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Optimizing Levofloxacin Dose in the Treatment of Multidrug-Resistant Tuberculosis An Integrated PK/PD Approach

PhD ceremony:S. Ghimire
When:April 10, 2019
Start:16:15
Supervisors:dr. J.W.C. (Jan-Willem) Alffenaar, prof. dr. D.J. (Daan) Touw, prof. dr. T.S. (Tjip) van der Werf
Where:Academy building RUG
Faculty:Medical Sciences / UMCG

Tuberculosis (TB) is an infectious disease that is transmitted through air from infected person  through coughing, sneezing or talking. The tubercle bacillus or Mycobacterium tuberculosis is the causative organism of tuberculosis. When tubercle bacillus is resistant to two most important first line drugs: isoniazid and rifampicin, patients develop multi-drug resistant tuberculosis (MDR-TB). The treatment duration for MDR-TB lasts long, for at least 9-12 months and up to  two years. Moreover, second-line medicines must be used that have far more side effects  and are less effective. The treatment success results are unfavorable worldwide, which fails in nearly half of the treated MDR-TB patients. How can we improve the treatment results? This dissertation tries to contribute to the knowledge on one of the most important medicines for MDR-TB in order to ultimately improve the treatment results. Based on the results from levofloxacin levels in blood, we have shown that currently used levofloxacin dose in MDR-TB patients is insufficient. The medicine levels that are too low in combination with reduced bacterial sensitivity lead to an increased chance of therapy failure. Therapeutic drug monitoring enables clinicians to adjust dosage of medicines based on levels achieved in blood. Different patients on same dosages achieve a range of concentrations due to inter-individual variability. Therefore, knowledge about individual medicine levels, bacterial susceptibility and disease severity in the patient can help in adjusting drug dosages in individual patients. It’s time for precision medicine in the treatment of tuberculosis.