P112
Determining Epidemiological Cut-Off Values for BTZ-043 and Ganfeborole Using the EUCAST Reference Method
A Ghodousi(1,2) S Andres(3) E Terschlüsen(4) F Saluzzo(1) C Kallenberg(3) I Friesen(3) J van Ingen(4) D M Cirillo(2)
1:University Vita-Salute San Raffaele; 2:San Raffael Scientific Institute; 3:National and World Health Organization Supranational Reference Laboratory for Mycobacteria, Research Center Borstel, Leibniz Lung Center, Borstel, 23845, Germany; 4:Radboud University Medical Center
Background:
Tuberculosis (TB) remains a significant global health challenge, particularly with the rise of drug-resistant strains. The introduction of novel anti-TB drugs like BTZ-043 and Ganfeborole offers promising treatment options. Both drugs are currently in Phase 2B clinical trials, and establishing reliable susceptibility thresholds before their introduction into clinical use is crucial. The EUCAST reference method enables the determination of Epidemiological Cut-Off Values (ECOFFs) to differentiate wild-type strains from resistant strains of Mycobacterium tuberculosis complex (MTBC).
Objective:
To determine the tentative ECOFFs for BTZ-043 and Ganfeborole using the EUCAST reference method, based on the H37Rv reference strain and clinical wild-type MTBC strains, tested across three laboratories.
Methods:
The study was conducted across three laboratories for both Ganfeborole and BTZ-043. A total of 124 independent cultures of H37Rv reference strain and 130 clinical MTBC isolates were tested using the EUCAST broth microdilution method to determine the Minimum Inhibitory Concentration (MIC) for each drug. ECOFFs were calculated by analyzing MIC distributions and applying statistical methods, including ECOFFinder, to distinguish wild-type from non-wild-type strains.
Results:
The tentative ECOFFs for Ganfeborole were 0.0625 µg/mL (95% confidence) and 0.125 µg/mL (99.9% confidence). For BTZ-043, the tentative ECOFFs were 0.004 µg/mL (95% confidence) and 0.008 µg/mL (99.9% confidence).
Conclusion:
The established tentative ECOFFs provide essential thresholds for susceptibility testing and are crucial for monitoring TB drug resistance. These values will support the clinical application of these agents, ensuring that a reliable reference method for performing drug susceptibility testing is available upon their clinical use.