Bacitracin
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| 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 | OTC/℞-only |
| Routes | Topical, intramuscular |
| Identifiers | |
| CAS number | 1405-87-4  |
| ATC code | D06AX05 J01XX10 R02AB04 QA07AA93 |
| PubChem | CID 439542 |
| DrugBank | DB00626 |
| ChemSpider | 10481985 |
| UNII | 58H6RWO52I |
| KEGG | D00128  |
| ChEMBL | CHEMBL1200558 |
| Chemical data | |
| Formula | C66H103N17O16S |
| Mol. mass | 1422.69 g/mol |
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Bacitracin is a mixture of related cyclic polypeptides produced by organisms of the licheniformis group of Bacillus subtilis var Tracy, isolation of which was first reported 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). Despite frequent topical use, there is little evidence that bacitracin is more effective than simple petroleum jelly for minor wounds.[1] Moreover, bacitracin frequently causes contact dermatitis and was even named the 2003 Allergen of the Year due to this common side-effect.[citation needed]
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]
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History [edit]
The drug's unique name derives from the fact that it was isolated by John T. Goorley from a girl named 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."[6]
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.[7]
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.
Mechanism of action [edit]
Bacitracin interferes with the dephosphorylation of the C55-isoprenyl pyrophosphate, a molecule that carries the building-blocks of the peptidoglycan bacterial cell wall outside of the inner membrane.[8]
Bacitracin has been claimed to be a protein disulfide isomerase inhibitor in cells,[9] but this is disputed by in vitro studies.[10]
Clinical use [edit]
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.[11]
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.[12] 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.
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.[13]
In infants, bacitracin is rarely administered intramuscularly for the treatment of staphylococcal pneumonia and empyema when due to organisms shown to be susceptible to bacitracin. This use is extremely limited, since bacitracin is nephrotoxic and the concentration of bacitracin in the blood must be followed closely.[14]
Bacitracin can be used to distinguish Streptococcus pyogenes from other bacteria,[15] 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 was voted Allergen of the Year in 2003 by the American Contact Dermatitis Society.[citation needed]
References [edit]
- ^ 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. PMID 8805732.
- ^ 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.
- ^ 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.
- ^ Martin, David (14 September 2011). "MRSA in U.S. becoming resistant to over the counter ointment". CNN. Retrieved 2 June 2012.
- ^ Suzuki, M; Yamada, K; Nagao, M; Aoki, E; Matsumoto, M; Hirayama, T; Yamamoto, H; Hiramatsu, R 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.
- ^ 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.
- ^ 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.
- ^ Mechanism of Action of Bacitracin: Complexation with Metal Ion and C55-Isoprenyl Pyrophosphate K. John Stone and Jack L. Strominger
- ^ 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.
- ^ 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.
- ^ Antibiotic use on the farm hurts people—and doesn’t help the bottom line. Discover Magazine. Accessed on September 16, 2007.
- ^ http://www.healthgrades.com/drug-ratings/drug/information/1246/Triple%20Antibiotic
- ^ Tattoo Aftercare Contradictions
- ^ http://www.sagentpharma.com/Products/Bacitracin/Catalog/Bacitracin_PI.pdf FDA-approved IM injection package insert for bacitracin.
- ^ "Streptococcus Group A Infections: Differential Diagnoses & Workup". Retrieved Sep 23, 2009.
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