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{{Short description|Polypeptide Antibiotic (Gram Positive Bacteriacide)}}
{{Short description|Polypeptide antibiotic}}
{{Use dmy dates|date=January 2024}}
{{cs1 config |name-list-style=vanc |display-authors=6}}
{{Drugbox
{{Drugbox
| Verifiedfields = changed
| Verifiedfields = changed
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| image = Bacitracin A.svg
| image = Bacitracin A.svg
| image2 = Bacitracin ball-and-stick.png
| image2 = Bacitracin ball-and-stick.png

<!-- Clinical data -->
<!-- Clinical data -->
| tradename = Baciguent, Baciim, others
| tradename = Baciguent, Baciim, others
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| ATC_prefix = D06
| ATC_prefix = D06
| ATC_suffix = AX05
| ATC_suffix = AX05
| ATC_supplemental = {{ATC|J01|XX10}} {{ATC|R02|AB04}} {{ATCvet|A07|AA93}} <!-- scheduled to be S01AA32 in 2024 -->
| ATC_supplemental = {{ATC|J01|XX10}}, {{ATC|R02|AB04}}, {{ATC|S01|AA32}}, {{ATCvet|A07|AA93}}


| legal_AU = S4
| legal_AU = S4
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| metabolism =
| metabolism =
| elimination_half-life =
| elimination_half-life =

<!--Identifiers-->
<!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number_Ref = {{cascite|correct|??}}
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| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 1200558
| ChEMBL = 1200558

<!--Chemical data-->
<!--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
| 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
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}}
}}


'''Bacitracin'''<ref>{{cite book| author1 = J. Elks | author2 = C. R. Ganellin |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 |last1=Podstawka |first1=Adam |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=2022-02-07 |archive-date=2022-02-07 |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 synthesis.
'''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 2022, it was the 323rd most commonly prescribed medication in the United States, with more than 100,000 prescriptions.<ref>{{cite web | title = Bacitracin Drug Usage Statistics, United States, 2013 - 2022 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Bacitracin | access-date = 30 August 2024 }}</ref>
⚫
Bacitracin is primarily used as a topical preparation, as it can cause kidney damage when used internally.<ref name="Zintel">{{cite journal |last1=Zintel |first1=H. A. |last2=Ma |first2=R. A. |last3=Nichols |first3=Anna C. |last4=Ellis |first4=Helen |title=The Absorption, Distribution, Excretion and Toxicity of Bacitracin in Man. |journal=American Journal of the Medical Sciences |date=1949 |volume=218 |issue=4 |pages=439–445|doi=10.1097/00000441-194910000-00012 |pmid=18140540 |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 = 407–21 | 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 }}</ref>


== Medical uses ==
== 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 | first = Mary C. | last = Pearl | name-list-style = vanc | 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 = 2007-09-25 }}</ref>
[[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=2011-05-23}}</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]]
[[image:3D Aminated Chem Struct Bacitracin A.gif|thumb|200px|3D Chemical Structure of Bacitracin]]


=== Spectrum of activity and susceptibility data ===
=== 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 = 2013-08-12 | archive-date = 2018-12-22 | archive-url = https://web.archive.org/web/20181222141944/http://www.toku-e.com/Assets/MIC/Bacitracin.pdf | url-status = live }}</ref>
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 μg/mL – 700 μg/mL
* ''[[Staphylococcus aureus]]'' – ≤0.03 μg/mL – 700 μg/mL
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== History ==
== 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 Treacy'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=2014-09-30 |url-status=dead |archive-url= https://web.archive.org/web/20140428190211/https://files.nyu.edu/jmm257/public/other/bacitracin.html |archive-date=2014-04-28 }}</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>
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>
<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=2021-09-17|website=U.S. [[Food and Drug Administration]] (FDA)|archive-date=2021-07-27|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>
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 ==
== 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>
{{missing information|section|commercial strain improvement by mutagenesis: these strains themselves have names like UV-MN-HN-6; enzyme functions|date=February 2022}}
⚫
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 |last1=Konz |first1=Dirk |last2=Klens |first2=Andrea |last3=Schörgendorfer |first3=Kurt |last4=Marahiel |first4=Mohamed A. |title=The bacitracin biosynthesis operon of Bacillus licheniformis ATCC 10716: molecular characterization of three multi-modular peptide synthetases |journal=Chemistry & Biology |date=December 1997 |volume=4 |issue=12 |pages=927–937 |doi=10.1016/s1074-5521(97)90301-x|pmid=9427658 |doi-access = free | title-link = doi }}</ref>


