1. DATA ANALYSIS
•Weight measures (i.e. IBW, ABW, LBW), renal clearance (using
Cockcroft-Gault, MDRD, and CKD-EPI equations) and patient-
specific PK values (e.g. ke, Vd, and Clvanc ) were determined for
each patient (n=239).
•All data were analyzed using SPSS 19.0 (Chicago, IL) with p-
value < 0.05 being statistically significant.
•Vancomycin Vd was normalized to all weight descriptors using
ANOVA with post-hoc comparisons via Bonferroni test.
•Ordinary least squares regression was used to compare renal
clearance between Cockcroft-Gault, MDRD, and CKD-EPI, as a
predictor of vancomycin clearance.
Life Beyond Cockcroft-Gault:
Is there a better method to optimize vancomycin dosing?
•••••
Elva Angelique Van Devender, Ph.D., Pharm.D., Ravina Kullar, Pharm.D., MPH, James Leggett, MD
Providence Health and Services • Portland, Oregon
BACKGROUND
•Vancomycin is the mainstay of treatment for complicated
Gram-positive resistant infections, such as methicillin-resistant
Staphylococcus aureus (MRSA).
•The most appropriate weight descriptor for dosing vancomycin
is unknown. Historically, vancomycin dosing has been based on
total body weight (TBW).
•Vancomycin clearance is typically assessed using the Cockcroft-
Gault equation. The utility of newer equations (the
Modification of Diet in Renal Disease (MDRD) equation and the
Chronic Kidney Disease-Epidemiology (CKD-EPI) equation) in
vancomycin dosing is unknown.
METHODS
PATIENT POPULATION
Inclusion criteria: Adult patients >18 years old with > 2 documented
vancomycin trough concentrations admitted to Providence St. Vincent
Medical Center and Providence Portland Medical Center from January-
October 2011.
Exclusion criteria: Patients with rapidly changing or unstable renal
function (SCr increase of > 0.5 from baseline or patients on hemodialysis).
DATA ABSTRACTED
•Patient demographics, height, weight, BMI, serum creatinine, length of
stay
•Vancomycin doses, trough levels, indication for therapy
CONCLUSIONS
•Trend toward TBW as the most accurate weight predictor (i.e.
least variable) in between weight categories to best estimate
vancomycin Vd (p > 0.567). IBW was the least accurate
predictor (i.e. most variable) in between weight categories in
predicting Vd (p < 0.023).
•Mean Vd= 0.47 L/kg in our study
•The Cockcroft-Gault equation using adjusted body weight
(ABW) was the method most closely correlated to vancomycin
clearance.
OBJECTIVES OF THE CURRENT STUDY
•To determine which weight parameter (e.g. TBW, IBW, LBW, or
ABW) best estimates vancomycin Vd
•To compare the Cockcroft-Gault, MDRD, and CKD-EPI
equations to determine which method is the most precise in
effectively dosing vancomycin
WHAT
THEY
DID
•Pai et. al. optimized the dosing of aminoglycosides by
evaluating a range of patient weights and various
renal function equations.
WHAT
THEY
FOUND
•LBW best estimated Vd
•CKD-EPI best predicted aminoglycoside clearance
LIMITATIONS
•Assumed vancomycin Cmax of 40 for each patient
•Small sample size; large percentage of Caucasian population
•Not all patients were at steady state
DISCLOSURES
All authors have nothing to disclose.
RESULTS
OBESITY CATEGORIES* (N=239) INDICATIONS FOR VANCOMYCIN
5.9%
29.7%
21.8%
15.9%
7.9%
18.8%
Underweight Normal Weight
Overweight Moderate Obesity
Severe Obesity Morbid Obesity
RESULTS
PATIENT
CHARACTERISTICS
(N=239)
Characteristic Median (IQR) or n (%)
Age (years) 61 (49-75)
Female
Male
102 (42.7%)
137 (57.3%)
Caucasian
African American
Asian
Other
225 (94.1%)
6 (2.5%)
5 (2.1%)
3 (1.2%)
Height (inches) 68 (64-71)
Total body weight (kg) 82.1 (66-107.5)
Serum creatinine 0.93 (0.70-1.22)
* World Health Organization Definitions
PHARMACOKINETIC EQUATIONS
Ke = ln (Cmin/Cmax) /Δt Vd = (Dose/t') x (1 − e−kt')/ k (Cmax − [Cmin x e−keτ']) ClVANCO = Vd x ke
Cockcroft-Gault (mL/min): eCLcr= [(140-age) x (TBW/IBW/ABW/LBW)) x 0.85 (if female)]
/(72 x SCr)
MDRD (mL/min/1.73 m2): eGFR =175 x (SCr)-1.154 x (Age)-0.203 x (0.742 if female) x (1.212 if
black)
CKD-EPI (mL/min/1.73 m2): GFR = 141 X min(SCr/κ,1)α x max(SCr/κ,1)-1.209 x 0.993Age x
1.018 [if female] x 1.159 [if black]
(Where SCr =0.7 for females, 0.9 for males, α is –0.329 for females, –0.411 for males,
min indicates the minimum of SCr/κ or 1, and max indicates the maximum of SCr/κ or 1.)
1. Pai MP, Nafziger AN, Bertino JS, Jr. Simplified Estimation of
Aminoglycoside Pharmacokinetics in Underweight and Obese
Adult Patients. Antimicrob Agents and Chemother 2011;
55:4006-4011 (3);785–790.