Stanford Antimicrobial Safety and Sustainability Program

Revision date 3/2022

Stanford Medication Usage Guide

Polymyxin B & Colistin

What: Polymyxin B is preferred over Colistin (polymyxin E) for non-urinary infections due to multidrug
resistant gram-negative bacilli at Stanford Health Care.

SHC formulary restriction criteria – Polymyxin B

1. Infectious Disease Consultation and ID recommendation for use
2. Cystic Fibrosis team
SHC formulary restriction criteria – Colistin
1. Treatment of urinary tract infections
2. Inhalation route

Why: Polymyxin B and Colistin (polymyxin E) have the same spectrum of activity. However, Polymyxin
B has favorable clinical pharmacologic properties compared to Colistin
o Polymyxin B is an active drug that is minimally excreted in urine, whereas Colistin is
excreted in the urine as the prodrug colistimethate sodium (CMS). CMS is converted in
vivo and has variable and slow (hours) conversion to the active moiety; lower renal
clearance allows more time for this conversion to occur, leading to higher levels of active
drug.
o Polymyxin B may be less nephrotoxic

How: Polymyxin B and Colistin dosing is NOT interchangeable

o Polymyxin B is usually dosed by “unit”, not “mg”
o Note that with Polymyxin B, each 500,000 units is diluted in 300-500mL: a typical dose
may result in 1L of fluid
o Caution with colistin MIC ≥ 2; CLSI has no established MIC breakpoint for susceptible;
MIC breakpoint for intermediate is ≤2 for Enterobacterales, P.aeruginosa, and
Acinetobacter spp.
o For severe infections, colistin and polymyxin B should be used in combination with other
ABX. Treatment guidance from IDSA (link 1, link 2)

Monitoring: Neurotoxicity
o May occur in 1st few days of therapy and may be dose or infusion-rate dependent. May
include dizziness, muscle weakness, confusion, headache, visual disturbances, ataxia,
paresthesias.
o Mild ADEs are usually benign and reversible upon discontinuing polymyxin
o Management: slow the infusion, lower the dose
 Stanford Antimicrobial Safety and Sustainability Program
Revision date 3/2022

Dosing
IHD
Route Dosing
CRRT
Polymyxin B 20,000 to 25,000 units/kg loading dose, followed by
Use actual body weight; IV 12,500 units/kg IV Q12H; No dose adjustment needed
adjusted body wt for
obese caution with single doses > 2,000,000 units
Preferred Dosing for Critically Ill Patients (Consult ID 300mg CBA load followed by
Pharmacist) 180mg CBA on either HD
days or 130mg CBA on
Suggested loading dose and daily doses of colistimethate for nondialysis days
desired target colistin Css,avg of 2 mg/L

CrCl Dosing Regimen

Loading
300 mg CBA x 1
Dose
> 90 mL/min 180 mg q12h
80 – 89 mL/min 170 mg q12h
Colistin IV
Use ideal body weight 70 – 79 mL/min 150 mg q12h
60 – 69 mL/min 138 mg q12h 300mg CBA load followed by
Doses expressed in
colistin base activity 50 – 59 mL/min 122 mg q12h 220mg CBA Q12H
(CBA) Maintenance
40 – 49 mL/min 110 mg q12h
Dose
30 – 39 mL/min 98 mg q12h
20 – 29 mL/min 88 mg q12h
10 – 19 mL/min 80 mg q12h
5 – 9 mL/min 72 mg q12h
0 mL/min 65 mg q12h

Inhalation 150 mg inhalation Q12H

Conversions:
Colistimethate sodium 1 mg = ~12,500 units of colistimethate sodium
Colistimethate sodium ~2.67 mg = 1 mg of colistin base activity
1 mg colistin base activity (CBA) = 30,000 IU colistin
1 mg polymyxin B = 10,000 IU polymyxin B

