An antibiotic
Colistin sulfate is a polypeptide antibiotic which inhibits gram-negative bacteria by binding to lipopolysaccharides and phospholipids in the outer cell membrane of gram-negative bacteria.
Colistins are bactericidal to gram-negative bacteria by a detergent-like mechanism. This mechanism involves interaction with lipopolysaccharides and phospholipids of the outer membrane and electrostatic interference with the outer membrane by competitively displacing divalent cations (calcium and magnesium) from the negatively charged phosphate groups of membrane lipids[1]. Colistin (polymyxin E) owns favorable properties of rapid bacterial killing, a narrow spectrum of activity, and an associated slow development of resistance for the treatment of infections caused by multidrug-resistant gram-negative bacteria. There are two forms of colistin available commercially: colistin (sulfate) mainly for topical use and colistin methanesulfonate (sodium) for parenteral use[2].
High concentrations of colistin in rat ELF are achieved as a result of slow and sustained CMS conversion following i.t. instillation[3]. Colistin is often used in piglets but underdosing and overdosing are frequent. Under- or overdoses of colistin do not result in any major disturbance of piglet fecal microbiota and rarely select for chromosomal resistance in the dominant E. coli population[4].
参考文献:
[1]. Hancock RE et al. Peptide antibiotics. Antimicrob Agents Chemother. 1999 Jun;43(6):1317-23.
[2]. Li J, et al. In vitro pharmacodynamic properties of colistin and colistin methanesulfonate againstPseudomonas aeruginosa isolates from patients with cystic fibrosis. Antimicrob Agents Chemother. 2001 Mar;45(3):781-5.
[3]. W S Yapa S, et al. Population pharmacokinetics of colistin methanesulfonate in rats: achieving sustained lung concentrations of colistin for targeting respiratory infections. Antimicrob Agents Chemother. 2013 Oct;57(10):5087-95.
[4]. Fleury MA, et al. Impact of two different colistin dosing strategies on healthy piglet fecal microbiota. Res Vet Sci. 2016 Aug;107:152-60.
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Animal experiment: |
Rats: Colistin methanesulfonate (sodium) and colistin (sulfate) dosing solutions are freshly prepared in sterile 0.9% sodium chloride. For the i.v. studies, colistin methanesulfonate (CMS) or sulfate solutions are administered by a bolus injection via the jugular vein cannula. Intratracheal (i.t.) instillation is utilized as the technique for pulmonary administration. Animals are administered i.v. CMS at doses of 14 mg/kg of body weight, 28 mg/kg or 56 mg/kg. In an independent study, rats are administered i.v. colistin at doses of 0.21 mg/kg, 0.41 mg/kg, or 0.62 mg/kg[3]. |
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参考文献: [1]. Hancock RE et al. Peptide antibiotics. Antimicrob Agents Chemother. 1999 Jun;43(6):1317-23. |
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