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Serious Medicine. Extraordinary Care.

Colistin

Restrictions and Dosing Guidelines

Colistin is a polymyxin E antibiotic administered as the prodrug colistimethate which was originally introduced in the late 1950’s.1 Colistin’s association with adverse effects including nephrotoxicity and neurotoxicy led to a decline in use. 2,3 Recently there has been a resurgence in colistin use driven by the increasing prevalence of difficult-to-treat multi-drug resistant Gram-negative pathogens (e.g. P. aeruginosa, Acinetobacter sp., and carbapenem-resistant Enterobacteriaceae).

Best practices for colistin dosing are unclear. The initial experiences with colistin occurred before the advent of modern pharmacokinetics, pharmacodynamics, and toxicodynamics. Thus, only limited data on the optimal dosing of colistin exists.4-7 To complicate the matter, the FDA-approved labeling is for colistimethate for injection (prodrug), but the product is typically dosed according to colistin base activity. This often leads to confusion in clinical practice and represents a potential for medication errors as highlighted a recent alert from the National Coordinating Council on Medication Error Reporting and Prevention. 8

Due to the unique place colistin holds in the antibiotic armamentarium as salvage therapy for patients infected with multi-drug resistant Gram-negative pathogens, the complexities of dosing and significant toxicity risk, the following recommendations to its use are recommended:

Restrictions:

  1. Colistin use will be restricted to Infectious Disease and Pulmonary physicians
    1. Applies to both intravenous and inhaled formulations
    2. Use by other services requires formal consultation by Infectious Disease or Pulmonary
      1. The drug will be distributed for 24 hours only unless one of those groups has been formally consulted and approved the use
  2. All colistin orders must be ordered as “colistin” or “colistin base”
  3. Orders for colistimethate or colistimethate sodium must be clarified by pharmacy and reordered in terms of colistin base
  4. Example: Colistin base 5 mg/kg/day IV divided q8h

Suggested Dosing Guidelines6, 11

  1. Intravenous with normal renal function:
    1. Colistin base 5 mg/kg/day IV divided q8h or q12h
    2. Calculate dose using lesser of actual or ideal body weight
  2. Intravenous with abnormal renal function (CrCl <=40 ml/min)
    1. Maintenance dose and dosing interval should be based on the renal dosing protocol
    2. A load of 2.5 mg/kg IV q12h x2doses should be given to all patients with a creatinine clearance (CrCl) of <= 40 ml/min (the loading doses are not renally adjusted)
    3. Subsequent maintenances doses should begin 24 hours after the first loading dose
      1. CrCl >40: No adjustment necessary
      2. CrCl 20-40: 75% of total daily dose IV divided q12h
      3. CrCl 10-19: 50% of total daily dose IV divided q12h
      4. CrCl <10, intermittent hemodialysis, or peritoneal dialysis: 50 mg IV q12h
        1. Administered after dialysis on dialysis days
        2. In pediatric patients use 1.5 mg/kg/day divided q12h
    4. Sustained low-efficiency dialysis (SLED)
      1. While on SLED dose as CrCl>40
      2. While off SLED dose as CrCl<10
  3. Dosing, inhalation:7, 9, 10 Inhaled colistin base should not be used as pneumonia monotherapy and should be combined with an IV antimicrobial agent. IV colistin base can be used in conjunction with inhaled colistin base given inhaled colistin is not systemically absorbed.
    1. Adults: 75 mg or 150 mg colistin base inhaled q12h
    2. Children <13 years of age: 30 mg or 75 mg colistin base inhaled q12h

References:

  1. Lim L, et al. Pharmacotherapy 2010;30(12):1279–1291)
  2. Hartzell JD, et al. Clin Infect Dis. 2009 Jun 15;48(12):1724-8.
  3. Molina J, et al. Expert Opin Pharmacother 2009;10:2811–28.
  4. Markou N, et al. Clin Ther. 2008 Jan;30(1):143-51.
  5. Plachouras D, et al. Antimicrob Agents Chemother. Aug. 2009, p. 3430–3436
  6. Garonzik SM, et al. Antimicrob Agents Chemother. 2011 Jul;55(7):3284-94.
  7. Ratjen F, et al. J Antimicrob Chemother 2006; 57: 306–311
  8. http://www.ashp.org/DocLibrary/Policy/PatientSafety/NANAlert-Colistimethatesodium.aspx
  9. Rattanaumpawan P, et al. J Antimicrob Chemother 2010; 65: 2645–2649
  10. Kofteridis DP, et al. Clinical Infectious Diseases 2010; 51(11):1238–1244
  11. Monarch Pharmaceuticals, Inc. 5/2009. Colistimethate. Package Insert. Monarch Pharmaceuticls, Inc. Bristol, TN
  12. March 2012