Bacitracin: Difference between revisions

{{Short description|Polypeptide antibiotic}}

{{Use dmy dates|date=January 2024}}

{{cs1 config |name-list-style=vanc |display-authors=6}}

| verifiedrevid = 457285800

| image2 = Bacitracin ball-and-stick.png

<!-- Clinical data -->

| tradename = Baciguent, Baciim, others

| pregnancy_AUえーゆー = D

| routes_of_administration = [[Topical]], [[Intramuscular injection|intramuscular]], [[Ophthalmic drug administration]]

| ATC_prefix = D06

| ATC_suffix = AX05

| ATC_supplemental = {{ATC|J01|XX10}}, {{ATC|R02|AB04}}, {{ATC|S01|AA32}}, {{ATCvet|A07|AA93}}

| legal_AUえーゆー = S4

| legal_US = OTC

| legal_US_comment = /&nbsp;Rx-only

| elimination_half-life =

| ChEBI = 28669

| KEGG = D00128

| ChEMBL_Ref = {{ebicite|changed|EBI}}

| ChEMBL = 1200558

<!--Chemical data-->

| IUPAC_name = (4''R'')-4-[(2''S'')-2-({2-[(1''S'')-1-amino-2-methylbutyl]- 4,5-dihydro-1,3-thiazol-5-yl}formamido)-4-methylpentanamido]-4-<nowiki/>{[(1''S'')- 1-<nowiki/>{[(3''S'',6''R'',9''S'',12''R'',15''S'',18''R'',21''S'')- 18-(3-aminopropyl)-12-benzyl-15-(butan-2-yl)-3-(carbamoylmethyl)- 6-(carboxymethyl)-9-(1''H''-imidazol-5-ylmethyl)-2,5,8,11,14,17,20- heptaoxo-1,4,7,10,13,16,19-heptaazacyclopentacosan-21-yl]carbamoyl}- 2-methylbutyl]carbamoyl}butanoic acid

| C=66 | H=103

| N=17 | O=16

| S=1

| smiles = CCC(C)C(N)NC4=NC(C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@@H](C(C)CC)C(=O)N[C@H]3CCCCNC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](CC(O)=O)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](C(C)CC)NC(=O)[C@@H](CCCN)NC3=O)CS4

'''Bacitracin'''<ref>{{cite book| vauthors = Elks J, Ganellin CR |title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|date=1990|publisher=Springer|isbn=978-1-4757-2085-3|pages=119–}}</ref> is a [[polypeptide antibiotic]]. It is a mixture of related [[cyclic peptides]] produced by ''[[Bacillus licheniformis]]'' bacteria, that was first isolated from the variety "Tracy I" ([[ATCC (company)|ATCC]] 10716) in 1945.<ref>Originally grouped under ''B. subtilis'', but nomenclature has since changed. See {{cite web | vauthors = Podstawka A |title=Bacillus licheniformis Tracy I {{!}} DSM 603, ATCC 10716, CCM 2181, IFO 12199, NBRC 12199, NCIB 8874, FDA BT1 {{!}} BacDiveID:686 |url=https://bacdive.dsmz.de/strain/686 |website=bacdive.dsmz.de |language=en |access-date=7 February 2022 |archive-date=7 February 2022 |archive-url=https://web.archive.org/web/20220207144504/https://bacdive.dsmz.de/strain/686 |url-status=live }}</ref> These peptides disrupt [[Gram-positive bacteria]] by interfering with [[cell wall]] and [[Peptidoglycan#Biosynthesis|peptidoglycan synthesis]].

Bacitracin is primarily used as a topical preparation, as it can cause kidney damage when used internally.<ref name="Zintel">{{cite journal | vauthors = Zintel HA, Ma RA | title = The absorption, distribution, excretion and toxicity of bacitracin in man | journal = The American Journal of the Medical Sciences | volume = 218 | issue = 4 | pages = 439–445 | date = October 1949 | pmid = 18140540 | doi = 10.1097/00000441-194910000-00012 | s2cid = 2371497 }}</ref> It is generally safe when used topically, but in rare cases may cause [[hypersensitivity]], [[allergy|allergic]] or [[anaphylaxis|anaphylactic]] reactions, especially in people allergic to [[neomycin]].<ref>{{cite journal | vauthors = Spann CT, Taylor SC, Weinberg JM | title = Topical antimicrobial agents in dermatology | journal = Disease-a-Month | volume = 50 | issue = 7 | pages = 407–421 | date = July 2004 | pmid = 15280871 | doi = 10.1016/j.disamonth.2004.05.011 }}</ref><ref>{{cite journal | vauthors = Trookman NS, Rizer RL, Weber T | title = Treatment of minor wounds from dermatologic procedures: a comparison of three topical wound care ointments using a laser wound model | journal = Journal of the American Academy of Dermatology | volume = 64 | issue = 3 Suppl | pages = S8-15 | date = March 2011 | pmid = 21247665 | doi = 10.1016/j.jaad.2010.11.011 | doi-access = free }}</ref>

