Bacitracin

Bacitracin
Names
Trade namesBaciim
IUPAC name
  • (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
Clinical data
Drug classAntibiotic
Main usesSuperficial bacterial skin infections, bacterial conjunctivitis[1][2]
Side effectsTopical: Irritation, rash., allergic reactions[2]
Injection: Kidney problems[3]
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
  • AU: D
  • US: C (Risk not ruled out)
    Routes of
    use    		Topical, intramuscular
    External links
    AHFS/Drugs.comSystemic: Monograph
    Topical: Monograph
    Eye: Monograph
    Legal
    Legal status
    • AU: S4 (Prescription only)
    • US: OTC for topical administration; Rx-only for injection
    Chemical and physical data
    FormulaC66H103N17O16S
    Molar mass1422.71 g·mol−1
    3D model (JSmol)
    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
    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 checkY
    • Key:CLKOFPXJLQSYAH-NVOBBBONSA-N checkY

    Bacitracin is an antibiotic.[3] When applied to the skin, it is used to treat superficial bacterial skin infections.[2] When applied to the eyes, it is used to treat bacterial conjunctivitis.[1] It has also been used by mouth to treat Clostridioides difficile diarrhea, but is not a preferred treatment.[3]

    Common side effects when applied to the skin or eyes include irritation and rash.[2] Other side effects may include allergic reactions.[2] When given by injected kidney problems may occur.[3] Safety in pregnancy is unclear.[2] It works by interfering with the building of a cell wall.[1]

    Bacitracin was first isolated in 1945 and approved for medical use in the United States in 1948.[4][3] It is available as a generic medication.[5] In the United States a 3.5 gram tube for use in the eyes costs about 31 USD as of 2022.[5] It was isolated form Bacillus licheniformis.[4] It is also available in combination with other medications.[2]

    Medical uses

    A tube of bacitracin ointment for eyes

    Bacitracin is often combined with other topical antibiotics (usually polymyxin B and neomycin) as an ointment ("triple antibiotic ointment," sold under the brand name Neosporin among others). It is used for 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 superficial eye infections.[6]

    Although allergic cross-reaction with sulfa drugs has been reported, bacitracin-containing topical preparations remain a possible alternative to silver sulfadiazine for people with burns and a sulfa allergy.

    Bacitracin can also be bought in pure form for those with allergies to the usual polymyxin B and neomycin components of the combination product.

    Bacitracin is also commonly used as an aftercare antibiotic on tattoos and circumcision. It is preferred over combination products such as Neosporin because of its fewer ingredients, which lowers chances of an allergic reaction.[7]

    In 2005–06, it was the sixth-most-prevalent allergen in patch tests (9.2%).[8]

    It was voted Allergen of the Year in 2003 by the American Contact Dermatitis Society.[9]

    In infants, bacitracin is rarely administered intramuscularly for the treatment of staphylococcal pneumonia and empyema when due to organisms shown susceptible to bacitracin. This use is extremely limited, since bacitracin is nephrotoxic and its concentration in the blood must be followed closely.[10]

    Bacitracin can be used to distinguish Streptococcus pyogenes from other streptococci,[11] with S. pyogenes being sensitive to bacitracin and others resistant. In this case bacitracin is used to distinguish S. pyogenes from other β-hemolytic streptococci.

    It is also commonly used to distinguish Haemophilus influenzae colonies amongst respiratory flora; since H. influenzae is intrinsically resistant to bacitracin, colonies form within the zone of inhibition.

    Spectrum of activity

    Bacitracin is a narrow-spectrum antibiotic. It targets Gram-positive organisms, especially those that cause skin infections. The following represents susceptibility data for a few medically significant microorganisms.[12]

    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.[13]

    Some have claimed that bacitracin is a protein disulfide isomerase inhibitor, but this is disputed by in vitro studies.[14][15]

    Chemistry

    3D chemical structure of bacitracin

    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.[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] Other bacitracin components including F and X do not appear to be extensively studied.

