957. Pharmacodynamic Target Attainment for Meropenem and Piperacillin/Tazobactam Using a PK/PD-based Dosing Calculator in Critically Ill Patients
Session: Oral Abstract Session: Stewardship Tools
Friday, October 6, 2017: 8:45 AM
Room: 05AB

Background: Unbound plasma concentrations of beta-lactam antibiotics vary widely and attainment of PK/PD targets is highly variable in critically ill patients, which may affect microbiologic cure or contribute to toxicity.  PK/PD-based antibiotic dosing programs may provide more accurate doses that achieve predicted targets for a cultured organism.

Methods: This was a single center, prospective study of critically ill patients with culture positive gram-negative infections treated with meropenem (MEM) or piperacillin/tazobactam (TZP). A PK/PD-based antibiotic dosing app was used to select doses that had a probability of target attainment (PTA) of 90% or greater for time above MIC (fT>MIC) of at least 40% for MEM and 50% for TZP.  Total meropenem, piperacillin and tazobactam mid-point and trough concentrations were obtained at steady state and adjusted for protein binding, to assess target attainment.

Results: 36 patients were enrolled; 20 received MEM and 16 TZP. Antibiotic concentrations varied widely amongst patients, particularly with TZP.  MEM and TZP concentrations are displayed in Table 1 and Figure 1.  Doses evaluated for >90% probability of target attainment in the dosing calculator differed from standard package labeled doses for 25% (5/20) of MEM and 18.8% (3/16) of TZP patients.  All (20/20) MEM and 94% (15/16) TZP patients maintained fT>MIC for the entire dosing interval.  

Conclusion:  A PK/PD based antibiotic dosing calculator that provides individualized beta-lactam doses can lead to altered doses that may increase probability of target attainment in critically ill patients.  Future research is needed to review the relevance of PK/PD-based dose adjustments on clinical outcomes.

Table 1: Meropenem, Piperacillin and Tazobactam Concentrations Adjusted for Protein Binding in mcg/mL











Mean (SD)

15.93 (11.23)

9.24 (8.34)

81.25 (81.79)

46.65 (62.69)

16.09 (12.00)

10.70 (12.45)

Low Value







High Value







Median Organism MIC (range)

0.25 (0.25-4)

6 (4-32)


Emily Heil, PharmD, BCPS-AQID, Pharmacy Practice and Science, University of Maryland School of Pharmacy, Baltimore, MD, David P. Nicolau, PharmD, FCCP, FIDSA, Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT, Gwen Robinson, MPH, University of Maryland School of Medicine, Baltimore, MD, Andras Farkas, PharmD, Mount Sinai West Hospital, New York, NY; Computer Simulation Studies, Optimum Dosing Strategies, BLOOMINGDALE, NJ and Kerri Thom, MD, MS, University of Maryland, Baltimore, Baltimore, MD


E. Heil, None

D. P. Nicolau, Shionogi & Co.: Research Contractor , Research support

G. Robinson, None

A. Farkas, Optimum Dosing Strategies: Employee , Salary

K. Thom, None

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