Guidelines
Polymyxin B & Colistin Dosing

Polymyxin B & Colistin Dosing

General Principles

  • Polymyxin B & Colistin (Polymyxin E) are polypeptide antibiotics first used in the late 1950s, but fell out of favor due to toxicities
  • Use of these compounds has increased with the advent of MDR Gram-negative organisms but should be reserved as last-line agents as clinical efficacy is limited, and toxicities are high

Antibacterial Activity:

  • Activity against MDR Pseudomonas, Acinetobacter and Enterobacterales
  • Cross‐resistance exists with Polymyxin B

Administered As:

  • Inactive prodrug colistimethate sodium (CMS) and has variable and slow conversion to active moiety

Loading Doses:

  • Required to achieve therapeutic plasma concentrations sooner

Clearance:

  • CMS primarily cleared in urine, where a portion of CMS is converted to active colistin
  • High interindividual variability in colistin clearance

Attainment of Therapeutic Concentrations:

  • Difficult to achieve in patients with normal renal function as only ~20% of CMS is converted to colistin

Risk of Nephrotoxicity:

  • Potentially nephrotoxic

Renal Dose Adjustment:

  • Required (CMS eliminated renally)

Antibacterial Activity:

  • Activity against MDR Pseudomonas, Acinetobacter and Enterobacterales
  • Cross‐resistance exists with colistin

Administered As:

  • Active Drug; has favorable clinical pharmacologic properties since not a prodrug like colistin

Loading Doses:

  • Required to achieve therapeutic plasma concentrations sooner

Clearance:

  • Extensively reabsorbed, leading to low polymyxin B concentrations in urine

Attainment of Therapeutic Concentrations:

  • Since active drug administered, it is possible to achieve desired plasma concentrations

Risk of Nephrotoxicity:

  • Potentially nephrotoxic

Renal Dose Adjustment:

  • Not Required

Susceptibility Testing

Warning

Notably, CLSI no longer provides susceptible interpretations owing to lack of clinical efficacy

For all GN organisms, including Acinetobacter baumannii complex, Enterobacterales and Pseudomonas aeruginosa:

  • ≤ 2 mcg/mL = intermediate
  • ≥ 4 mcg/mL = resistant
  • No breakpoints exist for sensitive organisms
  • Scripps Microbiology no longer performs in-house disk diffusion for these agents, testing is sent to ARUP

Treatment

  • Polymyxin B is preferred over colistin for all MDR‐GNB systemic infections outside of the urinary tract due to more predictable pharmacokinetics
  • Exception: colistin is preferred over polymyxin B for
    • Urinary tract infections
    • Nebulization administration
    • Intrathecal/intraventricular administration
  • Polymyxin B and colistin dosing is NOT interchangeable
  • Available in vials equivalent to 150 mg of colistin base activity (CBA)
  • Dosing based on CBA
  • Loading dose: 300 mg IV x 1, then begin IV maintenance dose 12 hours after load
  • Maintenance dose:
    • CrCl ≥ 90 ml/min: 180 mg q12h
    • CrCl 80-89 ml/min: 170 mg q12h
    • CrCl 70-79 ml/min: 150 mg q12h
    • CrCl 60-69 ml/min: 135 mg q12h
    • CrCl 50-59 ml/min: 120 mg q12h
    • CrCl 40‐49 ml/min: 110 mg q12h
    • CrCl 30‐39 ml/min: 100 mg q12h
    • CrCl 20-29 ml/min: 90 mg q12h
    • CrCl 10-19 ml/min: 80 mg q12h
    • CrCl 5-10 ml/min: 70 mg q12h
    • HD: Start maintenance dose 24 hours after load and doses are to be given every day with daily dose dependent on whether HD will occur that day (time dose in PM to ensure HD performed):
      • Non-HD days: 130 mg
      • HD days: 170 mg post-HD
    • CRRT: 220 mg q12h
  • Dilute all doses in 50 mL D5W or NS and administer over 30 minutes
  • Available in vials of 500,000 units = 50 mg each (10,000 units = 1 mg)
  • Use TBW, with max doses noted below
  • No renal dose adjustments are required, including for patients receiving IHD/CRRT
  • Loading dose: 2.5 mg/kg TBW (max 300 mg) IV x 1, then begin maintenance dose 12 hours after load
  • Maintenance dose: 1.25 mg/kg TBW (max 200 mg) IV q12h
  • Dilute all doses in 100 mL D5W or NS and administer loading dose over 2 hours and maintenance dose over 1 hour

More Information

  1. Nation RL, et al. Colistin and Polymyxin B: Peas in a Pod or Chalk and Cheese? Clin Infect Dis. 2014:59(1):88‐94.
  2. Akajagbor DS, et al. Higher incidence of acute kidney injury with intravenous colistimethate sodium compared with polymyxin B in critically ill patients at a tertiary care medical center. Clin Infect Dis. 2013 Nov;57(9):1300‐3
  3. Kwa, A et al. Polymyxin B: similarities to and differences from colistin (polymyxin E). Expert Rev Anti Infect Ther. 2007 Oct;5(5): 811‐21
  4. Kassamali Z et al. To B or not to B, that is the question: is it time to replace colistin with polymyxin B? Pharmacotherapy. 2015 Jan;35(1):17‐21.
  5. Micromedex.
  6. Kaye KS. (2015, September). Parenteral Use of Colistin (and Polymyxin B) in North America. In J. Li (Chair), The Polymyxin Jigsaw: More pieces put in place. Presentation conducted at the meeting of Polymyxins 2015, San Diego, CA.
  7. Gales AC, et al. Contemporary Assessment of Antimicrobial Susceptiblity Testing Methods for Polymyxin B and Colistin: Review of Available Interpretative Criteria and Quality Control Guidelines. J Clin Micirobiol 2001;39(1):183‐190.
  8. Galani I, et al. Colistin susceptibility testing by Etest and disk diffusion methods. Int J Antimicrob Agents 2008:31(5):434‐439.
  9. CLSI. Performance Standards for Antimicrobial Susceptibility Testing. 33 rd ed. CLSI supplement M100. Wayne PA; Clinical and Laboratory Standards Institute; 2020.
  10. Tsuji BT, et al. International Consensus Guidelines for the Optimal Use of Polymyxins. Pharmacotherapy. 2019 Jan;39(1):10-39.