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Optimised administration of anti-infective drugs for prophylaxis and treatment in immunocompromised patients

PhD ceremony:A. (Anne-Grete) Märtson
When:September 15, 2021
Start:09:00
Supervisors:dr. J.W.C. (Jan-Willem) Alffenaar, prof. dr. T.S. (Tjip) van der Werf
Co-supervisor:dr. M.G.G. Sturkenboom
Where:Academy building RUG
Faculty:Medical Sciences / UMCG
Optimised administration of anti-infective drugs for prophylaxis
and treatment in immunocompromised patients

One of the major global threats is antimicrobial resistance. To prevent the development of antimicrobial resistance it is important to use anti-infectives at the right dose, at the right time and for the right duration. Every anti-infective can cause certain toxicity that can occur when the drug exposure is too high or resistance can develop when exposure is too low, both of which can affect the treatment outcome.

The goal of this thesis was to investigate optimisation of anti-infective therapy in immunocompromised patients, such as transplant recipients, patients with hematological malignancies and critically ill patients. To achieve this, we explored the opportunities to improve the design of future studies; we conducted studies on therapeutic drug monitoring (TDM, measurement of drug concentrations and adjusting the dose accordingly); and we utilised data from previous clinical studies to develop population mathematic (pharmacokinetic) models to better guide drug dosing to improve drug exposure, thereby aiming to improve treatment outcome. We showed underexposure of anti-infectives in certain patient groups and designed dosing regimens that could be utilised in the clinic and further studies.

Clearly, we have only just started the journey to optimise anti-infective therapy in immunocompromised patients. To further optimise outcomes, the future challenge will be to move on to patient-level personalisation using specific targets for individuals and potentially exploring drug exposure at the site of the infection.