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Pharmacological approaches to optimize TB treatment

An individualized approach
PhD ceremony:Ms M.A. (Marlanka) Zuur
When:November 19, 2018
Start:14:30
Supervisors:dr. J.W.C. (Jan-Willem) Alffenaar, prof. dr. T.S. (Tjip) van der Werf, prof. dr. D.J. (Daan) Touw
Where:Academy building RUG
Faculty:Medical Sciences / UMCG

Pharmacological approaches to optimize TB treatment

In order to improve tuberculosis treatment, an individualized approach is necessary. We plead for individualized dosing based on drug exposure measured in blood – Therapeutic Drug Monitoring (TDM).To measure exposure reliably, multiple blood samples are needed, which is burdening and inconvenient for the patients. Dried blood spot sampling (DBS), a method that uses blood from a finger prick– the technique diabetes patients use to control their blood sugar levels – is a more patient-friendly approach than multiple venous blood drawings, provided that the number of samplings is not excessive. To minimize the number of blood samples, we established a limited sampling strategy for ertapenem. Ertapenem is a carbapenem antibiotic that has not (yet) been accepted for tuberculosis treatment; we discuss the potential use of ertapenem for tuberculosis treatment. We also studied fixed-dose combinations in combination with TDM. Individualization and fixed-dose may seem contradictive but we argue that TDM might detect and correct treatment mistakes resulting from fixed dosing. Susceptibility of Mycobacterium tuberculosis has traditionally been reported as either susceptible or resistant. In this thesis we propose adding a shade of grey; intermediate susceptibility that would represent a dose-dependent susceptibility category. We studied whether patients with M. tuberculosis isolates with intermediate susceptibility could be treated with a higher dose of anti-tuberculosis drugs and if so, if this approach would be cost-effective. We conclude that TDM is useful and feasible, but more research is needed to address as yet unanswered questions.