Colistin sulfate

그림문자(GHS)

• 그림문자(GHS)

  

• 신호 어

  Danger

• 유해·위험 문구

  H301：삼키면 유독함

Colistin sulfate 화학적 특성, 용도, 생산

• 화학적 성질

  White or almost white, hygroscopic powder.

• 용도

  Colistin sulfate A Polymyxin potent antibiotic and apoptosis inducer. This compound induces apoptosis through interaction with the cytoplasmic membrane. Colistin is a key microbiological component in Colistin Oxolinic Acid Blood Agar utilized in the cultivation of Aminobacter aminovorans, Bacillus species, Hyphomicrobium species and Methylobacterium species. It is also a critical component is VCN Inhibitor & VCNT Inhibitor growth media used in the isolation of Neisseria species.

• Antimicrobial activity

  All the polymyxins have a similar antibacterial spectrum, although there are slight quantitative differences in their activity in vitro. They are inactive against Gram-positive organisms, but nearly all enterobacteria, except Proteus spp., Burkholderia cepacia and Ser. marcescens, are highly susceptible. The MIC of polymyxin B or colistin sulfate for Esch. coli and Klebsiella spp. is 0.01–1 mg/L; the corresponding concentration for Ps. aeruginosa is 0.03–4 mg/L. Bacteroides fragilis is resistant, but other Bacteroides spp. and fusobacteria are susceptible. Resistance of V. cholerae eltor to polymyxin B distinguishes it from the classic vibrio.
  The sulfomethyl derivatives are generally 4–8 times less active than the sulfates, but their activity is difficult to measure precisely since on incubation they spontaneously decay to the parent compound, with a corresponding progressive increase in antibacterial activity.
  Binding of polymyxins to the bacterial cell membrane can increase permeability to hydrophilic compounds, including sulfonamides and trimethoprim, producing significant synergy. Synergy with ciprofloxacin is also described. Calcium ions exert a strong pH-dependent competition for membrane binding sites, and the presence of calcium and magnesium ions in certain culture media adversely affects the bactericidal activity, notably against Ps. aeruginosa.

• 원료

  There is complete cross-resistance between the polymyxins, but stable acquired resistance in normally susceptible species is very rare. Adaptive resistance, probably due to changes in cell-wall permeability, is readily achieved by passage of a variety of enterobacteria in the presence of the agents in vitro.

• 일반 설명

  In 1950, Koyama et al. isolated an antibiotic fromAerobacillus colistinus (B. polymyxa var. colistinus) thatwas given the name colistin (Coly-Mycin S). It was used inJapan and in some European countries for several years beforeit was made available for medicinal use in the UnitedStates. It is recommended especially for the treatment of refractory urinary tract infections caused by Gram-negativeorganisms such as Aerobacter, Bordetella, Escherichia,Klebsiella, Pseudomonas, Salmonella, and Shigella spp.
  Chemically, colistin is a polypeptide, reported by Suzukiet al. whose major component is colistin A. They proposedthe structure for colistin A differs from polymyxin B only by the substitution of D-leucine for D-phenylalanine as one of the amino acid fragments inthe cyclic portion of the structure. Wilkinson and Lowehave corroborated the structure and have shown that colistinA is identical with polymyxin E1.
  Two forms of colistin have been prepared, the sulfate andmethanesulfonate, and both forms are available for use in theUnited States. The sulfate is used to make an oral pediatricsuspension; the methanesulfonate is used to make an intramuscularinjection. In the dry state, the salts are stable, andtheir aqueous solutions are relatively stable at acid pH from 2to 6. Above pH 6, solutions of the salts are much less stable.

• 위험도

  A poison by ingestion.

• Pharmaceutical Applications

  Polymyxin B and colistin (polymyxin E); mixtures of sulfates of polypeptides produced by strains of B. polymyxa and B. polymyxa var. colistinus. Colistimethate sodium (colistin sulfomethate sodium). Molecular weights: polymyxin B ₁ 1203; polymyxin B ₂ 1189; colistimethate sodium 1748.
  A group of basic polypeptide antibiotics with a side chain terminated by characteristic fatty acids. Five polymyxins (A–E) were originally characterized and others have since been added. Polymyxin B and colistin (polymyxin E) sulfates have been commercially developed.
  By treatment with formalin and sodium bisulfite, five of the six diaminobutyric acid groups of the polymyxins can be modified by sulfomethyl groups to form undefined mixtures of the mono-, di-, tri-, tetra- and penta-substituted derivatives. Sulfomethyl polymyxins differ considerably in their properties from the parent antibiotics: they are less active antibacterially, less painful on injection, more rapidly excreted by the kidney and less toxic. Only colistimethate sodium is now commercially available for systemic use, but polymyxin B and colistin sulfates are found as ingredients of several topical formulations.

• Clinical Use

  Colistimethate sodium
  Infections due to Ps. aeruginosa and other Gram-negative rods resistant to less toxic agents
  Cystic fibrosis (inhalation therapy for pseudomonas infection)
  Polymyxin B and colistin sulfate
  Component of preparations for local application
  Superficial infections with Ps. aeruginosa and to prevent the colonization of burns
  Selective decontamination of the gut and as a paste for control of upper respiratory tract colonization in patients on prolonged mechanical ventilation (in combination with other agents)

• Safety Profile

  A poison by ingestion, intraperitoneal, subcutaneous, and intravenous routes. When heated to decomposition it emits toxic vapors of NOx and SOx.

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