Colistin

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Colistin (polymyxin E)

Two forms:

• Colistin sulfate administered enterally (for bowel decontamination) or topically for bacterial skin infections

• Colistimethate sodium administered intravenously, intramuscularly or by nebulization

Mechanism of action

Binds with anionic lipopolysaccharide molecules by displacing calcium and magnesium from outer cell membrane of gram negative bacteria. Results in leakage of cell contents and cell death

Colistimethate sodium

Pro-drug. Metabolized to colistin

Dosage & Administration

• IV/IM/nebulizer/(intrathecal0

• Intravenous

  • 2.5-5 mg/kg/day in 2-4 divided doses (US guidelines or
    4-6 mg/kg/day in 3 divided doses for patients ≤60 kg and 80-160 mg 8 hourly for heavier patients (UK guidelines)

  • Use of higher doses has been reported

• Nebulization: mixed in 4 ml saline. For patients ≤40 kg body weight give 40 mg 12hourly, for heavier patients 80 mg 12 hourly

• Few reports of intrathecal administration although this is not an approved route of administration

Elimination

Renal. Reduce dose in renal dysfunction

Pharmacodynamics

Concentration-dependent killing

Spectrum of activity

Gram negative aerobes including:

• Acinetobacter species

• Pseudomonas aeruginosa

• Klebsiella species

• Enterobacter species

• E. coli

• Citrobacter species

• Morganella morgani

• Salmonella

• Shigella

Not active against some Gram negative aerobes including Pseudomonas mallei, Burkholderia cepacia, Proteus species, Providencia species and Serratia species

Indications

• Infection with Gram negative bacteria (confirmed to be sensitive on in vitro testing) which are resistant to other available anti-microbials.

• Greater activity against P.aeruginosa, Salmonella spp and Shigella spp than polymyxin B

Adverse effects

• Renal (acute tubular necrosis). However renal toxicity may not be as great as previously thought

• Neurotoxicity:

  • Dizziness

  • Weakness

  • Facial parasthesia

  • Vertigo

  • Visual disturbances

  • Confusion

  • Ataxia

  • Neuromuscular blockade

Further reading 

Falagas ME, Kasiakou SK. Colistin: the revival of polymyxins for the management of multidrug-resistant Gram-negative bacterial infections. Clin Infectious Dis, 2005; 40:1333-41

©Charles Gomersall, October, 2009 unless otherwise stated. The author, editor and The Chinese University of Hong Kong take no responsibility for any adverse event resulting from the use of this webpage.
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