Pharmacodynamic Target Attainment for Meropenem and Piperacillin/Tazobactam Using a PK/PD-based Dosing Calculator in Critically Ill Patients

BACKGROUND: Unbound plasma concentrations of β-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: Thirty-six 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 β-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. DISCLOSURES: D. P. Nicolau, Shionogi & Co.: Research Contractor, Research support; A. Farkas, Optimum Dosing Strategies: Employee, Salary.