654.   Pharmacodynamic (PD) Profiling of Daptomycin (DAP) Against Methicillin Resistant Staphylococcus Aureus for the Treatment of Serious Infections in USA Medical Centers
Session: Poster Abstract Session: Pharmacokinetics and Adverse Drug Reactions
Friday, October 21, 2011
Room: Poster Hall B1
Handouts
  • DAP.2011.pdf (334.1 kB)
  • Background: Empiric dosing of Daptomycin (DAP) to achieve a Cumulative Fraction of Response (CFR) of > 90% based on the MIC distribution of US MRSA isolates at various levels of renal function has not been examined. Consequently, the optimal empiric dosing regimen for  DAP in serious infections remains unclear.

    Methods: Previously published pharmacokinetic data (AAC, 2004 Aug., n=282) and MIC data of 4513 MRSA isolates for DAP (IDSA 2010, Poster #246) were used in this analysis. Doses up to 12 mg/kg were evaluated for Probability of Target Attainment (PTA) with Monte Carlo Simulation (MCS, n=5000) for different levels of renal function at the MIC ranges of 0.125 to 2 mg/L. CFR was calculated for each regimen targeting an AUC/MIC necessary to achieve a killing of 2 log10  CFU. The minimum amount of drug and the respective dosing interval necessary to produce a CFR > 90% was then evaluated for safety using MCS and a two compartment model with constant intravenous input and first order output.

    Results: DAP regimens expected to achieve the CFR > 90% at the renal function of 20, 40, 60, 80, 100, 120 ml/min are 10mg/kg q48h, 5mg/kg q24h, 6mg/kg q24h, 7mg/kg q24h, 8mg/kg q24h and 9mg/kg q24h, respectively. The MCS also showed that - based on the CFRs achieved by the manufacturer recommended dose and dosing intervals -  it is likely that empiric dosing will result in sub-optimal PTAs for patients with creatinine clearance outside of the range of 31 – 60 ml/min. 

    Conclusion:We conclude that for the treatment of serious MRSA infections to achieve the killing of 2 log10  CFU, the revised dosing method would provide better empiric population PTA compared to manufacturer recommendations. 


    Subject Category: J. Clinical practice issues

    Andras Farkas, PharmD, PHARMACY, NYACK HOSPITAL, NYACK, NY and Catherine Hoffman, BS, MICROBIOLOGY, NYACK HOSPITAL, NYACK, NY

    Disclosures:

    A. Farkas, None

    C. Hoffman, None

    Findings in the abstracts are embargoed until 12:01 a.m. EST Thursday, Oct. 20 with the exception of research findings presented at IDSA press conferences.