== Composition ==
== 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 Jan. 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 }}</ref>
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 ==
== Society and culture ==
=== Controversies ===
=== Controversies ===
Some have claimed that bacitracin is a [[protein disulfide isomerase]] inhibitor, but this is 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>
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 ==
== References ==
{{Reflist}}
{{Reflist}}


{{Other antibacterials}}
{{Cell wall disruptive antibiotics}}
{{Antibiotics and chemotherapeutics for dermatological use}}
{{Antibiotics and chemotherapeutics for dermatological use}}
{{Throat preparations}}
{{Throat preparations}}
{{Portal bar | Medicine}}
{{Portal bar | Medicine}}
{{Authority control}}


[[Category:Polypeptide antibiotics]]
[[Category:Polypeptide antibiotics]]

Latest revision as of 17:49, 2 December 2024

Bacitracin
Clinical data
Trade namesBaciguent, Baciim, others
AHFS/Drugs.comMonograph
Pregnancy
category
  • AU: D
Routes of
administration		Topical, intramuscular, Ophthalmic drug administration
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • US: OTC / Rx-only
Identifiers
  • (4R)-4-[(2S)-2-({2-[(1S)-1-amino-2-methylbutyl]- 4,5-dihydro-1,3-thiazol-5-yl}formamido)-4-methylpentanamido]-4-{[(1S)- 1-{[(3S,6R,9S,12R,15S,18R,21S)- 18-(3-aminopropyl)-12-benzyl-15-(butan-2-yl)-3-(carbamoylmethyl)- 6-(carboxymethyl)-9-(1H-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
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
Chemical and physical data
FormulaC66H103N17O16S
Molar mass1422.71 g·mol−1
3D model (JSmol)
  • 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
  • InChI=1S/C66H103N17O16S/c1-9-35(6)52(69)66-81-48(32-100-66)63(97)76-43(26-34(4)5)59(93)74-42(22-23-50(85)86)58(92)83-53(36(7)10-2)64(98)75-40-20-15-16-25-71-55(89)46(29-49(68)84)78-62(96)47(30-51(87)88)79-61(95)45(28-39-31-70-33-72-39)77-60(94)44(27-38-18-13-12-14-19-38)80-65(99)54(37(8)11-3)82-57(91)41(21-17-24-67)73-56(40)90/h12-14,18-19,31,33-37,40-48,52-54H,9-11,15-17,20-30,32,67,69H2,1-8H3,(H2,68,84)(H,70,72)(H,71,89)(H,73,90)(H,74,93)(H,75,98)(H,76,97)(H,77,94)(H,78,96)(H,79,95)(H,80,99)(H,82,91)(H,83,92)(H,85,86)(H,87,88)/t35?,36?,37?,40-,41+,42+,43-,44+,45-,46-,47+,48?,52?,53-,54-/m0/s1 checkY
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Bacitracin[1] 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 10716) in 1945.[2] These peptides disrupt Gram-positive bacteria by interfering with cell wall and peptidoglycan synthesis.

Bacitracin is primarily used as a topical preparation, as it can cause kidney damage when used internally.[3] It is generally safe when used topically, but in rare cases may cause hypersensitivity, allergic or anaphylactic reactions, especially in people allergic to neomycin.[4][5]

In 2022, it was the 323rd most commonly prescribed medication in the United States, with more than 100,000 prescriptions.[6]

Medical uses

[edit]
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.[7]

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 infections. A non-ointment form of ophthalmic solution is also available for eye infections.[8]

3D Chemical Structure of Bacitracin

Spectrum of activity and susceptibility data

[edit]

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.[9]

Mechanism of action

[edit]
Main article: Bactoprenol phosphate

Bacitracin interferes with the dephosphorylation of 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.[10]

History

[edit]

Bacitracin was isolated by Balbina Johnson, a bacteriologist at the Columbia University College of Physicians and Surgeons.[11] Its name derives from the fact that a compound produced by a microbe in young Margaret Tracy's (1936–1994)[12] leg injury showed antibacterial activity.[13]

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.[11]

Bacitracin was approved by the US FDA in 1948.[14]

Synthesis

[edit]

Bacitracin is synthesised via nonribosomal peptide synthetases (NRPSs), which means that ribosomes are not directly involved in its synthesis. The three-enzyme operon is called BacABC, not to be confused with BacABCDE of bacilycin synthesis.[15]

Composition

[edit]

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.[16] 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.[17]

Society and culture

[edit]

Controversies

[edit]

Claims that bacitracin is a protein disulfide isomerase inhibitor are disputed by in vitro studies.[18][19]

