796. Optimizing Beta-Lactam Pharmacodynamics Against Pseudomonas aeruginosa in Adult Cystic Fibrosis Patients
Session: Poster Abstract Session: Antimicrobial Agents: PK/PD Studies
Friday, October 9, 2015
Room: Poster Hall
Posters
  • ID Week Poster ThompsonRZ (Final Draft).pdf (828.0 kB)
  • Background:

    Beta-lactam antibiotics with activity against Pseudomonas aeruginosa (PSA) are commonly used in the treatment of cystic fibrosis (CF) pulmonary exacerbations.  Patients with CF exhibit increased total body clearance of beta-lactams leading to the potential inability to reach the desired pharmacodynamic target against PSA.  The purpose of this study was to predict the likelihood of beta-lactams reaching their pharmacodynamic target in adult CF patients based on local MIC data.

    Methods:

    Pharmacokinetic parameters and variability as well as protein binding were obtained from the CF literature for aztreonam (ATM), cefepime (FEP), ceftazidime (CAZ), meropenem (MEM) and piperacillin-tazobactam (TZP). MICs were determined by E-test® for all non-duplicate isolates obtained in 2013.  Monte Carlo simulations were performed to determine the likelihood of pharmacodynamic target attainment for bolus, three-hour, and continuous infusion regimens of 2 g q8h for ATM, FEP, CAZ, MEM and 4.5 g q6h for TZP.  The targeted %fT>MIC was 40% for carbapenems, 50% for penicillins and 60% for cephalosporins and monobactams. 

    Results:

    Overall, 43 isolates of PSA were included for analysis.  The MIC50, MIC90 and percent susceptible were 8, 512, and 56% for ATM; 16, 512, and 49% for FEP; 4, 512, and 70% for CAZ; 1, 64, and 65% for MEM; 8, 512, and 61% for TZP, respectively. Table 1 provides the probability of target attainment for each of the simulated regimens. No regimen reached a probability of target attainment of >90% against PSA in CF patients at our institution.  However, prolonged and continuous infusion provided significantly higher probability of target attainment than intermittent bolus for all antibiotic regimens.

    Table 1. Probability of Target Attainment for Antibiotic Regimens                

     

    Probability of Target Attainment (%)

    Antibiotic Regimen

    Bolus

    Regimen

    Three-hour

    Prolonged Infusion

    Continuous Infusion

    ATM 2g q8h

    46

    58

    62

    FEP 2g q8h

    32

    62

    66

    CAZ 2g q8h

    56

    73

    75

    MEM 2g q8h

    70

    83

    78

    TZP 4.5g q6h

    57

    72

    72

    Conclusion:

    Standard beta-lactam regimens inadequately obtain the desired pharmacodynamic target against PSA in CF patients. Further investigation of novel antimicrobial dosing regimens including combination therapy is needed.

    Robert Z. Thompson, PharmD1,2, Craig Martin, PharmD1,2, Donna R. Burgess, RPh1, W. Cliff Rutter, PharmD2 and David S. Burgess, PharmD, FCCP2, (1)University of Kentucky HealthCare, Lexington, KY, (2)University of Kentucky, College of Pharmacy, Lexington, KY

    Disclosures:

    R. Z. Thompson, None

    C. Martin, None

    D. R. Burgess, None

    W. C. Rutter, None

    D. S. Burgess, None

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