Abstract
Therapeutic drug monitoring (TDM) is increasingly relevant for an individualized antibiotic therapy and subsequently a necessary tool to reduce multidrug-resistant pathogens, especially in light of diminishing antimicrobial capabilities. Critical illness is associated with profound pharmacokinetic and pharmacodynamic alterations, which challenge dose finding and the application of particularly hydrophilic drugs such as β-lactam antibiotics. Methods: Implementation strategy, potential benefit, and practicability of the developed standard operating procedures were retrospectively analyzed from January to December 2020. Furthermore, the efficacy of the proposed dosing target of piperacillin in critically ill patients was evaluated. Results: In total, 160 patients received piperacillin/tazobactam therapy and were subsequently included in the study. Of them, 114 patients received piperacillin/tazobactam by continuous infusion and had at least one measurement of piperacillin serum level according to the standard operating procedure. In total, 271 measurements were performed with an average level of 79.0 ± 46.0 mg/L. Seventy-one piperacillin levels exceeded 100 mg/L and six levels were lower than 22.5 mg/L. The high-level and the low-level group differed significantly in infection laboratory parameters (CRP (mg/dL) 20.18 ± 11.71 vs. 5.75 ± 5.33) and renal function [glomerular filtration rate (mL/min/1.75 m2) 40.85 ± 26.74 vs. 120.50 ± 70.48]. Conclusions: Piperacillin levels are unpredictable in critically ill patients. TDM during piperacillin/tazobactam therapy is highly recommended for all patients. Although our implementation strategy was effective, further strategies implemented into the daily clinical workflow might support the health care staff and increase the clinicians’ alertness.
Highlights
Sepsis is defined as a life-threatening organ dysfunction due to a dysregulated host response to bacteria or their components [1]
With a total of 742 patients treated from January to December 2020, 160 patients received PIP/TAZ at least once during an intensive care unit stay
The optimal diagnostic choice currently seems to be chromatography combined with mass spectrometry (LC-MS), which is mostly based on locally developed standards [16]
Summary
Sepsis is defined as a life-threatening organ dysfunction due to a dysregulated host response to bacteria or their components [1]. An estimated incidence of 48.9 million sepsis cases were recorded in 2017 worldwide, resulting in 11 million sepsis related deaths, thereby contributing to a global overall lethality of 20% [2]. Antimicrobial therapy is an essential key issue in the management of patients with bacterial infections, sepsis, and septic shock. Inappropriate empirical antimicrobial therapy results in significantly increased morbidity and mortality [3]. Every delay in the application of an adequate antimicrobial therapy causes an increased mortality [4]. Several mechanisms including the release of vasodilative mediators and cytokines as well as the activation of immune cells affect most aspects of endothelial cell function, subsequently resulting in impaired vasoregulation, barrier function, inflammation, and hemostasis [5]
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