Colistin, Sulfat (Salz) Chemische Eigenschaften,Einsatz,Produktion Methoden
R-Sätze Betriebsanweisung:
R25:Giftig beim Verschlucken.
S-Sätze Betriebsanweisung:
S45:Bei Unfall oder Unwohlsein sofort Arzt zuziehen (wenn möglich, dieses Etikett vorzeigen).
Chemische Eigenschaften
White or almost white, hygroscopic powder.
Verwenden
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.
Acquired resistance
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.
Allgemeine Beschreibung
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.
Hazard
A poison by ingestion.
Pharmazeutische Anwendungen
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)
Sicherheitsprofil
A poison by ingestion,
intraperitoneal, subcutaneous, and
intravenous routes. When heated to
decomposition it emits toxic vapors of NOx
and SOx.
Colistin, Sulfat (Salz) Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
