Colistin: Difference between revisions
From IDWiki
(→) |
No edit summary |
||
| Line 9: | Line 9: | ||
*Also bind lipid A in the cell wall lipopolysaccharide |
*Also bind lipid A in the cell wall lipopolysaccharide |
||
===Resistance=== |
===Mechanisms of Resistance=== |
||
*Conferred by alterations in lipid A, either reducing its charge or eliminating it altogether |
*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) |
*May be chromosomal (e.g. pmrC, pmrF, pmrAB, lpxA, lpxC, lpxD, OprH) or plasmid-mediated (e.g. mcr-1 gene) |
||
*Often seen in ''[[Proteus species|Proteus]]'', ''[[Providencia species|Providencia]]'', ''[[Serratia species|Serratia]]'', ''[[Morganella species|Morganella]]'', ''[[Burkholderia species|Burkholderia]]'', ''[[Neisseria species|Neisseria]]'', and ''[[Brucella species|Brucella]]'' |
|||
=== Spectrum of Activity === |
|||
* Broadly active against Gram-negatives |
|||
* Not active against Gram-positives |
|||
* Resistance often seen in: |
|||
** ''[[Brucella species|Brucella]]'' |
|||
** ''[[Burkholderia species|Burkholderia]]'' |
|||
** [[Inquilinus limosus]] |
|||
** [[Morganellaceae]] (''[[Proteus species|Proteus]]'', ''[[Providencia species|Providencia]]'', ''[[Morganella species|Morganella]]'') |
|||
** ''[[Neisseria species|Neisseria]]'' |
|||
** [[Pandoraea]] |
|||
** ''[[Serratia species|Serratia]]'' |
|||
==Dosing== |
==Dosing== |
||
Revision as of 16:08, 21 August 2020
- 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
Mechanism of Action
- 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
- Broadly active against Gram-negatives
- Not active against Gram-positives
- Resistance often seen in:
Dosing
- 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
Adverse Effects
- Prominent and common nephrotoxicity, which is dose-related and usually reversible
- Rarely, neuromuscular blockage, which can cause weakness and apnea
