Exploring strategies to individualize treatment with aminoglycosides and co-trimoxazole for MDR Tuberculosis

Jacob Albert Dijkstra

    Research output: ThesisThesis fully internal (DIV)

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    Abstract

    Tuberculosis (TB) is an ancient disease, still responsible for over 1 million deaths worldwide each year. TB is caused by the bacterium Mycobacterium tuberculosis, which usually infects the lungs, called pulmonary tuberculosis. Tuberculosis can also infect other parts of the body inflicting illness and several symptoms such as night sweats and weight loss, ultimately leading to death when not properly treated.

    Due to the nature and characteristics of Mycobacterium tuberculosis, antibiotic treatment is intense and takes six months with four different antibiotics to complete. Unfortunately, resistance to these so called first line drugs is increasing. Multidrug resistant tuberculosis (MDR-TB) treatment can take up to two years with second line drugs.

    One group of these second line drugs are aminoglycosides, known for their serious side effects such as irreversible hearing loss and renal toxicity. We tried to reduce the occurrence of these side effects by developing a method to individualize the dose of aminoglycosides (personalized medicine). With this method, each patient receives a tailor-made dose, reducing the occurrence of side effects. The dose reduction of the aminoglycosides did not impair the efficacy of the treatment. However, these results need to be confirmed in a randomized controlled trial before implementation in international guidelines.

    The increasing resistance of M. tuberculosis to antibiotics urges the need for new antibiotics. Co-trimoxazole, an old and cheap antimicrobial agent, has shown to be efficacious in killing M. tuberculosis. We explored the use of co-trimoxazole for the treatment of TB and performed a dose-finding study to find the right dose of co-trimoxazole. We provide essential data to perform further dose finding studies and larger scale clinical trials to implement co-trimoxazole in MDR-TB treatment.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    Supervisors/Advisors
    • van der Werf, Tjip, Supervisor
    • Kosterink, Jos, Supervisor
    • Alffenaar, Jan Willem, Co-supervisor
    • Burger, D. M., Assessment committee, External person
    • Friedrich, Alex, Assessment committee
    • Grobusch, Martin P., Assessment committee, External person
    Award date18-Oct-2017
    Place of Publication[Groningen]
    Publisher
    Print ISBNs978-94-034-0040-2
    Electronic ISBNs978-94-034-0039-6
    Publication statusPublished - 2017

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