In 2021, it was the 300th most commonly prescribed medication in the United States, with more than 400,000 prescriptions.<ref>{{cite web | title=The Top 300 of 2021 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=14 January 2024 | archive-date=15 January 2024 | archive-url=https://web.archive.org/web/20240115223848/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Bacitracin - Drug Usage Statistics | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Bacitracin | access-date = 14 January 2024}}</ref>

== Medical uses ==

[[Image:Bacitracin ointment.jpg|thumb|left|A tube of bacitracin ointment for eyes]] Bacitracin is used in human medicine as a [[polypeptide antibiotic]] and is "approved by the US [[Food and Drug Administration]] (FDA) for use in chickens and turkeys," though use in animals contributes to [[antibiotic resistance]].<ref name="disc">{{cite web | vauthors = Pearl MC | date = 12 September 2007 | url = http://discovermagazine.com/2007/sep/better-planet | title = Antibiotic use on the farm hurts people—and doesn't help the bottom line. | work = [[Discover Magazine]] | archive-url = https://web.archive.org/web/20070925063617/http://discovermagazine.com/2007/sep/better-planet | archive-date = 25 September 2007 }}</ref>

As bacitracin zinc salt, in combination with other topical antibiotics (usually [[polymyxin B]] and [[neomycin]]) as an [[ointment]] ("triple antibiotic ointment," with the brand name [[Neosporin]]), it is used for topical treatment of a variety of localized skin and eye infections, as well as for the prevention of wound [[infection]]s. A non-ointment form of ophthalmic solution is also available for eye infections.<ref>{{cite web|url=http://www.healthgrades.com/drug-ratings/drug/information/1246/Triple%20Antibiotic|title=Healthgrades > Find a Doctor > Doctor Reviews > Hospital Ratings|url-status=dead|archive-url=https://web.archive.org/web/20110523141000/http://www.healthgrades.com/drug-ratings/drug/information/1246/Triple%20Antibiotic|archive-date=23 May 2011}}</ref>

[[image:3D Aminated Chem Struct Bacitracin A.gif|thumb|200px|3D Chemical Structure of Bacitracin]]

=== Spectrum of activity and susceptibility data ===

Bacitracin is a narrow-spectrum antibiotic. It targets Gram-positive bacteria, especially those that cause skin infections. The following represents susceptibility data for a few medically significant microorganisms.<ref>{{cite web | title = Bacitracin Susceptibility and Minimum Inhibitory Concentration (MIC) Data | url = http://www.toku-e.com/Assets/MIC/Bacitracin.pdf | work = TOKU-E | access-date = 12 August 2013 | archive-date = 22 December 2018 | archive-url = https://web.archive.org/web/20181222141944/http://www.toku-e.com/Assets/MIC/Bacitracin.pdf | url-status = live }}</ref>

* ''[[Staphylococcus aureus]]'' – ≤0.03 μみゅーg/mL – 700 μみゅーg/mL

* ''[[Staphylococcus epidermidis]]'' – 0.25 μみゅーg/mL – >16 μみゅーg/mL

* ''[[Streptococcus pyogenes]]'' – 0.5 μみゅーg/mL – >16 μみゅーg/mL

== Mechanism of action ==

Bacitracin interferes with the dephosphorylation of [[C55-isoprenyl pyrophosphate|C₅₅-isoprenyl pyrophosphate]], and a related molecule known as [[bactoprenol]] pyrophosphate; both of these lipids function as membrane carrier molecules that transport the building-blocks of the [[peptidoglycan]] bacterial [[cell wall]] outside of the inner membrane.<ref name="pmid4332017">{{cite journal | vauthors = Stone KJ, Strominger JL | title = Mechanism of action of bacitracin: complexation with metal ion and C 55 -isoprenyl pyrophosphate | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 68 | issue = 12 | pages = 3223–7 | date = December 1971 | pmid = 4332017 | pmc = 389626 | doi = 10.1073/pnas.68.12.3223 | bibcode = 1971PNAS...68.3223S | doi-access = free | title-link = doi }}</ref>

