Bacitracin
Encyclopedia
Bacitracin is a mixture of related cyclic polypeptide
Peptide
Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...

s produced by organism
Organism
In biology, an organism is any contiguous living system . In at least some form, all organisms are capable of response to stimuli, reproduction, growth and development, and maintenance of homoeostasis as a stable whole.An organism may either be unicellular or, as in the case of humans, comprise...

s of the licheniformis group of Bacillus subtilis
Bacillus subtilis
Bacillus subtilis, known also as the hay bacillus or grass bacillus, is a Gram-positive, catalase-positive bacterium commonly found in soil. A member of the genus Bacillus, B. subtilis is rod-shaped, and has the ability to form a tough, protective endospore, allowing the organism to tolerate...

var Tracy, isolation of which was first reported in 1945.

As a toxic and difficult-to-use antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...

, bacitracin does not work well orally. However, it is very effective topically, and is a common ingredient of eye and skin antibiotic preparations. Its action is on Gram-positive
Gram-positive
Gram-positive bacteria are those that are stained dark blue or violet by Gram staining. This is in contrast to Gram-negative bacteria, which cannot retain the crystal violet stain, instead taking up the counterstain and appearing red or pink...

 cell walls. It can cause contact dermatitis and cross-reacts with allergic sensitivity to sulfa-drugs.

When given intramuscularly, bacitracin's absorption is rapid and complete, but its nephrotoxicity (kidney damage potential) has limited its use to infants only, and then in very specific circumstances. In 2010 it was approved by the US FDA by this route for the very narrow indication of treatmnent of infants with staphylococcal pneumonia
Pneumonia
Pneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...

 and empyema
Empyema
Pleural empyema is an accumulation of pus in the pleural cavity. Most pleural empyemas arise from an infection within the lung , often associated with parapneumonic effusions. There are three stages: exudative, fibrinopurulent and organizing. In the exudative stage, the pus accumulates...

 when due to organisms shown to be susceptible to bacitracin. It can only be used where adequate laboratory facilities are available for checking the drug's concentration in blood.

History

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."

It was approved by FDA in 1948.

Synthesis

Bacitracin is synthesised via what is called nonribosomal peptide synthetases (NRPSs), which means that ribosome
Ribosome
A ribosome is a component of cells that assembles the twenty specific amino acid molecules to form the particular protein molecule determined by the nucleotide sequence of an RNA molecule....

s are not involved in its synthesis
Nonribosomal peptide
Nonribosomal peptides are a class of peptide secondary metabolites, usually produced by microorganisms like bacteria and fungi. Nonribosomal peptides are also found in higher organisms, such as nudibranchs, but are thought to be made by bacteria inside these organisms...

.

bacABC is involved in synthesis.

Mechanism of action

Bacitracin interferes with the dephosphorylation of the C
Carbon
Carbon is the chemical element with symbol C and atomic number 6. As a member of group 14 on the periodic table, it is nonmetallic and tetravalent—making four electrons available to form covalent chemical bonds...

55-isoprenyl pyrophosphate, a molecule that carries the building-blocks of the peptidoglycan
Peptidoglycan
Peptidoglycan, also known as murein, is a polymer consisting of sugars and amino acids that forms a mesh-like layer outside the plasma membrane of bacteria , forming the cell wall. The sugar component consists of alternating residues of β- linked N-acetylglucosamine and N-acetylmuramic acid...

 bacterial cell wall
Cell wall
The cell wall is the tough, usually flexible but sometimes fairly rigid layer that surrounds some types of cells. It is located outside the cell membrane and provides these cells with structural support and protection, and also acts as a filtering mechanism. A major function of the cell wall is to...

 outside of the inner membrane.

Bacitracin has been claimed to be a protein disulfide isomerase
Protein disulfide isomerase
Protein disulfide isomerase or PDI is an enzyme in the endoplasmic reticulum in eukaryotes that catalyzes the formation and breakage of disulfide bonds between cysteine residues within proteins as they fold...

 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."

As bacitracin zinc salt, in combination with other topical antibiotics (usually polymyxin B
Polymyxin B
Polymyxin B is an antibiotic primarily used for resistant gram-negative infections. It is derived from the bacterium Bacillus polymyxa. Polymyxin B is a mixture of two closely related compounds, polymyxin B1 and polymyxin B2. It has a bactericidal action against almost all gram-negative bacilli...

 and neomycin
Neomycin
Neomycin is an aminoglycoside antibiotic that is found in many topical medications such as creams, ointments, and eyedrops. The discovery of Neomycin dates back to 1949. It was discovered in the lab of Selman Waksman, who was later awarded the Nobel Prize in Physiology and medicine in 1951...

) as an ointment ("triple antibiotic ointment," with a common brand name Neosporin
Neosporin
Neosporin is the product branding & formulas now owned by Johnson & Johnson of an antibiotic over-the-counter topical created under Warner-Lambert Consumer Healthcare, now a part of Pfizer...

), it is used for topical treatment of a variety of localized skin and eye infections, as well as for the prevention of wound infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...

s. A non-ointment form of opthalmic 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. It is preferred over combination products such as Neosporin because of its fewer ingredients, which lowers chances of an allergic reaction.

In infants, bacitracin is sometimes administered intramuscularly for the treatment of pneumonia
Pneumonia
Pneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...

 due to Staphylococci, but in most cases other antibiotics are used, and bacitracin is reserved only for MRSA and other strains resistant to multiple other safer antibiotics. This formulation is sold under the brand name Baci-IM.

Bacitracin can be used to distinguish Streptococcus pyogenes
Streptococcus pyogenes
Streptococcus pyogenes is a spherical, Gram-positive bacterium that is the cause of group A streptococcal infections. S. pyogenes displays streptococcal group A antigen on its cell wall. S...

from other bacteria, with S. pyogenes being sensitive to bacitracin and others resistant.

Note: Bacitracin is in this case used to distinguish S. pyogenes from other β-hemolytic streptococcus
Streptococcus
Streptococcus is a genus of spherical Gram-positive bacteria belonging to the phylum Firmicutes and the lactic acid bacteria group. Cellular division occurs along a single axis in these bacteria, and thus they grow in chains or pairs, hence the name — from Greek στρεπτος streptos, meaning...

.

It was voted Allergen of the Year
Allergen of the Year
Allergen of the Year is an annual 'award' of dubious distinction voted upon by the American Contact Dermatitis Society. It is "designed to draw attention to allergens that are very common and/or under-recognized and merit more attention because they are causing significant allergic contact...

in 2003 by the American Contact Dermatitis Society.
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