Guidelines
Polymyxin B & Colistin Dosing

Polymyxin B & Colistin Dosing

General Principles

  • Polymyxin B & Colistin (Polymyxin E) are polypeptide antibiotics that were first used clinically in the late 1950s, but fell out of favor due to high toxicity rates
  • Use of these compounds experienced a surge due to the need for antibiotics with activity against multi-drug resistant (MDR) Gram negatives (GN)
  • With the addition of newer antimicrobials for MDR GN infections and updated Clinical and Laboratory Standards Institute (CLSI) breakpoints to reflect lack of sensitivity, these agents are strongly discouraged when alternative agents are available

Antibacterial Activity:

  • Possible 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 as soon as possible

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 conversion to colistin

Risk of Nephrotoxicity:

  • Potentially nephrotoxic

Renal Dose Adjustment:

  • Required (CMS eliminated renally)

Antibacterial Activity:

  • Possible 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 as soon as possible

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

  • Per the CLSI, polymyxins are strongly discouraged for use when alternative agents are available; clinical and PK/PD data show limited clinical efficacy of polymyxins, even when organisms return intermediate
  • If utilized, a polymyxin should not be used as monotherapy and always in combination with one or more active agents

For all GN organisms, including Acinetobacter, Enterobacterales, and Pseudomonas:

  • ≤ 2 mcg/mL = intermediate
  • ≥ 4 mcg/mL = resistant
  • No breakpoints exist for sensitive organisms
  • Since disk diffusion testing via Kirby Bauer is no longer recommended via the CLSI, our Scripps micro lab will no longer perform on-site susceptibility testing
  • Tests will be sent out to a lab that can perform microbroth dilution to result in an MIC

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
  • Polymyxin B is available in vials of 500,000 units each (10,000 units = 1 mg)
    • Dilute all doses in 100 mL D5W or NS and administer LD over 2 hours and MD over 1 hour
  • Colistimethate Sodium (CMS) is available in vials equivalent to 150 mg of colistin base activity
    • Dilute in 50 mL D5W or NS and administer over 30 minutes
  • Dosing based on colistin base activity (use IBW, adjusted BW for obese)
  • Loading dose: 5 mg/kg (max 300 mg) x 1 for all patients
  • Maintenance dose:
    • CrCl ≥ 50 ml/min: 1.67 mg/kg IV Q8h
    • CrCl 30‐49 ml/min: 1.75 mg/kg IV Q12h
    • CrCl 10‐29 ml/min: 1.25 mg/kg Q12
    • CrCl < 10 ml/min: 1.5 mg/kg Q24h
    • HD: 1.5 mg/kg Q24h
    • CRRT: 1.67 mg/kg Q8
    • Maintenance dose to begin on interval patient is dosed
  • Use TBW, adjusted BW for obese
  • Loading dose: 2.5 mg/kg TBW (max 300 mg) x 1
  • Maintenance dose:
    • 1.25 mg/kg TBW (max 300 mg) Q12H
    • Limited data if HD or CRRT; no dosing adjustment suggested
    • Maintenance dose to commence 12 hrs after loading

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.