641. Antimicrobial Therapy Optimization by Institute-specific Pharmacodynamics Profiling
Session: Poster Abstract Session: Pharmacokinetics and Adverse Drug Reactions
Friday, October 21, 2011
Room: Poster Hall B1
  • IDSA Poster - 4x6 - Antimicrobial Therapy Optimization by Institute-specific Pharmacodynamics Profiling - Final Version - Online View.pdf (371.2 kB)
  • Background: 

    Pharmacodynamic dose optimizing of beta-lactam agents utilizing extended infusion (EI) of  piperacillin/tazobactam (P-T) and doripenem have been implemented in the Intensive Care Units (ICU) at Summa Health System since September 2007. Published data has demonstrated that EI improves patients’ survival and clinical outcome. Extended infusion protocol included P-T 3.375g q8H over 4 hours and doripenem 500 mg q8H over 4 hours for empiric treatment. Previously published data has suggested the P-T 3.375 g q8h over 4 hours regimen may be inadequate for Pseudomonas with higher minimal inhibitory concentrations (MICs) within the susceptibility range. We sought to investigate and define the antimicrobial therapy dose optimization of various anti-pseudomonal agents for our institution.


    Fifty-one non-duplicate non-urinary Pseudomonas and twenty Acinetobacter isolates were collected between January and April 2010. MICs were performed using published CLSI guidelines and pharmacokinetic modeling utilizing Monte Carlo simulation was performed in conjunction with the Center for Anti-Infective Research at Hartford Hospital. Cumulative fraction response (CFR) of different dosing regimens were obtained for anti-pseudomonal antimicrobials based on the MIC information regarding the Pseudomonas and Acinetobacter isolates.


    For Pseudomonas, P-T 3.375g q8H over 4 hours achieved CFR of 79% while P-T 4.5 g q6h over 3 hours achieved CFR of 85%. Doripenem 500mg q8H achieved 75% CFR, whereas increasing Doripenem dose to 1 g q8H over 4 hours increased CFR to 97%. For cefepime, a dosing regimen of 2 g q8H over 3 hours achieved the highest CFR at 89%.  In regards to Acinetobacter most anti-pseudomonal agents exhibited poor CFR. Doripenem 1 g q8H over 4 hours achieved the highest CFR at 25%.


    Pharmacodynamic profiling of antibiotic agents to enhance the likelihood of microbiological success against Pseudomonas led to changes in the extended infusion protocols. The doses of P-T and doripenem were increased to optimize dosing as well as the addition of EI Cefepime to the protocol. Each institution is encouraged to investigate and analyze their own gram-negative isolates to determine optimal dosing.

    Subject Category: A. Antimicrobial agents and Resistance

    Anthony Leung, DO, FACP, FASCP1, David Nicolau, PharmD, FCCP, FIDSA2, Joseph DiPersio, PhD1 and Timothy R. Pasquale, PharmD1, (1)Summa Health System, Akron, OH, (2)Center for Anti-Infective Research and Development, Hartford, CT


    A. Leung, None

    D. Nicolau, Rib-X Pharmaceuticals: Consultant and Grant Investigator, Consulting fee and Grant recipient

    J. DiPersio, None

    T. R. Pasquale, 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.