Delivering precision antimicrobial therapy through closed-loop control systems

T M Rawson¹, D O'Hare², P Herrero³, S Sharma⁴, L S P Moore^{1

5}, E de Barra⁵, J A Roberts^{6

7}, A C Gordon⁸, W Hope⁹, P Georgiou³, A E G Cass¹⁰, A H Holmes^{1

5}

Affiliations

¹ National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.
² Department of Bioengineering, Imperial College London, London SW7 2AZ, UK.
³ Department of Electrical and Electronic Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.
⁴ College of Engineering, Swansea University, Swansea SA1 8EN, UK.
⁵ Imperial College Healthcare NHS Trust, Hammersmith Hospital, Du Cane Road, Acton W12 0NN, UK.
⁶ University of Queensland Centre for Clinical Research, Faculty of Medicine and Centre for Translational Pharmacodynamics, School of Pharmacy, The University of Queensland, Brisbane, Australia.
⁷ Royal Brisbane and Women's Hospital, Brisbane, Australia.
⁸ Section of Anaesthetics, Pain Medicine & Intensive Care, Imperial College London, London SW7 2AZ, UK.
⁹ Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool L69 3GE, UK.
¹⁰ Department of Chemistry & Institute of Biomedical Engineering, Imperial College London, Kensington Campus, London SW7 2AZ, UK.

PMID: 29211877
PMCID: PMC5890674
DOI: 10.1093/jac/dkx458

Review

Delivering precision antimicrobial therapy through closed-loop control systems

T M Rawson et al. J Antimicrob Chemother. 2018.

. 2018 Apr 1;73(4):835-843.

doi: 10.1093/jac/dkx458.

Authors

T M Rawson¹, D O'Hare², P Herrero³, S Sharma⁴, L S P Moore^{1

5}, E de Barra⁵, J A Roberts^{6

7}, A C Gordon⁸, W Hope⁹, P Georgiou³, A E G Cass¹⁰, A H Holmes^{1

5}

Affiliations

¹ National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.
² Department of Bioengineering, Imperial College London, London SW7 2AZ, UK.
³ Department of Electrical and Electronic Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.
⁴ College of Engineering, Swansea University, Swansea SA1 8EN, UK.
⁵ Imperial College Healthcare NHS Trust, Hammersmith Hospital, Du Cane Road, Acton W12 0NN, UK.
⁶ University of Queensland Centre for Clinical Research, Faculty of Medicine and Centre for Translational Pharmacodynamics, School of Pharmacy, The University of Queensland, Brisbane, Australia.
⁷ Royal Brisbane and Women's Hospital, Brisbane, Australia.
⁸ Section of Anaesthetics, Pain Medicine & Intensive Care, Imperial College London, London SW7 2AZ, UK.
⁹ Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool L69 3GE, UK.
¹⁰ Department of Chemistry & Institute of Biomedical Engineering, Imperial College London, Kensington Campus, London SW7 2AZ, UK.

PMID: 29211877
PMCID: PMC5890674
DOI: 10.1093/jac/dkx458

Abstract

Sub-optimal exposure to antimicrobial therapy is associated with poor patient outcomes and the development of antimicrobial resistance. Mechanisms for optimizing the concentration of a drug within the individual patient are under development. However, several barriers remain in realizing true individualization of therapy. These include problems with plasma drug sampling, availability of appropriate assays, and current mechanisms for dose adjustment. Biosensor technology offers a means of providing real-time monitoring of antimicrobials in a minimally invasive fashion. We report the potential for using microneedle biosensor technology as part of closed-loop control systems for the optimization of antimicrobial therapy in individual patients.

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Figures

**Figure 1.**
Schematic for closed-loop control of antimicrobial delivery.

See this image and copyright information in PMC

References

1. O’Neill J. 2016. Tackling Drug-Resistant Infections Globally: Final Report and Recommendations https://amr-review.org/sites/default/files/160518_Final%20paper_with%20c....
1. Holmes AH, Moore LSP, Sundsfjord A. et al. Understanding the mechanisms and drivers of antimicrobial resistance. Lancet 2016; 387: 176–87. - PubMed
1. Roberts JA, Abdul-Aziz MH, Lipman J. et al. Individualised antibiotic dosing for patients who are critically ill: challenges and potential solutions. Lancet Infect Dis 2014; 14: 498–509. - PMC - PubMed
1. Perez F, El Chakhtoura NG, Papp-Wallace K. et al. Treatment options for infections caused by carbapenem-resistant Enterobacteriaceae: can we apply ‘precision medicine’ to antimicrobial chemotherapy? Expert Opin Pharmacother 2016; 17: 761–81. - PMC - PubMed
1. Abdul-Aziz MH, Roberts JA, Lipman J. et al. Applying pharmacokinetic/pharmacodynamic principles in critically ill patients: optimizing efficacy and reducing resistance development. Semin Respir Crit Care Med 2015; 36: 136–53. - PubMed

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Delivering precision antimicrobial therapy through closed-loop control systems

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Delivering precision antimicrobial therapy through closed-loop control systems

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