Bacitracin

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Bacitracin
Bacitracin A.svg
Bacitracin ball-and-stick.png
Systematic (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
Trade names Baciim
AHFS/Drugs.com monograph
Pregnancy cat.
Legal status
Routes Topical, intramuscular
Identifiers
CAS number 1405-87-4 YesY
ATC code D06AX05 J01XX10 R02AB04 QA07AA93
PubChem CID 439542
DrugBank DB00626
ChemSpider 10481985 YesY
UNII 58H6RWO52I YesY
KEGG D00128 N
ChEMBL CHEMBL1200558 N
Chemical data
Formula C66H103N17O16S 
Mol. mass 1422.69 g/mol
 N (what is this?)  (verify)

Bacitracin is a mixture of related cyclic polypeptides produced by organisms of the licheniformis group of Bacillus subtilis var Tracy, first isolated in 1945. These peptides disrupt both gram positive and gram negative bacteria by interfering with cell wall and peptidoglycan synthesis.

Bacitracin is used as a topical preparation (since it is toxic and has poor oral bioavailability). In terms of adverse reactions only, in comparison with bacitracin, white petrolatum possesses an equally low infection rate and minimal risk for induction of allergy.[1]

The widespread use of bacitracin, even for minor wounds where it is not useful, contributes to antibiotic resistance.[2][3] This widespread use has contributed to the emergence of MRSA bacteria,[4] specifically the highly lethal ST8:USA300 strain.[5]

History[edit]

The drug's unique name derives from the fact that it was isolated by John T. Goorley from a girl named Margaret Treacy (1936-1994):[6] The surname was misspelled and the name was 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."[7]

It was approved by FDA in 1948.

Synthesis[edit]

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

bacABC is involved in synthesis.[8]

Bacitracin is commercially manufactured by growing the bacteria Bacillus subtilis 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.

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.[9] 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.[10] Other bacitracin components including F and X do not appear to be extensively studied.

Spectrum of activity and susceptibility data[edit]

Bacitracin is a broad spectrum antibiotic. It targets both Gram-positive and Gram-negative 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

[11]

Mechanism of action[edit]

Main article: Bactoprenol phosphate

Bacitracin interferes with the dephosphorylation of C55-isoprenyl pyrophosphate, a molecule that carries the building-blocks of the peptidoglycan bacterial cell wall outside of the inner membrane.[12]

Some have claimed that bacitracin is a protein disulfide isomerase inhibitor in cells,[13] but this is disputed by in vitro studies.[14]

Clinical use[edit]

A tube of bacitracin ointment for eyes

Bacitracin is used in human medicine as a polypeptide antibiotic and is "approved by the U.S. Food and Drug Administration (FDA) for use in chickens and turkeys," though use in animals contributes to antibiotic resistance.[15]

As bacitracin zinc salt, in combination with other topical antibiotics (usually polymyxin B and neomycin) as an ointment ("triple antibiotic ointment," with a common 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.[16]

Although allergic cross reaction with sulfa drugs has been occasionally reported, bacitracin-containing topical preparations remain a possible alternative to silver sulfadiazine (Silvadene) for burn patients with a sulfa allergy.

3D Chemical Structure of Bacitracin


Bacitracin can also be bought in pure form for those with allergies to the 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.[17]

In 2005–06, it was the sixth-most-prevalent allergen in patch tests (9.2%).[18]

It was voted Allergen of the Year in 2003 by the American Contact Dermatitis Society.[19]

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 the concentration of bacitracin in the blood must be followed closely.[20]

Bacitracin can be used to distinguish Streptococcus pyogenes from other "strep" bacteria,[21] 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.

References[edit]

  1. ^ Smack, DP; Harrington, AC; Dunn, C; Howard, RS; Szkutnik, AJ; Krivda, SJ; Caldwell, JB; James, WD (1996). "Infection and allergy incidence in ambulatory surgery patients using white petrolatum vs bacitracin ointment. A randomized controlled trial". JAMA: the Journal of the American Medical Association 276 (12): 972–7. doi:10.1001/jama.1996.03540120050033. PMID 8805732. 
  2. ^ Spann, CT; Taylor, SC; Weinberg, JM (2004). "Topical antimicrobial agents in dermatology". Disease-a-month : DM 50 (7): 407–21. doi:10.1016/j.disamonth.2004.05.011. PMID 15280871. 
  3. ^ Trookman, NS; Rizer, RL; Weber, T (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. 
  4. ^ Martin, David (14 September 2011). "MRSA in U.S. becoming resistant to over the counter ointment". CNN. Retrieved 2 June 2012. 
  5. ^ Suzuki, M; Yamada, K; Nagao, M; Aoki, E; Matsumoto, M; Hirayama, T; Yamamoto, H; Hiramatsu, R; Ichiyama, S et al. (2011). "Antimicrobial ointments and methicillin-resistant Staphylococcus aureus USA300". Emerging Infectious Diseases 17 (10): 1917–20. doi:10.3201/eid1710.101365. PMC 3310646. PMID 22000371. 
  6. ^ https://files.nyu.edu/jmm257/public/other/bacitracin.html
  7. ^ Johnson B, Anker H, Meleney F (1945). "Bacitracin: a new antibiotic produced by a member of the B. subtilis group".Science 102 (2650): 376–377.
  8. ^ Murphy, T.; Roy, I.; Harrop, A.; Dixon, K.; Keshavarz, T. (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.  edit
  9. ^ "Committee for Veterinary Medicinal Products Bacitracin." Ema.europa.eu. The European Agency for the Evaluation of Medicinal Products, June 1998. Web. 18 Jan. 2013
  10. ^ Bell, Robert G. "Preparative High-Performance Liquid Chromatographic Separation and Isolation of Bacitracin Components and Their Relationship to Microbiological Activity." Journal of Chromatography 590 (1992): 163–68. Web. 21 Aug. 2012.
  11. ^ http://www.toku-e.com/Assets/MIC/Bacitracin.pdf
  12. ^ Mechanism of Action of Bacitracin: Complexation with Metal Ion and C55-Isoprenyl Pyrophosphate K. John Stone and Jack L. Strominger
  13. ^ Weston, B.; Wahab, N.; Roberts, T.; Mason, R. (2001). "Bacitracin inhibits fibronectin matrix assembly by mesangial cells in high glucose". Kidney international 60 (5): 1756–1764. doi:10.1046/j.1523-1755.2001.00991.x. PMID 11703593.  edit
  14. ^ Karala, A. R.; Ruddock, L. W. (2010). "Bacitracin is not a specific inhibitor of protein disulfide isomerase". FEBS Journal 277 (11): 2454–2462. doi:10.1111/j.1742-4658.2010.07660.x. PMID 20477872.  edit
  15. ^ Antibiotic use on the farm hurts people—and doesn’t help the bottom line. Discover Magazine. Accessed on September 16, 2007.
  16. ^ http://www.healthgrades.com/drug-ratings/drug/information/1246/Triple%20Antibiotic
  17. ^ Tattoo Aftercare Contradictions
  18. ^ 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.
  19. ^ History of Allergen of the Year. American Contact Dermatitis Society. Accessed on April 24, 2014.
  20. ^ FDA-approved IM injection package insert for bacitracin.
  21. ^ "Streptococcus Group A Infections: Differential Diagnoses & Workup". Retrieved Sep 23, 2009.