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Optimising the use of oral antimicrobial agents through pharmacokinetic and pharmacodynamic (PK-PD) analysis, application of novel biosensor technology, and enhanced therapeutic drug monitoring.


   Department of Infectious Disease

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  Dr Tim Rawson, Prof A Holmes, Dr D O'Hare, Dr Matt Ellington  No more applications being accepted  Competition Funded PhD Project (European/UK Students Only)

London United Kingdom Pharmaceutical Chemistry Pharmacology

About the Project

Background

This is an exciting opportunity to be one of a four student cohort, working at the NIHR Health Protection Research Unit in Healthcare Associated Infection (HCAI) and Antimicrobial Resistance (AMR) at Imperial College London.

The Unit is a collaboration between Imperial College London and its partners, Public Health England, Imperial College Health Partners, Warwick University, and Cambridge Veterinary School.  

The ethos of the Unit is one which embraces interdisciplinarity and multi-professional research to tackle AMR and HCAI, producing a vibrant and diverse research environment in which world-class facilities and access to international experts make the exploration of exciting and innovative research projects across the breadth of AMR possible. 

The Unit’s Director, Professor Alison Holmes and our Theme Leads represent international expertise from the Faculty of Medicine, the Faculty of Engineering, the Dyson School of Design, the School of Public Health and the Centre for Molecular Bacteriology and Infection.

Depending on the choice of project, there are also opportunities to collaborate with two other HPRUs at Imperial; the HPRU in Respiratory Infection and the HPRU in Modelling Methodologies and Health Economics. Whichever project you choose, you will be working closely with our experienced research staff who include bench scientists, medics, epidemiologists, pharmacists and systems dynamics modellers. You will also be supported by the Unit’s dedicated administrative team who can assist students in adopting patient and public engagement in their projects and in applying for post-doctoral fellowships at the end of their studies.

The Project

This is a 3 year PhD studentship with a stipend of £18,000 per annum. Fees are available at the home rate only.

Improving the precision use of current antimicrobials is of critical importance. This can include the better selection (when to start, choice, and combination), dosing, and determination of an appropriate duration of antimicrobial therapy. Improving the precision with which antimicrobials are used can lead to better clinical outcomes from infection, reduce the risk of toxicity, and reduce the emergence of drug-resistance. In-vitro data demonstrate that antimicrobial dose optimisation is a critical mechanism through which the development of drug-resistance, and thus antimicrobial resistance (AMR) may be slowed. This may be achieved by delivering optimal doses of drug to suppress resistant subpopulations, understanding drug exposures that prevent the emergence of AMR, and explore optimal durations of treatment. In addition to direct patient impact, suboptimal antimicrobial therapy can have important economic consequences. A focus on optimisation of antimicrobial dosing as part of precision prescribing may support the use of less expensive agents, shorter durations of therapy, and reductions in the rate of development of AMR.

The PhD candidate will explore oral antimicrobial pharmacokinetics and pharmacodynamics (PK-PD). They will identify target antimicrobials and infections of clinical importance. They will work with clinical trials, chemistry, bioengineering, and electrical engineering to develop novel solutions to support the optimsation of oral antimicrobial therapy for these important clinical areas.

Eligibility Criteria

To apply you must have a minimum of an upper second class honours degree or equivalent, meet the College’s English language requirement and meet the criteria to be eligible for home fees.

 To apply for this position please, use the enquiry form below to send a cover letter explaining why you are a suitable candidate for this PhD studentship, together with your CV and the names of two referees.


Funding Notes

The intended start date is prior to the 31 July 2021. As such Home fee classification and studentship awards will be determined according the existing fee regulations. However, EEA/Swiss nationals should be aware that if for any reason they do not commence studies by the 31st July, they will be subject to re-assessment against the new (amended) fee regulations and depending on their circumstance, they may loose an entitlement to Home fee status or the studentship. Under such circumstances, affected students would need to withdraw, or self-fund their studies at the overseas fee rates

References

Rawson TM, Gowers SAN, Freeman DME Freeman, Wilson RC, Sharma S, Gilchrist M, MacGowan A, Lovering A, Bayliss M, Kyriakides M, Georgiou P, Cass AE, O’Hare D, Holmes A. Microneedle biosensors for real-time drug monitoring of phenoxymethylpenicillin: a first-in-human evaluation in healthy volunteers. The Lancet Digital Health. 2019 [Epub ahead of print] https://doi.org/10.1016/S2589-7500(19)30131-1
Gowers SAN, Freeman DME, Rawson TM, Rogers ML, Wilson RC, Holmes AH, Cass AE, O'Hare D. Development of a Minimally Invasive Microneedle-Based Sensor for Continuous Monitoring of β-Lactam Antibiotic Concentrations in Vivo. ACS Sens. 2019 Apr 26;4(4):1072-1080. doi: 10.1021/acssensors.9b00288. Epub 2019 Apr 17. PMID: 30950598
Rawson TM, Charani E, Moore LSP, Gilchrist M, Georgiou P, Hope WW, Holmes A. Exploring C-Reactive Protein to estimate the pharmacodynamics of vancomycin. Therapeutic Drug Monitoring 2018
Rawson TM, O’Hare D, Herrero P, Sharma S, Moore L, de Barra E, Roberts J, Gordon A, Hope W, Georgiou P, Cass T, Holmes A. Delivering precision antimicrobial therapy through closed loop control. Journal of Antimicrobial Chemotherapy. 2017
Rawson TM, Sharma S, Georgiou P, Holmes A, Cass A, O'Hare D. Towards a minimally invasive device for beta-lactam monitoring in humans, Electrochemistry Communications, Vol: 82, 2017 Pages: 1-5, ISSN: 1388-2481
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