Wild-type MIC distribution and evaluation of epidemiological cut-offs of second-line TB-drugs in susceptible and MDR-TB clinical isolates from Chennai, India
Abstract
Introduction: The rise of drug-resistant tuberculosis poses a significant challenge in patient management. Epidemiological cut-off values define drug resistance in Mycobacterium tuberculosis. In our previous study, we reported deviations from the WHO-recommended epidemiological cut-off values and identified subtherapeutic concentrations of rifampicin in clinical Mycobacterium tuberculosis isolates. Building on these findings, the present study systematically evaluated the epidemiological cut-off values and pharmacodynamic profiles of newer and repurposed second-line anti-TB drugs - Bedaquiline, Delamanid, Moxifloxacin, Linezolid, Clofazimine, Levofloxacin, and Pretomanid against the first-line drug-sensitive and isolates that are resistant to Rifampicin and Isoniazid from tuberculosis patients in and around Chennai.
Methods: The Broth microdilution-based Microscopic Observation Drug Susceptibility assay was employed to determine the minimum inhibitory concentration of the drugs against well-characterized wild-type and drug-resistant clinical Mycobacterium tuberculosis clinical isolates. The resulting MIC profiles were subsequently analyzed to delineate pharmacodynamic relationships underlying therapeutic efficacy and resistance development.
Results and discussion: Deviations from the World Health Organization-recommended epidemiological cut-off values were observed, with lower thresholds for delamanid and levofloxacin and higher concentrations for clofazimine and…
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