Heteroresistentie : occulte bedreiging voor succesvolle behandeling van resistente tuberculosis

Rifampicin-resistant (RR) tuberculosis (TB) is an especially lethal
form of TB, with less than 50% of over 0.5 million patients affected
each year reaching successful treatment outcomes. Due to difficulties
in defining the full drug resistance profile in each individual patient,
there is a tremendous risk of losing key classic- (fluoroquinolones)
and new drugs (bedaquiline (BDQ)) at a faster pace than novel drugs
can be developed. The Mycobacteriology Unit at ITM is uniquely
placed due to its key role as central microbiological laboratory for the
largest RR-TB trials conducted to date. The two STREAM and two
endTB trials, enrolling over 2000 patients, allow to robustly assess
the impact of heteroresistance on treatment outcomes. In
collaboration with the University of Antwerp, we will use innovative,
state-of-the-art methods to test the hypothesis that heteroresistance
at RR-TB treatment initiation is associated with microbiological
failure. We will be the first to apply targeted deep sequencing to
clinical samples of RR-TB clinical trial participants and to quantify
culture bias in the detection of heteroresistance. In addition, we aim
to quantify the effect of treatment interruption on acquisition of
resistance to BDQ, which poses a threat to the durability of new RRTB
regimens. The results will provide a leap forward in our
knowledge and provide evidence required for defining the most
appropriate diagnostic and management strategies for patients
afflicted by RR-TB.

Rifampicin-resistant (RR) tuberculosis (TB) is an especially lethal
form of TB, with less than 50% of over 0.5 million patients affected
each year reaching successful treatment outcomes. Due to difficulties
in defining the full drug resistance profile in each individual patient,
there is a tremendous risk of losing key classic- (fluoroquinolones)
and new drugs (bedaquiline (BDQ)) at a faster pace than novel drugs
can be developed. The Mycobacteriology Unit at ITM is uniquely
placed due to its key role as central microbiological laboratory for the
largest RR-TB trials conducted to date. The two STREAM and two
endTB trials, enrolling over 2000 patients, allow to robustly assess
the impact of heteroresistance on treatment outcomes. In
collaboration with the University of Antwerp, we will use innovative,
state-of-the-art methods to test the hypothesis that heteroresistance
at RR-TB treatment initiation is associated with microbiological
failure. We will be the first to apply targeted deep sequencing to
clinical samples of RR-TB clinical trial participants and to quantify
culture bias in the detection of heteroresistance. In addition, we aim
to quantify the effect of treatment interruption on acquisition of
resistance to BDQ, which poses a threat to the durability of new RRTB
regimens. The results will provide a leap forward in our
knowledge and provide evidence required for defining the most
appropriate diagnostic and management strategies for patients
afflicted by RR-TB.