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
Dosing
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
1 MIU = 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
Safety
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