Colistin

A member of the polymyxin class also known as polymyxin E
Active against most gram-negatives except for Proteus species and several others (see Resistance, below)
Currently reserved for resistant Pseudomonas aeruginosa, Acinetobacter baumannii, and carbapenem-resistant Enterobacteriaceae

Background

Disrupt membranes by interacting with membrane phospholipids to displace divalent cations
Also bind lipid A in the cell wall lipopolysaccharide

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)
Often seen in Proteus, Providencia, Serratia, Morganella, Burkholderia cepacia, Neisseria, and Burcella

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
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
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

Prominent and common nephrotoxicity, which is dose-related and usually reversible
Rarely, neuromuscular blockage, which can cause weakness and apnea