Tuberculosis Antimicrobial Stewardship Program (TASP): tackling Bedaquiline-resistant tuberculosis

ongoing

In the 2024 updated Bacterial Priority Pathogen list of WHO, Mycobacterium tuberculosis (TB) is a critical priority pathogen, emphasizing the urgent need for action. Rifampicin resistant-tuberculosis (Rr-TB) is estimated to cause 13% of antimicrobial resistance-attributable deaths globally 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 significantly. For Rr-TB at risk of/with BDQ resistance (BDQr/Rr-TB) there is no evidence-based regimen. The current practice, with continued failing regimens, imperils the potency of the remaining Rr-TB drug arsenal. Tuberculosis Antimicrobial Stewardship Program (TASP) aims to rapidly reduce bacillary load in patients at risk/with BDQr/Rr-TB by using an empirical highly bactericidal intensive phase (for those at risk) followed by drug-susceptibility testing (DST)-informed artificial intelligence (AI)-aided Treatment Recommender's regimen composition. 125 participants at risk/with BDQr/Rr-TB will be enrolled in Nigeria, Mozambique and South Africa. Baseline and acquired resistance will be monitored and a novel, fast and quantitative phenotypic method (thin layer agar), with little infrastructural requirements, will be evaluated in TASP’s high burden, limited resource settings through decentralized implementation. Additionally, TASP will improve environmental control with co-designed, portable air cleaners, built sourcing low-cost materials from the local market. Filter waste products will be used for resistance surveillance and compared to conventional bio-aerosol samplers. 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 the future.