Implementing Best Practises on Data Generation and Reporting of Mycobacterium tuberculosis Time Kill Assays: A Case Study of Standardized Protocol Within the ERA4TB Consortium

Tuberculosis (TB) is the deadliest infectious disease after COVID-19. The European Regimen Accelerator for Tuberculosis (ERA4TB) is a public-private partnership of more than 30 institutions with the objective to progress new anti-TB regimens into the clinic. Thus, robust and replicable results across independent laboratories are essential for reliable interpretation of treatment efficacy. Time-kill assays provide essential input data for pharmacometric model informed translation of single agents and regimens activity from in vitro to in vivo and clinic. An ERA4TB standardization workgroup was established to unify time-kill assay protocols and data reporting templates. Five conditions were assessed in six independent laboratories using four bacterial plating methods. Baseline bacterial burden varied between laboratories but variability was limited in net drug effect, confirming 2.5 µL equally robust as 100 µL plating. This exercise establishes the foundations of collaborative efforts for robust data generation, reporting and integration within the overarching Antimicrobial Resistance Accelerator programme.Funding Information: The project leading to this publication has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 853989. The JU receives support from the European Union’s Horizon 2020 Research and Innovation Programme and EFPIA and Global Alliance for TB Drug Development Non-Profit Organisation, Bill & Melinda Gates Foundation, University of Dundee.Conflict of Interests: The authors declare no competing interests.