Closed-loop control of continuous piperacillin delivery: An in silico study

Herrero, Pau, Wilson, Richard C ORCID: 0000-0002-3275-6932, Armiger, Ryan, Roberts, Jason A, Holmes, Alison ORCID: 0000-0001-5554-5743, Georgiou, Pantelis and Rawson, Timothy M ORCID: 0000-0002-2630-9722 (2022) Closed-loop control of continuous piperacillin delivery: An in silico study. FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY, 10. 1015389-.

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Official URL: http://dx.doi.org/10.3389/fbioe.2022.1015389

Abstract

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.

Item Type:	Article
Uncontrolled Keywords:	antimicrobials, beta-lactam, pharmacokinetics-pharmacodynamics, therapeutic drug monitoring, critical illness, closed-loop control
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	28 Mar 2023 09:22
Last Modified:	18 Oct 2023 11:33
DOI:	10.3389/fbioe.2022.1015389
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3169287