Vancomycin therapy in secondary care; investigating factors that impact therapeutic target attainment

Rawson, Timothy M; Charani, Esmita; Moore, Luke; Herrero, Pau; Baik, Ji Soo; Philip, Akash; Gilchrist, Mark; Brannigan, Eimear; Georgiou, Pantelis; Hope, William; Holmes, Alison

doi:10.1016/j.jinf.2016.12.011

Cited by 1 publication

(2 citation statements)

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“…Since a complete set of data is only available for each patient at the onset of treatment, parameters were assumed to stay constant throughout the treatment period for analysis of the dataset [4]. Population and individual pharmacokinetic parameters we estimated with Pmetrics, an R programming language package developed by the USC Laboratory of Applied Pharmacokinetics (LAPK) (Los Angeles, CA, US) for non-parametric and parametric PK-PD modelling and simulation [15].…”

Section: Parameter Identificationmentioning

confidence: 99%

“…A growing body of evidence is emerging to suggest that we are failing to dose patients appropriately with many commonly used antimicrobial agents [3], [4]. This has led to calls for the development of individualised antimicrobial regimens that consider intra-and inter-individual variation which drives observed drug pharmacokinetic (PK) variation.…”

Section: Introductionmentioning

confidence: 99%

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Closed-Loop Control for Precision Antimicrobial Delivery: An <italic>In Silico</italic> Proof-of-Concept

Herrero

Rawson

Philip³

et al. 2018

IEEE Trans. Biomed. Eng.

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Abstract-Objective: Inappropriate dosing of patients with antibiotics is a driver of antimicrobial resistance, toxicity, and poor outcomes of therapy. In this paper, we investigate, in silico, the hypothesis that the use of a closed-loop control system could improve the attainment of pharmacokinetic-pharmacodynamic targets for antimicrobial therapy, where wide variations in target attainment have been reported. This includes patients in critical care, patients with renal disease and patients with obesity. Methods: The presented in silico study focuses on vancomycin delivery, a first line therapy for Methicillin-resistant Staphylococcus aureus (MRSA) that has serious side effects, including nephrotoxicity. For this purpose, an in silico platform for the simulation of pharmacokinetics of vancomycin agents was developed including 24 virtual non-critically ill adult subjects obtained from routinely collected data from two prospective audits of vancomycin therapy. Intra-day variability on renal clearance, sensor error and infusion constraints were taken into account. Proportional Integral Derivative (PID) controller was chosen because of its simplicity of implementation and satisfactory performance. Results: Even though significant intra-day variability and sensor error were considered in the simulations, by assuming a minimum inhibitory concentration of 1 mg/l for MRSA, the proposed controller was able to reach the well-established therapeutic target of 24-hour area under curve to minimum inhibitory concentration ratio equal to 400 mg · h/l for all the studied subjects, while staying significantly below toxic levels. Conclusion: A PID controller has the potential to precisely deliver a vancomycin therapy in a non-critically ill adult population. Significance: Closed-loop control for precision Vancomycin delivery can potentially reduce toxicity and poor therapeutic outcomes, as well as reduce antimicrobial resistance.

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Section: Parameter Identificationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%