Document Information:
A. Original Author/Date: Lina Meng, PharmD, BCPS, BCCCP, Emily Mui, PharmD, BCPS,
Stan Deresinski, MD, 02/2015
B. Gatekeeper: Antimicrobial Stewardship Program
C. Review and Renewal Requirement
This document will be reviewed every three years and as required by change of law or
practice
D. Revision/Review History: 11/2017, 3/2022
E. Approvals
1. Antimicrobial Subcommittee: 11/2017, 3/2022
2. P&T: 12/2017, 4/2022 pending
 Stanford Antimicrobial Safety and Sustainability Program
Revision date 3/2022

References:

1. Micromedex online, accessed 2/17/2016, Lexicomp online, accessed 12/20/2021

2. Falagas ME, Kasiakou SK. Toxicity of polymyxins: a systematic review of the evidence from old and recent studies. Critical
care. 2006 Feb 13;10(1):R27.
3. Nelson, Brian C., et al. "Clinical outcomes associated with polymyxin B dose in patients with bloodstream infections due to
carbapenem-resistant Gram-negative rods." Antimicrobial agents and chemotherapy 59.11 (2015): 7000-7006.
4. Pai MP. Polymyxin B dosing in obese and underweight adults. Clin Infect Dis 2013;57:1785.
5. Rigatto, Maria Helena, et al. "Renal failure in patients treated with colistin versus polymyxin B: a multicenter prospective cohort
study." Antimicrobial Agents and Chemotherapy (2016): AAC-02634.
6. Rigatto, Maria Helena, et al. "Clinical features and mortality of patients on renal replacement therapy receiving polymyxin B."
International journal of antimicrobial agents (2015).
7. Rigatto, Maria Helena, et al. "Risk factors for acute kidney injury (AKI) in patients treated with polymyxin B and influence of AKI
on mortality: a multicentre prospective cohort study." Journal of Antimicrobial Chemotherapy (2015): dku561.
8. Sandri, Ana M., et al. "Population pharmacokinetics of intravenous polymyxin B in critically ill patients: implications for selection
of dosage regimens." Clinical infectious diseases 57.4 (2013): 524-531.
9. Sandri, Ana M., et al. "Pharmacokinetics of polymyxin B in patients on continuous venovenous haemodialysis." Journal of
Antimicrobial Chemotherapy (2012): dks437.
10. Zavascki, Alexandre P., et al. "Pharmacokinetics of intravenous polymyxin B in critically ill patients." Clinical infectious diseases
47.10 (2008): 1298-1304.
11. Tsuji BT, Pogue JM, Zavascki AP, et al. International Consensus Guidelines for the Optimal Use of the Polymyxins: Endorsed
by the American College of Clinical Pharmacy (ACCP), European Society of Clinical Microbiology and Infectious Diseases
(ESCMID), Infectious Diseases Society of America (IDSA), International Society for Anti-infective Pharmacology (ISAP),
Society of Critical Care Medicine (SCCM), and Society of Infectious Diseases Pharmacists (SIDP). Pharmacotherapy 2019;
39(1): 10-39.
12. Table 2A. Zone Diameter and MIC Breakpoints for Enterobacterales, Table 2B-1. Zone Diameter and MIC Breakpoints for
Pseudomonas aeruginosa, Table 2B-2. Zone Diameter and MIC Breakpoints for Acinetobacter spp. CLSI M100-ED31:2021
Performance Standards for Antimicrobial Susceptibility Testing, 31st Edition
13. Nation RL, Garonzik SM, Thamlikitkul V, et al. Dosing guidance for intravenous colistin in critically-ill patients. Clin Infect Dis.
2017;64(5):565-571. doi:10.1093/cid/ciw839[PubMed 28011614]

Summary of changes:

3/1/2022:
• Migrated colistin dosing info from ABX Dosing card to SMUG
• Added CLSI info on new breakpoints
• Updated PolyB dosing
• Added explanation of polymyxin B’s vs Colistin’s PK and activity in urine