Bacitracin

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 Y
ATC code	D06AX05 J01XX10 R02AB04 QA07AA93
PubChem	CID 439542
DrugBank	DB00626
ChemSpider	10481985 Y
UNII	58H6RWO52I Y
KEGG	D00128 N
ChEMBL	CHEMBL1200558 N
Chemical data
Formula	C66H103N17O16S
Mol. mass	1422.69 g/mol
SMILES O=C(O)C[C@H]3NC(=O)[C@H](Cc1cncn1)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@@H](NC(=O)[C@@H](CCCN)NC(=O)[C@H](CCCCNC(=O)[C@H](CC(N)=O)NC3=O)NC(=O)[C@@H](NC(=O)[C@@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)C4N=C(SC4)\nC(N)C(C)CC)C(C)CC)C(C)CC
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 Y Key:CLKOFPXJLQSYAH-NVOBBBONSA-N Y
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, isolation of which was first reported in 1945.

As a toxic and difficult-to-use antibiotic, 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 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 treatment of infants with staphylococcal pneumonia and empyema 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.^[1]

  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."^[2]

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.^[3]

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

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.^[4]

Bacitracin has been claimed to be a protein disulfide isomerase inhibitor in cells,^[5] but this is disputed by in vitro studies.^[6]

  Clinical use

  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."^[7]

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.^[8] 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. It is preferred over combination products such as Neosporin because of its fewer ingredients, which lowers chances of an allergic reaction.^[9]

In infants, bacitracin is sometimes administered intramuscularly for the treatment of pneumonia 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.^[1]

Bacitracin can be used to distinguish Streptococcus pyogenes from other bacteria,^[10] 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.

  References