Bacitracin Chemical Properties
- Melting point:221-225°C
- Density 1.0166 (rough estimate)
- refractive index 1.6700 (estimate)
- storage temp. 2-8°C
- solubility H2O: 50 mg/mL, clear to very slightly hazy, deep yellow
- form Powder
- color white to faintly beige
- Odorodorlessor slt odor
- Water Solubility soluble
- Merck 13,936
- EPA Substance Registry SystemBacitracin (1405-87-4)
Bacitracin Usage And Synthesis
- Mode of actionThe lipid carrier involved in transporting the cell wall building block across the membrane is a C55 isoprenyl phosphate. The lipid acquires an additional phosphate group in the transport process and must be dephosphorylated in order to regenerate the native compound for another round of transfer. Bacitracin as cyclic peptide antibiotics binds to the C55 lipid carrier. Bacitracin inhibits its dephosphorylation thus disrupting the lipid carrier cycle.
- DescriptionBacitracin is a mixture of similar peptides produced by fermentation of the bacterium Bacillus subtil is. The A-type component predominates. Its mode of action is to inhibit both peptidoglycan biosynthesis at a late stage (probably at the dephosphorylation of the phospholipid carrier step) and disruptions of plasma membrane function.
- Chemical PropertiesWhite to pale buff powder
- Chemical PropertiesBacitracin is a white to light tan powder which is odorless or having a slight odor and very bitter taste.
- UsesPolypeptide antibacterial.
- UsesBacitracin is a peptide antibiotic effective against gram-postive bacteria. Bacitracin is an inhibitor of peptidoglycan synthesis. Bacitracin disrupts bacterial cell wall synthesis by inhibiting depho sphorylation of lipid pyrophosphate. Bacitracin also strongly inhibits proline endopeptidase from human muscle.
- Usesantibiotic agent effective against gram-positive organisms and spirochetes; in products for topieal treatment, ear medications and ophthalmie drugs
- IndicationsThis polypeptide antibiotic, which is produced from Bacillus subtilis,
interferes with bacterial cell wall growth and is bactericidal against many grampositive
organisms such as streptococci, staphylococci, and pneumococci but is
inactive against most gram-negative organisms. All anaerobic cocci, Neisseria, and
the tetanus and diphtheria bacilli are also sensitive to bacitracin.
Resistance is rare, but some staphylococcal strains are inherently resistant. Hypersensitivity reactions are uncommon. Bacitracin is stable in petrolatum (but not water-miscible preparations) and is available as an ointment or as a component of antibiotic mixtures. Sensitization to bacitracin has been reported more recently, particularly in patients with leg ulcers.
- DefinitionA complex of cyclic peptide antibiotic of known chemical structure isolated from the Tracy-I strain of Bacillus subtilis.
- Manufacturing ProcessThe early patent, US Patent 2,498,165 first disclosed bacitracin and described
a process for preparing bacitracin, comprising cultivating Bacillus subtilis Tracy
I in a nutritive medium, at substantially pH 7 and 37°C, for more than three
days, extracting the antibiotic from the resulting medium with a low molecular
weight alcohol, concentrating the resulting alcoholic solution in vacuo,
acidifying the resulting concentrate, extracting the antibiotic from the resulting
solution, and precipitating the antibiotic from the resulting solution, with a
precipitating agent for the antibiotic, selected from the group consisting of
Reinecke's salt, phosphotungstic acid, phosphomolybdic acid, molybdic acid,
picric acid, ammonium rhodanilate, and azobenzene-p-sulfonicacid.
A subsequent patent, US Patent 2,828,246 described a commercial process for bacitracin production. A 1,230 gallon portion of a medium containing 10% soybean oil meal, 2.50% starch and 0.50% calcium carbonate having a pH of 7.0 was inoculated with a culture of bacitracin-producing bacteria of the Bacillus subtilis group and the inoculated medium incubated for a period of 24 hours with aeration such that the superficial air velocity was 12.1. An assay of the nutrient medium following the fermentation revealed a yield of bacitracin amounting to 323 units/ml. This was more than twice the yields previously obtained.