References

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  1. ^ Elks J, Ganellin CR (1990). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 119–. ISBN 978-1-4757-2085-3.
  2. ^ Originally grouped under B. subtilis, but nomenclature has since changed. See Podstawka A. "Bacillus licheniformis Tracy I | DSM 603, ATCC 10716, CCM 2181, IFO 12199, NBRC 12199, NCIB 8874, FDA BT1 | BacDiveID:686". bacdive.dsmz.de. Archived from the original on 7 February 2022. Retrieved 7 February 2022.
  3. ^ Zintel HA, Ma RA (October 1949). "The absorption, distribution, excretion and toxicity of bacitracin in man". The American Journal of the Medical Sciences. 218 (4): 439–445. doi:10.1097/00000441-194910000-00012. PMID 18140540. S2CID 2371497.
  4. ^ Spann CT, Taylor SC, Weinberg JM (July 2004). "Topical antimicrobial agents in dermatology". Disease-a-Month. 50 (7): 407–421. doi:10.1016/j.disamonth.2004.05.011. PMID 15280871.
  5. ^ Trookman NS, Rizer RL, Weber T (March 2011). "Treatment of minor wounds from dermatologic procedures: a comparison of three topical wound care ointments using a laser wound model". Journal of the American Academy of Dermatology. 64 (3 Suppl): S8-15. doi:10.1016/j.jaad.2010.11.011. PMID 21247665.
  6. ^ "Bacitracin Drug Usage Statistics, United States, 2013 - 2022". ClinCalc. Retrieved 30 August 2024.
  7. ^ Pearl MC (12 September 2007). "Antibiotic use on the farm hurts people—and doesn't help the bottom line". Discover Magazine. Archived from the original on 25 September 2007.
  8. ^ "Healthgrades > Find a Doctor > Doctor Reviews > Hospital Ratings". Archived from the original on 23 May 2011.
  9. ^ "Bacitracin Susceptibility and Minimum Inhibitory Concentration (MIC) Data" (PDF). TOKU-E. Archived (PDF) from the original on 22 December 2018. Retrieved 12 August 2013.
  10. ^ Stone KJ, Strominger JL (December 1971). "Mechanism of action of bacitracin: complexation with metal ion and C 55 -isoprenyl pyrophosphate". Proceedings of the National Academy of Sciences of the United States of America. 68 (12): 3223–7. Bibcode:1971PNAS...68.3223S. doi:10.1073/pnas.68.12.3223. PMC 389626. PMID 4332017.
  11. ^ a b Johnson BA, Anker H, Meleney FL (October 1945). "Bacitracin: a new antibiotic produced by a member of the B. subtilis group". Science. 102 (2650): 376–7. Bibcode:1945Sci...102..376J. doi:10.1126/science.102.2650.376. PMID 17770204. S2CID 51066.
  12. ^ "Margaret Tracy & Balbina Johnson: The Women Behind Bacitracin". Archived from the original on 28 April 2014. Retrieved 30 September 2014.
  13. ^ "NewYork-Presbyterian | the Discovery of Bacitracin". 7 February 2017. Archived from the original on 27 February 2021. Retrieved 9 April 2020.
  14. ^ "Drugs@FDA: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Archived from the original on 27 July 2021. Retrieved 17 September 2021.
  15. ^ Konz D, Klens A, Schörgendorfer K, Marahiel MA (December 1997). "The bacitracin biosynthesis operon of Bacillus licheniformis ATCC 10716: molecular characterization of three multi-modular peptide synthetases". Chemistry & Biology. 4 (12): 927–937. doi:10.1016/s1074-5521(97)90301-x. PMID 9427658.
  16. ^ "Committee for Veterinary Medicinal Products Bacitracin." Ema.europa.eu. The European Agency for the Evaluation of Medicinal Products, June 1998. Web. 18 January 2013
  17. ^ Bell RG (January 1992). "Preparative high-performance liquid chromatographic separation and isolation of bacitracin components and their relationship to microbiological activity". Journal of Chromatography. 590 (1): 163–8. doi:10.1016/0021-9673(92)87018-4. PMID 1601975.
  18. ^ Karala AR, Ruddock LW (June 2010). "Bacitracin is not a specific inhibitor of protein disulfide isomerase". The FEBS Journal. 277 (11): 2454–62. doi:10.1111/j.1742-4658.2010.07660.x. PMID 20477872. S2CID 37519169.
  19. ^ Weston BS, Wahab NA, Roberts T, Mason RM (November 2001). "Bacitracin inhibits fibronectin matrix assembly by mesangial cells in high glucose". Kidney International. 60 (5): 1756–64. doi:10.1046/j.1523-1755.2001.00991.x. PMID 11703593.
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