    Synthesis

    Bacitracin is synthesised via nonribosomal peptide synthetases (NRPSs), which means that ribosomes are not directly involved in its synthesis.

    bacABC is involved in synthesis.[18]

    Bacitracin is commercially manufactured by growing the bacteria Bacillus subtilis var Tracy I in a container of liquid growth medium. Over time, the bacteria synthesizes the antibiotic and secretes the antibiotic into the medium. The antibiotic is then extracted from the medium using chemical processes.

    History

    Bacitracin was isolated by Balbina Johnson, a bacteriologist at the Columbia University College of Physicians and Surgeons.[19] Its name derives from the fact that a compound produced by a microbe in young Margaret Treacy's (1936–1994)[20] leg injury showed antibacterial activity.[21] The surname was misspelled and the name shortened to the more common spelling "Tracy."

    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.[19]

    Bacitracin was approved by FDA in 1948.

    Other animals

    It is also "approved by the U.S. Food and Drug Administration (FDA) for use in chickens and turkeys," though use in animals contributes to antibiotic resistance.[22]

    References

    1. 1 2 3 "Bacitracin (EENT) Monograph for Professionals". Drugs.com. Archived from the original on 16 July 2017. Retrieved 8 January 2022.
    2. 1 2 3 4 5 6 7 "Bacitracin (Topical) Monograph for Professionals". Drugs.com. Archived from the original on 8 December 2021. Retrieved 8 January 2022.
    3. 1 2 3 4 5 "Bacitracin Monograph for Professionals". Drugs.com. Archived from the original on 25 February 2021. Retrieved 7 January 2022.
    4. 1 2 Hahn, Fred E. (6 December 2012). Mechanism of Action of Antibacterial Agents. Springer Science & Business Media. p. 1. ISBN 978-3-642-46403-4. Archived from the original on 11 January 2022. Retrieved 7 January 2022.
    5. 1 2 "Bacitracin Prices, Coupons & Savings Tips - GoodRx". GoodRx. Archived from the original on 12 October 2016. Retrieved 7 January 2022.
    6. ↑ "Healthgrades > Find a Doctor > Doctor Reviews > Hospital Ratings". Archived from the original on 2011-05-23.
    7. ↑ "The Right Way to Take Care of a New Tattoo". Archived from the original on 2007-08-13.
    8. ↑ Zug KA, Warshaw EM, Fowler JF Jr, Maibach HI, Belsito DL, Pratt MD, Sasseville D, Storrs FJ, Taylor JS, Mathias CG, Deleo VA, Rietschel RL, Marks J. Patch-test results of the North American Contact Dermatitis Group 2005–2006. Dermatitis. 2009 May–Jun;20(3):149-60.
    9. ↑ "History of Allergen of the Year". American Contact Dermatitis Society. Archived from the original on 2014-04-25.
    10. ↑ "FDA-approved IM injection package insert for bacitracin" (PDF). sagentpharma.com. Archived from the original (PDF) on 2011-05-16.
    11. ↑ "Streptococcus Group A Infections: Differential Diagnoses & Workup". Archived from the original on 2009-08-28. Retrieved Sep 23, 2009.
    12. ↑ "Bacitracin Susceptibility and Minimum Inhibitory Concentration (MIC) Data" (PDF). TOKU-E. Archived (PDF) from the original on 2018-12-22. Retrieved 2021-07-05.
    13. ↑ 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.
    14. ↑ 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.
    15. ↑ 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.
    16. ↑ "Committee for Veterinary Medicinal Products Bacitracin." Ema.europa.eu. The European Agency for the Evaluation of Medicinal Products, June 1998. Web. 18 Jan. 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. ↑ Murphy T, Roy I, Harrop A, Dixon K, Keshavarz T (September 2007). "Effect of oligosaccharide elicitors on bacitracin A production and evidence of transcriptional level control". Journal of Biotechnology. 131 (4): 397–403. doi:10.1016/j.jbiotec.2007.07.943. PMID 17825450.
    19. 1 2 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.
    20. ↑ "Archived copy". Archived from the original on 2014-04-28. Retrieved 2014-09-30.{{cite web}}: CS1 maint: archived copy as title (link)
    21. ↑ "Archive copy". Archived from the original on 2021-02-27. Retrieved 2021-07-05.{{cite web}}: CS1 maint: archived copy as title (link)
    22. ↑ 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 2007-09-25.
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