From IDWiki


  • A member of the polymyxin class also known as polymyxin E
  • Administered intravenously as a prodrug, colistin methanesulphonate (CMS), or orally and topically as colistin sulfate
  • Active against most Gram-negative bacteria
  • Currently reserved for multidrug-resistant Gram-negative infections, including resistant Pseudomonas aeruginosa, Acinetobacter baumannii, and carbapenem-resistant Enterobacterales

Mechanism of Action

  • Given as a prodrug, which is converted in vivo into the active drug (compared to polymixin B, which is given in its active form)
  • Disrupt membranes by interacting with membrane phospholipids to displace divalent cations
  • Also bind lipid A in the cell wall lipopolysaccharide

Mechanisms of Resistance

  • Conferred by alterations in lipid A, either reducing its charge or eliminating it altogether
  • May be chromosomal (e.g. pmrC, pmrF, pmrAB, lpxA, lpxC, lpxD, OprH) or plasmid-mediated (e.g. mcr-1 gene)

Spectrum of Activity

Pharmacokinetics and Pharmacodynamics

  • Distribution:
    • CMS is about 50% protein bound
    • Distributes well into liver, kidney, heart, and muscle
    • Poor distribution into bones, cerebrospinal fluid, lung parenchyma, and pleural cavity
  • Metabolism: Can take up to 36 hours to achieve steady state colistin during administration of CMS
  • Elimination:
    • Two-thirds of CMS is eliminated unchanged by the kidneys
    • Colistin is cleared by unknown non-renal and non-biliary routes
  • Concentration-dependent activity

Clinical Breakpoints

Species ECV (μg/mL) Breakpoints (μg/mL) Breakpoints (mm)
Acinetobacter baumannii complex ≤2 ≥4


Dosing Equivalents

  • Dosing is a mess, with a number of different units used by different people, despite having a standardized international unit, usually in millions (MIU)
    • 1 MIU = 80 mg colistimethate (CMS) in Europe = 30 mg colistin base activity (CBA) in the US
    • 1 mg of CMS = 0.375 mg of colistin base activity = 12,500 IU
    • 1 mg of colistin base activity = 2.6 mg of CMS = 32,500 IU
  • IU is used in Europe while CBA is used in the US

Intravenous Dosing

  • For European dosing, using IU of CMS:
    • Weight ≤60 kg: 50-75 kIU/kg/day divided q8h
    • Weight >60 kg: 1-2 MIU q8h, dose-adjusted to q12-18h for CrCl 10-20 and q18-24h for CrCl <10
  • For US dosing, using mg of CBA:
    • 2.5-5 mg/kg ideal body weight daily divided q12h to q6h
    • E.g. 300 mg CBA (10 IU) daily for a 60 kg patient, compared to 3 to 4.5 MIU daily in Europe
  • Critically ill patients may benefit from a loading dose of 300 mg CBA followed by regular maintanance dosing in 12 to 24 hours
  • Per Mandell:
    • 5 mg CBA/kg IBW as loading dose (max 300 mg) followed by 5 mg CBA/kg IBW daily divided q8h
    • Maintenance is renally adjusted to 3.5 mg/kg/day divided q12h for CrCl 30-49, 2.5 mg/kg/day divided q12h for CrCl 10-29, and 1.5 mg/kg q24h for CrCl <10 or hemodialysis

Intrathecal Dosing

  • Exists.

Inhalational Dosing

  • CMS is dissolved in 4–6 ml of normal saline or sterile water and given by nebulizer
    • Results in low systemic levels
  • Body weight <40 kg: 0.5 MIU (40 mg) of CMS every 12 h
  • Body weight >40 kg: 1.0 MIU (80 mg) of CMS every 12 h
  • For recurrent or severe pulmonary infection: 2.0 MIU (160 mg) of CMS every 8 h

Renal Dosing

  • Serum creatinine level 115 to 132 μmol/L: 2 MIU (160 mg) of CMS every 8 h
  • Serum creatinine level 141 to 221 μmol/L: 2 MIU (160 mg) of CMS every 12 h
  • Serum creatinine level ≥230 μmol/L: 2 MIU (160 mg) of CMS every 24 h
  • Hemodialysis: 2 MIU (160 mg) of CMS after each hemodialysis
  • Peritoneal dialysis: 2 MIU (160 mg) of CMS daily during peritoneal dialysis
  • Continuous renal replacement therapy (CRRT): high loading dose followed by a maintenance dose of up to 4.5 MIU every 8 h
    • Continuously eliminated, and needs higher dosing


Adverse Effects

  • Prominent and common nephrotoxicity, which is dose-related and usually reversible
  • Rarely, neuromuscular blockage, which can cause weakness and apnea
  • Other neurological effects include peripheral paresthesia, tingling of tongue, dizziness, vertigo, blurred vision, slurred speech, ataxia

Further Reading

  • International Consensus Guidelines for the Optimal Use of the Polymyxins. Pharmacotherapy. 2019;39(1):10-39. doi: 10.1002/phar.2209
  • Colistin for lung infection: an update. J Intensive Care. 2015;3(1):3. doi: 10.1186/s40560-015-0072-9