Then, a patent, US Patent 2,834,711 described the purification of bacitracin. In this process for purifying bacitracin, the steps comprise adding a watersoluble zinc salt to a partially purified aqueous solution of bacitracin, adjusting the pH to from 5 to 9, recovering the precipitate which forms, dissolving the precipitate in water at a pH not substantially in excess of 4, and removing the zinc ion by passing the aqueous solution through a cation exchange resin and drying the resulting solution to obtain dry solid bacitracin.
Another patent, US Patent 2,915,432describes a process of recovering and concentrating bacitracin from aqueous filtered fermentation broth containing on the order of 3% protein-aceous solids which comprises intimately contacting the broth with a synthetic organic cation exchange resin having as its functional groups nuclear sulfonic acids and having a crosslinkage of the order of 1 to 2%, with the resin being in the hydrogen form, and eluting the adsorbed bacitracin from the resin with a weak base.
Bacitracin recovery is described in US Patents 3,795,663 and 4,101,539.
- brand nameZiba (X Gen).
- Therapeutic FunctionAntibacterial
- General DescriptionThe organism from which Johnson et al. produced bacitracinin 1945 is a strain of B. subtilis. The organism hadbeen isolated from debrided tissue from a compound fracturein 7-year-old Margaret Tracy, hence the name “bacitracin.”Bacitracin is now produced from the licheniformisgroup (B. subtilis). Like tyrothricin, the first useful antibioticobtained from bacterial cultures, bacitracin is a complex mixture of polypeptides. So far, at least 10 polypeptideshave been isolated by countercurrent distribution techniques:A, A1, B, C, D, E, F1, F2, F3, and G. The commercialproduct known as bacitracin is a mixture of principallyA, with smaller amounts of B, D, E, and F1–3.The official product is a white to pale buff powder that isodorless or nearly so.
The activity of bacitracin is measured in units per milligram.The potency per milligram is not less than40 units/mg except for material prepared for parenteral use,which has a potency of not less than 50 units/mg. It is a bactericidalantibiotic that is active against a wide variety ofGram-positive organisms, very few Gram-negative organisms,and some others. It is believed to exert its bactericidaleffect through inhibition of mucopeptide cell wall synthesis.Its action is enhanced by zinc. Although bacitracin hasfound its widest use in topical preparations for local infections,it is quite effective in several systemic and local infectionswhen administered parenterally. It is not absorbedfrom the GI tract; accordingly, oral administration is withouteffect, except for the treatment of amebic infectionswithin the alimentary canal.
- Hazard Poison; moderately toxic; mutagen.
- Pharmaceutical ApplicationsA mixture of peptides produced by Bacillus licheniformis.
Bacitracin A is the major constituent of commercial preparations.
The more stable zinc salt is used in topical formulations.
It has been widely used as a growth promoter in animals, but
has been banned for that purpose in the European Union.
It is highly active against many Gram-positive bacteria and is mainly used as a component of topical preparations. Although strains of Staph. aureus are usually susceptible, they are rather less so than most other Gram-positive bacteria. Streptococcus pyogenes is so much more susceptible than other hemolytic streptococci that bacitracin susceptibility is used as a screening test for identification. Clostridium difficile and Actinomyces spp. are susceptible, but enterobacteria and Pseudomonas spp. are resistant. Entamoeba histolytica is inhibited by 0.6–10 mg/L.
Resistance is uncommon, but has been detected in Staph. aureus following topical treatment.
It is nephrotoxic and unsuitable for parenteral use. Systemic toxicity from application to skin or ulcerated areas is rare, but it may cause allergic reactions and occasional anaphylaxis has been described. It is found in many ointments and ophthalmic preparations, usually together with other components, including polymyxins, neomycin and corticosteroids.
Bacitracin is not absorbed by mouth but oral preparations have been used for suppression of gut flora, including C. difficile.
- Clinical UseBacitracin is predominantly active against Gram-positive microorganisms, and parenteral use is limited to IM injection for infants with pneumonia and empyema caused by staphylococci resistant to other agents. It is rather neuro- and nephrotoxic and, therefore, is used in this manner with caution. Bacitracin also is widely employed topically to prevent infection in minor cuts, scrapes, and burns.
- Safety ProfileA poison by intraperitoneal and intravenous routes. Moderately toxic by ingestion and subcutaneous routes. Mutation data reported.
