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Colistin Dosing Calculator – multi-drug-resistance option

Colistin Dosing Calculator (Beta)


Colistin, also known as polymyxin E, is a mixture of the cyclic polypeptides colistin A and B and belongs to the class of polypeptide antibiotics known as polymyxins. Colistin is effective against most Gram-negative bacilli. It remains one of the last-resort antibiotics for multidrug-resistant Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter.
Age:    Scr:    more info
(Scr) currently stable?:   | Restrict maximum CrCl: 
Gender:   Height:      Weight:

Colistin Dosing Factors 1,2,3

Colistin targeted average steady
state serum concentration (Css):
 
The desired Css should be based on the MIC for the target
organism(s), and the site and severity of the infection. Highly resistant organisms in critical care patients: Usual target: 3.5 mg/L (possibly higher).  Nephrotoxic effects can occur much more frequently at dosages that exceed 5mg/kg - monitor closely.		 Restrict the maximum calculated daily dose to the following:

 
Latest guidelines seem to point to a maximum dose of 475mg1

Background info

Clearance equations:
Cockcroft and Gault equation - utilizes actual body weight:
Male: CrCl (ml/min) = (140 - age) x wt (kg) / (serum creatinine x 72)
Female: Multiply above result by 0.85

Reference:
Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976;16(1):31-41.
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The original Cockcroft and Gault equation utilized total body weight, however, the most commonly used version of this equation incorporates the Ideal body weight (IBW).

Male: CrCl (ml/min) = (140 - age) x IBW (kg) / (serum creatinine x 72)
Female: Multiply above result by 0.85

Ideal body weight (IBW):
IBW (males) = 50 kg + 2.3 x (height [inches] - 60)
IBW (females) = 45.5 kg + 2.3 x (height [inches] - 60)
Reference:
Devine BJ. Gentamicin therapy. DICP. 1974; 8:650–5.

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Jelliffe equation - normalized for BSA:
Male: (98 - (0.8 * (age - 20)) / (SCR in mg/dL)) x 1.73 M2/Patient’s BSA
Female: Multiply above result by 0.9

References:
Jelliffe RW. Estimation of creatinine clearance when urine cannot be collected. Lancet 1971;1:975-6.
Jelliffe RW. Creatinine clearance: Bedside estimate. Ann Inter Med. 1973; 79:604.

Body Surface Area (BSA):
Program uses the following equation:
(Weight) kg0.425 x   (Height) cm0.725 x  0.007184 = BSA in M2

Reference: 
DuBois D, DuBois DF. A formula to estimate the approximate surface area if height and weight be known. Arch Int Med 1916;17:863-71.


Normalized CrCl (ml/min/1.73m2) = CrCl (ml/min) x 1.73/BSA4

Colistin dosing:1,2
Loading dose (mg) = colistin Css,avg target x 2.0 x body wt (kg).  [Use the lower of ideal or actual body weight, expressed in kg. ]

Maintenance dose (mg):  Daily dose = colistin Css,avg target  x (1.50 x CrCLn + 30).1,2
  • Divide dose and give q12h.
  • Maximum daily dose: 475mg
  • Colistin Css,avg target expressed in mg/L.
  • Creatinine clearance (CrCL) expressed in ml/min/1.73 m2 (normalized value). Although the Jelliffe equation was used to estimate CrCL in this study, other means (e.g., Cockcroft and Gault equation) may be used to estimate CrCL which would then be normalized to a body surface area of 1.73 m2.2
  • Package insert:
    CrCl geq80 mL/min: 2.5 - 5 mg/kg/day IV in 2 to 4 divided doses.
    CrCl 50-79 mL/min: 2.5-3.8 mg/kg/day IV divided q12hr
    CrCl 30-49 mL/min: 2.5 mg/kg/day IV q24h or divided q12hr
    CrCl 10-29 mL/min: 1.5 mg/kg IV q36hr

  

Colistin References
  1. Auwaerter, PG. Colistin: Optimal Dosing and Outcomes? Medscape Infectious Diseases © 2012 WebMD, LLC (Dec 03, 2012).  https://www.medscape.com/viewarticle/775212. Accessed: July 2014.

