Frank van Leth

Associate Professor Health Sciences

Treatment as Antimicrobial Stewardship Project


Rifampicin resistant- tuberculosis (Rr-TB) is estimated to cause 13% of all antimicrobial resistance-attributable deaths worldwide and is driven by both ongoing resistance acquisition and person-to-person transmission. Bedaquiline (BDQ), a new drug, is strongly recommended for Rr-TB treatment since 2018. In this very short time, BDQ resistance has proliferated. For Rr-TB with presumed or confirmed BDQ resistance (BDQr/Rr-TB) there is no evidence-based regimen. The current practice, continue failing regimens, imperils the potency of the remaining RR-TB drug arsenal.

Tuberculosis Antimicrobial Stewardship Program (TASP) tests an Rr-TB antimicrobial stewardship program focusing on rapidly reducing the bacillary load in patients with BDQr/Rr-TB. In 125 patients with BDQr/Rr-TB, enrolled in a trial in Nigeria and Mozambique, treatment will include an empirical highly bactericidal intensive phase followed by rational drug susceptibility test-informed regimen construction.

A pharmacokinetics study will guide dosing of TB drugs. Baseline and acquired resistance will be monitored and the project will evaluate a novel quantitative phenotypic method (thin layer agar), applicable at biosafety level 2 in
high burden, low- and middle-income settings, also to monitor treatment response.

Cost-effectiveness for TB-free survival in comparison with usual care will be studied. Combining low-cost materials found in the local market, we will build, deploy and compare two infection-control air filtration prototypes to conventional bio-aerosol samplers for resistance surveillance.

The anticipated impact of TASP is a cost-effective TB antimicrobial stewardship programme that reduces further resistance development and salvages the current all-oral BDQ regimens for future patients with Rr-TB.

project partners
  • Institute of Tropical Medicine (ITM) (lead), Belgium
  • Universiteit Antwerpen , Belgium
  • Uppsala University, Sweden
  • University of Ibadan, Nigeria
  • Lagos State Univeristy of Science and Technology, Nigeria
  • Fundacao Aurum, Mozambique 
  • University of Rwanda, Rwanda
  • Centre National Hospitalier de Pneumo-phtisiologie,  Benin
  • University of Cape Town, South Africa
  • Aurum Institute NPC, South Africa
  • University of Toronto, Canada
2025 - 2030