1984. Contemporary Vancomycin Dosing in Chronic Hemodialysis (HD) Patients Does Not Meet AUC Targets: Development of a New Dosing Model Using Monte Carlo Simulation (MCS)
Session: Poster Abstract Session: Antimicrobial Pharmacokinetics and Pharmacodynamics
Saturday, October 29, 2016
Room: Poster Hall
Posters
  • Lewis_ID week 2016_Vancomycin Dosing Recommendation in HD.pdf (240.2 kB)
  • Background: Vancomycin consensus guidelines recommend achieving trough levels of 15-20mg/L to practically attain AUC/MICs >400, values linked to beneficial outcomes. However, discordance between troughs & clinical outcomes has led the new guideline writers to consider a direct AUC-based dosing approach. No studies using AUC-based dosing have been conducted in HD patients, nor have published HD dosing recommendations been assessed to determine attained AUCs. We evaluated the AUCs reached with a published HD vancomycin dosing method and devised a new regimen using MCS that would yield AUC/MICs of 400-700 in most HD patients.

    Methods: Pharmacokinetic (PK) models were developed from published demographic, PK, & dialytic information from HD patients. MCS was performed and AUC24h were calculated for the Zelenitski (CID 2012) weight-based intradialytic vancomycin regimen in 5,000 modelled patients getting 3 times a week HD (MWF) with high-flux dialyzers. Many intradialytic & postdialytic (using high & low-flux dialyzers) dosing regimens were also simulated to determine the loading (LD) & maintenance doses (MD) achieving AUC24hof 400-700 mg*h/L for MIC of 1 mg/L. A nomogram using therapeutic drug monitoring (TDM) prior to the second MD was developed.

    Results:

    Table 1. Mean AUC24hduring a Week of Zelenitsky’s Vancomycin Dosing for HD

    Vancomycin Dosing

    Mean AUC24h (mg*h/L)

    Day 1

    (Mon)

    Day 2

    (Tue)

    Day 3

    (Wed)

    Day 4

    (Thu)

    Day 5

    (Fri)

    Day 6

    (Sat)

    Day 7

    (Sun)

    1-1.5g LD, 0.5-1g MD

    291.5

    272.6

    403.3

    336.5

    376.6

    347.3

    302.6

    *Dosing on Monday, Wednesday, & Friday.

    Table 2. MCS-Derived Vancomycin HD Dosing Achieving Mean AUC24h500-700 mg*h/L

     

    Dialyzers

    LD (mg/kg)

    *MD (mg/kg)

    TDM

    Intradialytic dosing

    High flux

    35

    15

    Draw pre-HD level prior to the second MD & adjust the dose using the following equation:

     New MD (mg/kg)= [Previous MD x 20] / Pre-HD Vancomycin conc.

    Low flux

    30

    7.5

    Postdialytic dosing

    High flux

    25

    10

    Low flux

    25

    7.5

    *Any MD falling on Friday is multiplied by 130% to account for 3-day interdialytic period.

    Conclusion: Zelenitsky’s regimen is unlikely to attain desirable AUC targets. MCS suggests that more aggressive dosing using TDM is more likely to achieve AUC24h of 500-700 mg*h/L for the majority of chronic HD patients. These results warrant clinical validation.

    Susan J. Lewis, PharmD, College of Pharmacy, University of Findlay, Findlay, OH and Bruce Mueller, PharmD, College of Pharmacy, University of Michigan, Ann Arbor, MI

    Disclosures:

    S. J. Lewis, None

    B. Mueller, None

    Findings in the abstracts are embargoed until 12:01 a.m. CDT, Wednesday Oct. 26th with the exception of research findings presented at the IDWeek press conferences.