642. Variability in Relationships between Creatinine Clearance and Vancomycin Clearance: Impact on Assessment of Efficacy and Toxicity in Monte Carlo Analysis
Session: Poster Abstract Session: Pharmacokinetics and Adverse Drug Reactions
Friday, October 21, 2011
Room: Poster Hall B1
Background: Although many variables that impact Monte Carlo analysis (MCA) have been evaluated, the impact of variability in creatinine clearance (CrCl) and vancomycin (V) clearance (Cl) relationships on estimates of efficacy and nephrotoxicity (NT) has not been well studied.

Methods: From the literature, 41 CrCl vs.V Cl regressions were evaluated. 28 were eliminated based on the assay, CrCl range, number of subjects, or calculations. Of the 13 remaining, 3 populations were represented (# of studies, patients): burn patients (3, 118), critically ill (6, 170), and non-critically ill (4, 359).  MCA (1-compartment, steady-state) was performed:[1-2 g V and these intervals (hrs): CrCl>60 ml/min, 12; 31-60, 24; 15-30, 48; and <15, 72], body weights of 70-90 kg, volumes (Vd) of 0.7-0.9 L/kg, CrCl distribution (range 10-120 ml/min) and MRSA MICs (50% 1 and  50% 2 mg/L) from our institution. MCA was performed using each V Cl vs CrCl regression to assess target attainment (TA) for efficacy (AUC/MIC ≥400) and potential NT (using previous non-ICU/ ICU relationships, Lodise) and troughs ≥ 20 mg/L. ANOVA and Chi Square were used to assess slopes/intercepts, and population proportions, respectively.

Results: Wide ranges in slopes (0.342 – 0.842) and intercepts (0-57.8 ml/min) within and among the populations were found (p=NS among populations for slopes/intercepts). Results are displayed below (70 kg patient, Vd = 0.7 L/Kg):

Patients

Efficacy TA (%) 1 g

Efficacy TA (%) 2 g

NT (%) 1 g

NT (%) 2 g

Troughs ≥ 20 (%) 1 g

Troughs ≥ 20 (%) 2 g

Burns

6 - 24

49 - 74

12 - 17

24  - 40

0

6 - 41

Crit. Ill

20 - 49

67 - 99

15 - 28

34 - 72

0 - 13

36 - 94

Non-crit.

15 - 51

58 - 98

4 - 15

10 - 19

0 - 29

25 - 97

Burn patients had lower (p<0.05) TA, % NT (compared to other groups using same non-ICU/ICU data), and % troughs ≥ 20 mg/L. Larger body weights and/or Vd increased % NT by increasing troughs (max. increase 6% at 90 kg and Vd = 0.9 L/Kg).

Conclusion: The specific V Cl vs CrCl relationship used in MCA has a huge impact on TA for efficacy and potential nephrotoxicity. Thus, efficacy and toxicity may be misestimated in a specific patient population. If institution-specific Cl vs CrCl relationships are not available, care should be taken when selecting one from published literature for assessment of vancomycin efficacy and toxicity. 



Subject Category: A. Antimicrobial agents and Resistance

Roger White, PharmD and Margarita Taburyanskaya, PharmD, Medical University of South Carolina, Charleston, SC

Disclosures:

R. White, None

M. Taburyanskaya, None

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