Clinical pharmacology of ertapenem in the treatment of multidrug-resistant tuberculosis

Sander Pascal van Rijn

    Research output: ThesisThesis fully internal (DIV)

    182 Downloads (Pure)

    Abstract

    Tuberculosis (TB) is caused by Mycobacterium tuberculosis and is the deadliest infectious disease worldwide. It is necessary to improve current treatment by developing more active - sterilizing - TB drugs. A particularly effective strategy is the rediscovery of old medicines as new agents for the treatment of multidrug-resistant tuberculosis (MDR-TB). Ertapenem, a beta-lactam antimicrobial drug, appears to be active against MDR-TB. To better understand the potential role of ertapenem in the treatment of M / XDR-TB, the aim of this thesis was to evaluate current literature, in vitro activity, pharmacokinetics and safety in TB patients. We investigated the potential of carbapenems for the treatment of M / XDR-TB tested. The aim of this literature review was to evaluate the currently available in vitro, in vivo and clinical data on carbapenems in the treatment of M. tuberculosis and the detection of knowledge gaps, to focus on future research. Subsequently, we developed an LC-MS / MS method, a retrospective study for all suspected MDR-TB patients who received ertapenem as part of their treatment regimen. We demonstrated the rapid decline of ertapenem during a drug susceptibility test (DST) and identified ertapenem exposure associated with optimal sterilization effect to subsequently design a once-daily dose for clinical use. Finally, we developed a Limited Sampling strategy using a population pharmacokinetic model to predict ertapenem exposure in MDR-TB patients. We conclude that 2 g ertapenem in combination with clavulanic acid can be a valuable asset in the treatment of multiresistant TB.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    Supervisors/Advisors
    • Alffenaar, Jan Willem, Supervisor
    • van der Werf, Tjip, Supervisor
    • Kosterink, Jos, Supervisor
    Award date10-Apr-2019
    Place of Publication[Groningen]
    Publisher
    Print ISBNs978-94-6332-473-1
    Publication statusPublished - 2019

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