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

 

Meropenem

Piperacillin

Tazobactam

Midpoint

Trough

Midpoint

Trough

Midpoint

Trough

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

3.86

1.36

14.51

5.68

1.97

1.04

High Value

41.45

26.38

311.26

269.78

42.61

36.77

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

Disclosures:

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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