- Potential ExposureBacitracin is used as an ingredient in antibiotic ointments to treat or prevent topical or eye infections. Commercial Bacitracin is a mixture of at least 9 bacitracins. Also used as a feed and drinking water additive for animals; as a food additive for human consumption.
- ShippingUN 3249 Medicine, solid, toxic, n.o.s., Hazard Class: 6.1; Labels: 6.1—Poisonous materials.
- Purification MethodsBacitracin has been purified by carrier displacement using n-heptanol, n-octanol and n-nonanol as carriers and 50% EtOH in 0.1 N HCl. The pure material gives one spot with RF ~0.5 on paper chromatography using AcOH:n-BuOH:H2O (4:1:5). [Porath Acta Chem Scand 6 1237 1952.] It has also been purified by ion-exchange chromatography. It is a white powder soluble in H2O and EtOH but insoluble in Et2O, CHCl3 and Me2CO. It is stable in acidic solution but unstable in base. It is a strong antibacterial. [Abraham & Bewton Biochem J 47 257 1950, Synthesis: Munekata et al. Bull Chem Soc Jpn 46 3187, 3835 1973, Beilstein 27 III/IV 5746.]
- IncompatibilitiesIncompatible with oxidizers (chlorates, nitrates, peroxides, permanganates, perchlorates, chlorine, bromine, fluorine, etc.); contact may cause fires or explosions. Keep away from alkaline materials, strong bases, strong acids, oxoacids, epoxides.
- Waste DisposalIt is inappropriate and possibly dangerous to the environment to dispose of expired or waste pharmaceuticals by flushing them down the toilet or discarding them to the trash. Household quantities of expired or waste pharmaceuticals may be mixed with wet cat litter or coffee grounds, double-bagged in plastic, discard in trash. Larger quantities shall carefully take into consideration applicable DEA, EPA, and FDA regulations. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.
Bacitracin Preparation Products And Raw materials
- bacitracin F,Bacitracin H3,bacitracin F,Bacitracin H3 1-[N-[[2-(1-Amino-2-methylbuyl)-4,5-dihydro-4-thiazolyl]carbonyl]-L-leucine]bacitracin F,Bacitracin F, 1-[N-[[2-(1-amino-2-methylbutyl)-4,5-dihydro-4-thiazolyl]carbonyl]-l-leucine]- ,1-[N-[[2-(1-Amino-2-methylbuyl)-4,5-dihydro-4-thiazolyl]carbonyl]-L-leucine]bacitracin F,Bacitracin F, 1-[N-[[2-(1-amino-2-methylbutyl)-4,5-dihydro-4-thiazolyl]carbonyl]-l-leucine]- Bacitracin EP Impurity L Bacitracin Related Compound 1 Bacitracin EP Impurity M Bacitracin Related Compound 2 TRIS(2,2,6,6-TETRAMETHYL-3,5-HEPTANEDIONATO)DYSPROSIUM(III) Tris(2,4-pentanedionato)chroMiuM(III) METHYL ISOCYANOACETATE DICHLORO(ETHYLENEDIAMINE)PLATINUM(II) Tosylmethyl isocyanide BENZYL ISOCYANIDE TRIS(2,2,6,6-TETRAMETHYL-3,5-HEPTANEDIONATO)EUROPIUM(III) N-BUTYLISOCYANIDE Bacitracin CARBONYL SULFIDE BACITRACIN U.S.P. ACTIVITY: 60 UNITS/MG MINIMUM ZINC SALT,Bacitracin Zinc USP,Bacitracin, zinc salt, potency min. 60 Units/mg,bacitracin zinc salt from bacillus licheniformis,Polymyxin B Sulfate bacitracin zinc,ZINC BACITRACIN USP,BACITRACIN ZINC,BACITRACIN ZINC SALT,ZINC BACITRACIN,BACITRACIN ZINC SALT USP,Bacitracin Zinc salt from Bacillus sp.,BACITRACIN ZINC SALT USP,Bacitracin Zinc salt from Bacillus sp.,Bacitracin Zinc USP,Bacitracin, zinc salt, potency min. 60 Units/mg,BACITRACIN U. Glycine
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