamide</nowiki> |
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| image = Polymyxin B1.svg |
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| image2 = polymyxin B2.svg |
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<!--Clinical data--> |
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{{drugbox |
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| tradename = Poly-Rx, others |
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| IUPAC_name = <nowiki>N-[4-amino-1-[[1-[[4-amino-1-oxo-1-[[6,9,18-tris |
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| Drugs.com = {{drugs.com|monograph|polymyxin-b-sulfate-topical}} |
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(2-aminoethyl)-15-benzyl-3-(1-hydroxyethyl)-12- |
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| pregnancy_category = B<ref name=AHFS2019/> |
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(2-methylpropyl)-2,5,8,11,14,17,20- |
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| legal_status = OTC |
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heptaoxo-1,4,7,10,13,16,19-heptazacyclotricos-21-yl] |
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| routes_of_administration = ], ], ], ], eye drops |
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amino]butan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl] |
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amino]-1-oxobutan-2-yl]-6-methyloctanamide</nowiki> |
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<!--Pharmacokinetic data--> |
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| image = Polymyxin B Sulfate.png |
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| bioavailability = |
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| protein_bound = |
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| metabolism = |
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<!--Identifiers--> |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number = 1405-20-5 |
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| CAS_number = 1405-20-5 |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII = 19371312D4 |
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| ATC_prefix = A07 |
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| ATC_prefix = A07 |
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| ATC_suffix = AA05 |
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| ATC_suffix = AA05 |
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| ATC_supplemental = {{ATC|J01|XB02}} {{ATC|S01|AA18}} {{ATC|S02|AA11}} {{ATC|S03|AA03}} {{ATCvet|J51|XB02}} |
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| ATC_supplemental = {{ATC|J01|XB02}} {{ATC|S01|AA18}} {{ATC|S02|AA11}} {{ATC|S03|AA03}} {{ATCvet|J51|XB02}} |
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| PubChem = 5702105 |
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| PubChem = 5702105 |
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| NIAID_ChemDB = 007797 |
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| DrugBank = APRD01190 |
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| DrugBank_Ref = {{drugbankcite|changed|drugbank}} |
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| DrugBank = DB00781 |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| ChEMBL = 1201283 |
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<!--Chemical data--> |
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| C=56 | H=100 | N=16 | O=17 | S=1 |
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| C=56 | H=100 | N=16 | O=17 | S=1 |
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| molecular_weight = 1301.56 g/mol |
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| bioavailability = |
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| pregnancy_category = |
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| legal_status = |
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| routes_of_administration = ] |
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}} |
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}} |
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<!-- Definition and medical sues --> |
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'''Polymyxin B''', sold under the brand name '''Poly-Rx''' among others, is an ] used to treat ], ], ], and ].<ref name=AHFS2019>{{cite web |title=Polymyxin B Sulfate topical Monograph for Professionals |url=https://www.drugs.com/monograph/polymyxin-b-sulfate-topical.html |website=Drugs.com |access-date=11 November 2019 |language=en}}</ref> While it is useful for many ] infections, it is not useful for ] infections.<ref name=AHFS2019/> It can be given by ], ], or ] or ].<ref name=AHFS2019/> The injectable form is generally only used if other options are not available.<ref name=Ben2009/> It is also available as the combinations ] and ] for use on the skin.<ref name="Triple2019">{{cite web |title=Neomycin, bacitracin, polymyxin b ointment |url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=26c6ab3e-f4a7-48ea-8b83-fef9d1290638 |access-date=19 April 2019 |work=DailyMed |publisher=U.S. National Library of Medicine}}</ref><ref name=Woo2015>{{cite book | vauthors = Woo TM, Robinson MV |title=Pharmacotherapeutics For Advanced Practice Nurse Prescribers |date=2015 |publisher=F.A. Davis |isbn=9780803645813 |page=651 |url=https://books.google.com/books?id=2Q5hCgAAQBAJ&q=%2B%22most+providers+are+recommending+that+patients+use+double-antibiotic+%28Polysporin%29+rather+than+triple-antibiotic+%28Neomycin%29+products%22&pg=PA651 |language=en}}</ref> |
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<!-- Side effects and mechanism --> |
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Common side effects when given by injection include ], neurological problems, fever, itchiness, and rash.<ref name=AHFS2019/> Injections into muscle may result in significant pain.<ref name=AHFS2019/> Other serious side effects may include ], ], and muscle weakness.<ref name=AHFS2019/> It is unclear if use during ] is safe for the baby.<ref name=AHFS2019/> Polymyxin B works by breaking down the ] which generally results in ].<ref name=AHFS2019/> |
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<!-- History and culture --> |
