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@article{Herrero:2022:10.3389/fbioe.2022.1015389,
author = {Herrero, Vinas P and Wilson, R and Armiger, R and Roberts, J and Holmes, A and Georgiou, P and Rawson, T},
doi = {10.3389/fbioe.2022.1015389},
journal = {Frontiers in Bioengineering and Biotechnology},
title = {Closed-loop control of continuous piperacillin delivery: an in silico study},
url = {http://dx.doi.org/10.3389/fbioe.2022.1015389},
volume = {10},
year = {2022}
}

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TY  - JOUR
AB  - 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-minute sampling period, targeting a serum piperacillin concentration between 32-64 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.
AU  - Herrero,Vinas P
AU  - Wilson,R
AU  - Armiger,R
AU  - Roberts,J
AU  - Holmes,A
AU  - Georgiou,P
AU  - Rawson,T
DO  - 10.3389/fbioe.2022.1015389
PY  - 2022///
SN  - 2296-4185
TI  - Closed-loop control of continuous piperacillin delivery: an in silico study
T2  - Frontiers in Bioengineering and Biotechnology
UR  - http://dx.doi.org/10.3389/fbioe.2022.1015389
UR  - http://hdl.handle.net/10044/1/100433
VL  - 10
ER  -

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