== History ==

Bacitracin was isolated by [[Balbina Johnson]], a [[bacteriologist]] at the [[Columbia University College of Physicians and Surgeons]].<ref name="pmid17770204"/> Its name derives from the fact that a compound produced by a microbe in young Margaret Tracy's (1936–1994)<ref>{{cite web |url=https://files.nyu.edu/jmm257/public/other/bacitracin.html |title=Margaret Tracy & Balbina Johnson: The Women Behind Bacitracin |access-date=30 September 2014 |url-status=dead |archive-url= https://web.archive.org/web/20140428190211/https://files.nyu.edu/jmm257/public/other/bacitracin.html |archive-date=28 April 2014 }}</ref> leg injury showed antibacterial activity.<ref>{{Cite web|url=https://healthmatters.nyp.org/bacitracin-discovery/|title=NewYork-Presbyterian &#124; the Discovery of Bacitracin|date=7 February 2017|access-date=9 April 2020|archive-date=27 February 2021|archive-url=https://web.archive.org/web/20210227164020/https://healthmatters.nyp.org/bacitracin-discovery/|url-status=live}}</ref>

<blockquote>''One strain isolated from tissue debrided from a compound fracture of the tibia was particularly active. We named this growth-antagonistic strain for the patient, "Tracy I." When cell-free filtrates of broth cultures of this bacillus proved to possess strong antibiotic activity and to be non-toxic, further study seemed warranted. We have called this active principle "Bacitracin.''<ref name="pmid17770204">{{cite journal | vauthors = Johnson BA, Anker H, Meleney FL | title = Bacitracin: a new antibiotic produced by a member of the B. subtilis group | journal = Science | volume = 102 | issue = 2650 | pages = 376–7 | date = October 1945 | pmid = 17770204 | doi = 10.1126/science.102.2650.376 | bibcode = 1945Sci...102..376J | s2cid = 51066 }}</ref></blockquote>

Bacitracin was approved by the US FDA in 1948.<ref>{{Cite web|title=Drugs@FDA: FDA-Approved Drugs|url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=060733|access-date=17 September 2021|website=U.S. [[Food and Drug Administration]] (FDA)|archive-date=27 July 2021|archive-url=https://web.archive.org/web/20210727171910/https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=060733|url-status=dead}}</ref>

== Synthesis ==

Bacitracin is synthesised via [[nonribosomal peptide synthetase]]s (NRPSs), which means that [[ribosome]]s are not directly involved in its [[nonribosomal peptide|synthesis]]. The three-enzyme [[operon]] is called BacABC, not to be confused with BacABCDE of [[bacilycin]] synthesis.<ref>{{cite journal | vauthors = Konz D, Klens A, Schörgendorfer K, Marahiel MA | title = The bacitracin biosynthesis operon of Bacillus licheniformis ATCC 10716: molecular characterization of three multi-modular peptide synthetases | journal = Chemistry & Biology | volume = 4 | issue = 12 | pages = 927–937 | date = December 1997 | pmid = 9427658 | doi = 10.1016/s1074-5521(97)90301-x | title-link = doi | doi-access = free }}</ref>

== Composition ==

Bacitracin is composed of a mixture of related compounds with varying degrees of antibacterial activity. Notable fractions include bacitracin A, A1, B, B1, B2, C, D, E, F, G, and X.<ref>"Committee for Veterinary Medicinal Products Bacitracin." Ema.europa.eu. The European Agency for the Evaluation of Medicinal Products, June 1998. Web. 18 January 2013</ref> Bacitracin A has been found to have the most antibacterial activity. Bacitracin B1 and B2 have similar potencies and are approximately 90% as active as bacitracin A.<ref name="pmid1601975">{{cite journal | vauthors = Bell RG | title = Preparative high-performance liquid chromatographic separation and isolation of bacitracin components and their relationship to microbiological activity | journal = Journal of Chromatography | volume = 590 | issue = 1 | pages = 163–8 | date = January 1992 | pmid = 1601975 | doi = 10.1016/0021-9673(92)87018-4 | doi-access = free }}</ref>

== Society and culture ==

=== Controversies ===

Claims that bacitracin is a [[protein disulfide isomerase]] inhibitor are disputed by ''in vitro'' studies.<ref>{{cite journal | vauthors = Karala AR, Ruddock LW | title = Bacitracin is not a specific inhibitor of protein disulfide isomerase | journal = The FEBS Journal | volume = 277 | issue = 11 | pages = 2454–62 | date = June 2010 | pmid = 20477872 | doi = 10.1111/j.1742-4658.2010.07660.x | s2cid = 37519169 }}</ref><ref>{{cite journal | vauthors = Weston BS, Wahab NA, Roberts T, Mason RM | title = Bacitracin inhibits fibronectin matrix assembly by mesangial cells in high glucose | journal = Kidney International | volume = 60 | issue = 5 | pages = 1756–64 | date = November 2001 | pmid = 11703593 | doi = 10.1046/j.1523-1755.2001.00991.x | doi-access = free | title-link = doi }}</ref>

== References ==

{{Reflist}}

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[[Category:Cyclic peptides]]