Therapeutic drug monitoring-based dose optimisation of piperacillin and meropenem: A randomised controlled trial

Purpose: There is variability in the pharmacokinetics (PK) of antibiotics (AB) in critically ill patients. Therapeutic drug monitoring (TDM) could overcome this variability and increase PK target attainment. The objective of this study was to analyse the effect of a dose-adaption strategy based on daily TDM on target attainment. Methods: This was a prospective, partially blinded, and randomised controlled trial in patients with normal kidney function treated with meropenem (MEM) or piperacillin/tazobactam (PTZ). The intervention group underwent daily TDM, with dose adjustment when necessary. The predefined PK/pharmacodynamic (PK/PD) target was 100 % fT_>4MIC [percentage of time during a dosing interval that the free (f) drug concentration exceeded 4 times the MIC]. The control group received conventional treatment. The primary endpoint was the proportion of patients that reached 100 % fT_>4MIC and 100 % fT_>MIC at 72 h. Results: Forty-one patients (median age 56 years) were included in the study. Pneumonia was the primary infectious diagnosis. At baseline, 100 % fT_>4MIC was achieved in 21 % of the PTZ patients and in none of the MEM patients; 100 % fT_>MIC was achieved in 71 % of the PTZ patients and 46 % of the MEM patients. Of the patients in the intervention group, 76 % needed dose adaptation, and five required an additional increase. At 72 h, target attainment rates for 100 % fT_>4MIC and 100 % fT_>MIC were higher in the intervention group: 58 vs. 16 %, p = 0.007 and 95 vs. 68 %, p = 0.045, respectively. Conclusions: Among critically ill patients with normal kidney function, a strategy of dose adaptation based on daily TDM led to an increase in PK/PD target attainment compared to conventional dosing.