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Polymyxin B was approved for medical use in the United States in 1964.<ref name=AHFS2019/> It is on the ].<ref name="WHO21st">{{cite web |title=World Health Organization model list of essential medicines: 21st list 2019 |date=2019|hdl=10665/325771 | publisher = World Health Organization | url = https://apps.who.int/iris/bitstream/handle/10665/325771/WHO-MVP-EMP-IAU-2019.06-eng.pdf |last1=Organization |first1=World Health }}</ref> It is available as a ].<ref name=AHFS2019/> In the European Union it is only approved to be applied to the skin as of 2015.<ref>{{cite web |title=Polymyxin-based products | work = Assessment report |url=https://www.ema.europa.eu/en/documents/referral/assessment-report-article-53-procedure-polymyxin-based-products_en.pdf | publisher = European Medicines Agency |access-date=11 November 2019}}</ref> It is derived from the bacterium '']'' (formerly known as '']'').<ref name=Ben2009>{{cite book | vauthors = Bennett JE, Dolin R, Blaser MJ, Mandell GL |title=Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases E-Book |date=2009 |publisher=Elsevier Health Sciences |isbn=9781437720600 |page=469 |url=https://books.google.com/books?id=uPbHJdSGjPEC&pg=PA469 }}</ref> In 2022, the combination of polymyxin B with ] and ] was the 274th most commonly prescribed medication in the United States, with more than 800,000 prescriptions.<ref>{{cite web | title=The Top 300 of 2022 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=30 August 2024 | archive-date=30 August 2024 | archive-url=https://web.archive.org/web/20240830202410/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Dexamethasone; Neomycin; Polymyxin B Drug Usage Statistics, United States, 2013 - 2022 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/DexamethasoneNeomycinPolymyxinB | access-date = 30 August 2024 }}</ref> |
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==Medical uses== |
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===Spectrum of susceptibility=== |
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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. |
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* ''Haemophilus influenzae'': ≥0.8 μg/mL |
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* ''Pseudomonas aeruginosa'': 0.25–1 μg/mL<ref>{{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}}</ref> |
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=== Endotoxin adsorption === |
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{{anchor|Toraymyxin}} |
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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.<ref>{{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 }}</ref> |
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== Mechanism of action == |
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#Alters ] 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 ] portion <ref>{{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 }}</ref> (this site normally is a binding site for calcium and magnesium counter ions); the result is a destabilized outer membrane |
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#Fatty acid portion dissolves in hydrophobic region of ] and disrupts membrane integrity |
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#Leakage of cellular molecules, inhibition of cellular respiration |
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#Binds and inactivates ]<ref name="pmid17201926">{{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 }}</ref> |
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#Relative absence of selective toxicity: nonspecific for cell membranes of any type, highly toxic. |
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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.<ref>{{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 }}</ref> |
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'''Polymyxin B''' is an antibiotic primarily used for resistant ] infections. It is derived from the bacterium Bacillus polymyxa. Polymyxin B sulfate has a bactericidal action against almost all gram-negative bacilli except the ] group. Polymyxins bind to the cell membrane and alter its structure, making it more permeable. The resulting water uptake leads to cell death. They are cationic, basic proteins that act like detergents (]s). Side-effects include neurotoxicity and acute renal tubular necrosis. It is commonly used in the topical first-aid preparation ]. |
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== Mixture composition == |
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# Family of polypeptides with attached fatty acid; ] ] at physiological pH, both hydrophilic and hydrophobic properties |
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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.<ref>{{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 }}</ref> |
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# Bactericidal for ]; little to no effect on ], since cell wall is too thick to permit access to membrane |
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== Research application == |
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==Mechanism of action== |
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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 ] (sRNA) responses in ''Salmonella enterica''.<ref>{{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 }}</ref> |
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# Alters ] 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 (this site normally is a binding site for calcium and magnesium counter ions); the result is a destabilized outer membrane |
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# Fatty acid portion dissolves in hydrophobic region of ] and disrupts membrane integrity |
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# Leakage of cellular molecules, inhibition of cellular respiration |
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# Binds and inactivates endotoxin<ref name="pmid17201926">{{cite journal |author=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=Microb. Cell Fact. |volume=6 |issue= |pages=1 |year=2007 |pmid=17201926 |pmc=1766364 |doi=10.1186/1475-2859-6-1 |url=http://www.microbialcellfactories.com/content/6//1}}</ref> |
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# Relative absence of selective toxicity: nonspecific for cell membranes of any type, highly toxic |
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==Research application== |
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== See also == |
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* ] |
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# In addition to its antibiotic function, polymix B has been used to clear endotoxin contamination in reagents. |
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* ] |
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==References== |
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== References == |
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{{reflist}} |
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{{Reflist}} |
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{{Other antibacterials}} |
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{{Cell wall disruptive antibiotics |Other}} |
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{{Antidiarrheals, intestinal anti-inflammatory/anti-infective agents}} |
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{{Antidiarrheals, intestinal anti-inflammatory/anti-infective agents}} |
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{{Otologicals}} |
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{{Otologicals}} |
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