Is therapeutic drug monitoring really helpful for managing piperacillin/tazobactam therapy in critically ill patients?

Excerpt

We read with interest the study from Hagel et al. that found no beneficial effect of therapeutic drug monitoring (TDM)-based dose optimization of piperacillin/tazobactam (PIP/TAZ) on sepsis-related organ dysfunction in patients with sepsis [1]. No differences were observed between the TDM and the control groups in 28-day survival, occurrence of PIP toxicity, or clinical or microbiological cure rates. Interestingly, no differences were observed in the mean PIP/TAZ total daily dose or in the median PIP concentrations. Only a significantly higher 28-day mortality rate was observed after adjustment for disease severity based on baseline sequential organ failure assessment (SOFA) score in patients with PIP levels above 96 mg/L on day 1 after randomization. These patients presented also the lowest renal clearance rate (2.2 mL/min). In addition, significantly better resolution of organ dysfunction was shown after adjustment of the Acute Physiology and Chronic Health Evaluation (APACHE) II score in patients with better PIP exposure in the first two days. As previously described, these points highlight the importance of PIP exposure in the early phase of sepsis [2] and the significant influence of renal function on PIP concentration [3]. Thus, we believe that Hagel et al. should have discussed two potential biases: (1) the use of similar initial treatment regimens in the two study groups and (2) the interdependence between estimated glomerular filtration rate (eGFR) and PIP concentration and its consequence on PIP dose adjustment based on renal function or TDM. …