Colistin sulfate

Colistin is a polypeptide antibiotic which inhibits gram-negative bacteria by binding to lipopolysaccharides and phospholipids in the outer cell membrane of gram-negative bacteria.

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> Anti-infection >> Bacterial

Research Areas >> Infection

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].

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].

[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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MOLECULAR FORMULA :

C45-H85-N13-O10.H2-O4-S

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

72200 ug/kg

TOXIC EFFECTS :

Lungs, Thorax, or Respiration - dyspnea Lungs, Thorax, or Respiration - cyanosis

REFERENCE :

KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 13,7,1979

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

793 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 11,395,1961

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

21800 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 11,395,1961

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

53500 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 11,395,1961

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

6 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

ABANAE Antibiotics Annual. (New York, NY) 1953-60. For publisher information, see AMACCQ. Volume(issue)/page/year: 7,41,1959/1960

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

58 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

NKRZAZ Chemotherapy (Tokyo). (Nippon Kagaku Ryoho Gakkai, 2-20-8 Kamiosaki, Shinagawa-Ku, Tokyo 141, Japan) V.1- 1953- Volume(issue)/page/year: 16,105,1968 *** REVIEWS *** TOXICOLOGY REVIEW ANBCB3 Antibiotics and Chemotherapy (Basel). (S. Karger AG, Postfach CH-4009 Basel, Switzerland) V.17- 1971- Volume(issue)/page/year: 31,119,1982 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - M4682 No. of Facilities: 215 (estimated) No. of Industries: 2 No. of Occupations: 6 No. of Employees: 2247 (estimated) No. of Female Employees: 1438 (estimated)