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Bacitracin

Clinical data
Trade names	Baciguent, Baciim, others
AHFS/Drugs.com	Monograph
Pregnancy category	AU: D
Routes of administration	Topical, intramuscular, Ophthalmic drug administration
ATC code	D06AX05 (WHO) J01XX10 (WHO), R02AB04 (WHO), S01AA32 (WHO), QA07AA93 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) US: OTC / Rx-only
Identifiers
IUPAC name (4R)-4-- 4,5-dihydro-1,3-thiazol-5-yl}formamido)-4-methylpentanamido]-4-{carbamoyl}- 2-methylbutyl]carbamoyl}butanoic acid
CAS Number	1405-87-4
PubChem CID	439542
DrugBank	DB00626
ChemSpider	10481985
UNII	58H6RWO52I
KEGG	D00128
ChEBI	CHEBI:28669
ChEMBL	ChEMBL1200558
Chemical and physical data
Formula	C66H103N17O16S
Molar mass	1422.71 g·mol
3D model (JSmol)	Interactive image
SMILES CCC(C)C(N)NC4=NC(C(=O)N(CC(C)C)C(=O)N(CCC(O)=O)C(=O)N(C(C)CC)C(=O)N3CCCCNC(=O)(CC(N)=O)NC(=O)(CC(O)=O)NC(=O)(Cc1cnc1)NC(=O)(Cc2ccccc2)NC(=O)(C(C)CC)NC(=O)(CCCN)NC3=O)CS4
InChI 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 Key:CLKOFPXJLQSYAH-NVOBBBONSA-N
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Bacitracin 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. 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. It is generally safe when used topically, but in rare cases may cause hypersensitivity, allergic or anaphylactic reactions, especially in people allergic to neomycin.

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

Medical uses

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.

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.

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.

• Staphylococcus aureus – ≤0.03 μg/mL – 700 μg/mL
• Staphylococcus epidermidis – 0.25 μg/mL – >16 μg/mL
• Streptococcus pyogenes – 0.5 μg/mL – >16 μg/mL

Mechanism of action

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.

History

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

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.

Bacitracin was approved by the US FDA in 1948.

Synthesis

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.

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. 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.

Society and culture

Controversies

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

References

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. ^ 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.

• Medicine

• Polypeptide antibiotics
• Cyclic peptides