  2. Garonzik SM, Li J, Thamlikitkul V, et al. Population pharmacokinetics of colistin methanesulfonate and formed colistin in critically ill patients from a multicenter study provide dosing suggestions for various categories of patients. Antimicrob Agents Chemother. 2011;55:3284-3294.
    Suggested loading dose and daily maintenance doses of CMSa
    Source:  Garonzik SM, et al.
    Dose

    Category of critically ill patient
    Dosing
    suggestions
    Loading dose All patient categories Equation 9:    Loading dose of CBA (mg) = colistin Css,avg targetb x 2.0 x body wt (kg).c See caveat in footnote c. First maintenance dose should be given 24 h later.
    Maintenance dose Not on renal replacement Equation 10: Daily dose of CBA (mg) = colistin Css,avg targetb x (1.50 x CrCL + 30).d    
    Recommended dosage intervals based on CrCL:
    <10 ml/min/1.73 m2, every 12 h,
    10-70 ml/min/1.73 m2 every 12 (or 8) h, and
    >70 ml/min/1.73 m2 every 12 (or 8) h.
    See important caveat in footnote d.
      Receiving intermittent hemodialysis Daily dose of CBA on a non-HD day to achieve each 1.0-mg/liter colistin Css,avg targetb = 30 mge.  
    Supplemental dose of CBA on a HD dayf: add 50% to the daily maintenance  dose if the supplemental dose is administered during the last hour of the HD session, or add 30% to the daily maintenance dose if the supplemental dose is administered after the HD session. Twice-daily dosing is suggested.
      Receiving continuous renal replacement Daily dose of CBA to achieve each 1.0-mg/liter colistin Css,avg target = 192 mg.g     Doses may be given every 8-12 h.
    1. Expressed as mg of colistin base activity (CBA) for various categories of critically ill patients. The suggested maintenance daily dose would commence 24 h after administration of a CMS loading dose. Example: To target a colistin Css,avg of 2.5 mg/liter, a 55-kg patient with a CrCL of 40 ml/min/1.73 m2 would receive a loading dose of 275 mg CBA followed in 24 h by commencement of a maintenance regimen of 225 mg CBA/day in 2 to 3 equally divided doses.
    2. Colistin Css,avg target is expressed in mg/liter. This target should be based on MIC, site, and severity of infection.
    3. Use the lower of ideal or actual body weight, expressed in kg. At this time, we suggest caution in the use of a loading dose greater than 300 mg CBA (see the text for more details).
    4. Based upon the population PK analysis for 101 critically ill patients not on continuous renal replacement therapy. Colistin Css,avg target expressed in mg/L.Creatinine clearance (CrCL) expressed in ml/min/1.73 m2. Although the Jelliffe equation was used to estimate CrCL in this study, other means (e.g., Cockcroft and Gault equation) may be used to estimate CrCL which would then be normalized to a body surface area of 1.73 m2. See text for caveat regarding use of the algorithm in patients with CrCL values > 70 ml/min/1.73 m2 or when targeting a “high” colistin Css,avg, both being circumstances where the algorithm may predict daily doses of CBA substantially greater than the current upper limit in the product label.
    5. Based upon use of equation 10 and setting CrCL to zero.
    6. Supplemental dose of CMS to achieve a similar colistin Css,avg on a HD day as occurs on a non-HD day. It is assumed that the hemodialysis session occurs toward the end of a CMS dosage interval.
    7. Based on the population PK analysis for 4 critically ill patients receiving continuous renal replacement therapy.

  3. Gilbert DN, Chambers HF, Eliopoulos GM. The Sanford Guide To Antimicrobial Therapy 2014. 44th ed. Sperryville: Antimicrobial Therapy; 2014.
  4. Murphy JE. Estimating Creatinine Clearance. In: Murphy JE, ed. Clinical Pharmacokinetics, 4th ed. Bethesda, MD: American Society of Health-System Pharmacists, 2008:(4).
Colistin Dosing Calculator – multi-drug-resistance option

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