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.
The widespread use of bacitracin, even for minor wounds where it is not useful, contributes to antibiotic resistance. This widespread use has contributed to the emergence of MRSA bacteria, specifically the highly lethal ST8:USA300 strain.
History
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): 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."
It was approved by FDA in 1948.
Synthesis
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.
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
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. Other bacitracin components including F and X do not appear to be extensively studied.
Spectrum of activity and susceptibility data
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 â€" ≤0.03 μg/mL â€" 700 μg/mL
- Staphylococcus epidermidis â€" 0.25 μg/mL â€" >16 μg/mL
- Streptococcus pyogenes â€" 0.5 μg/mL â€" >16 μg/mL
Mechanism of action
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.
Some have claimed that bacitracin is a protein disulfide isomerase inhibitor in cells, but this is disputed by in vitro studies.
Clinical use
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.
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.
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.
In 2005â€"06, it was the sixth-most-prevalent allergen in patch tests (9.2%).
It was voted Allergen of the Year in 2003 by the American Contact Dermatitis Society.
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.
Bacitracin can be used to distinguish Streptococcus pyogenes from other "strep" bacteria, 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.
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