期刊
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
卷 10, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fbioe.2022.1015389
关键词
antimicrobials; beta-lactam; pharmacokinetics-pharmacodynamics; therapeutic drug monitoring; critical illness; closed-loop control
资金
- Department of Health and Social Care (DHSC)
- [APP2007007]
- [APP2009736]
This paper investigates whether closed-loop control can improve pharmacokinetic-pharmacodynamic target attainment of piperacillin-tazobactam in critically-ill patients. The study finds that a PID controller driven by ISF drug concentration measurements significantly improves target attainment compared to traditional infusion methods.
Background and objective: Sub-therapeutic dosing of piperacillin-tazobactam in critically-ill patients is associated with poor clinical outcomes and may promote the emergence of drug-resistant infections. In this paper, an in silico investigation of whether closed-loop control can improve pharmacokinetic-pharmacodynamic (PK-PD) target attainment is described. Method: An in silico platform was developed using PK data from 20 critically-ill patients receiving piperacillin-tazobactam where serum and tissue interstitial fluid (ISF) PK were defined. Intra-day variability on renal clearance, ISF sensor error, and infusion constraints were taken into account. Proportional-integral-derivative (PID) control was selected for drug delivery modulation. Dose adjustment was made based on ISF sensor data with a 30-min sampling period, targeting a serum piperacillin concentration between 32 and 64 mg/L. A single tuning parameter set was employed across the virtual population. The PID controller was compared to standard therapy, including bolus and continuous infusion of piperacillin-tazobactam. Results: Despite significant inter-subject and simulated intra-day PK variability and sensor error, PID demonstrated a significant improvement in target attainment compared to traditional bolus and continuous infusion approaches. Conclusion: A PID controller driven by ISF drug concentration measurements has the potential to precisely deliver piperacillin-tazobactam in critically-ill patients undergoing treatment for sepsis.
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