Бацитрацин

Описание

Bacitracin 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.

Химические свойства

Bacitracin is a white to light tan powder which is odorless or having a slight odor and very bitter taste.

Использование

Bacitracin 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.

Определение

A complex of cyclic peptide antibiotic of known chemical structure isolated from the Tracy-I strain of Bacillus subtilis.

Показания

This 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.

Опасность

Poison; moderately toxic; mutagen.

Фармацевтические приложения

A 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.

Клиническое использование

Bacitracin 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.

Профиль безопасности

A poison by intraperitoneal and intravenous routes. Moderately toxic by ingestion and subcutaneous routes. Mutation data reported.

Возможный контакт

Bacitracin 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.

Перевозки

UN 3249 Medicine, solid, toxic, n.o.s., Hazard Class: 6.1; Labels: 6.1—Poisonous materials.

Методы очистки

Bacitracin 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.]

Несовместимости

Incompatible 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.

Утилизация отходов

It 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.