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Characterizing serial Mycobacterium tuberculosis (Mtb) isolates collected during BDQ-based treatment can provide insights into the etiologies of BDQ resistance in this important group of DRTB patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We measured mycobacteria growth indicator tube (MGIT)\u2013based BDQ minimum inhibitory concentrations (MICs) of Mtb isolates collected from 195 individuals with no prior BDQ exposure who were receiving BDQ-based treatment for DRTB. We conducted whole-genome sequencing on serial Mtb isolates from all participants who had any isolate with a BDQ MIC &amp;gt;1 collected before or after starting treatment (95 total Mtb isolates from 24 participants).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Sixteen of 24 participants had BDQ-resistant TB (MGIT MIC \u22654\u2005\u00b5g\/mL) and 8 had BDQ-intermediate infections (MGIT MIC = 2 \u00b5g\/mL). Participants with pre-existing resistance outnumbered those with resistance acquired during treatment, and 8 of 24 participants had polyclonal infections. BDQ resistance was observed across multiple Mtb strain types and involved a diverse catalog of mmpR5 (Rv0678) mutations, but no mutations in atpE or pepQ. Nine pairs of participants shared genetically similar isolates separated by &amp;lt;5 single nucleotide polymorphisms, concerning for potential transmitted BDQ resistance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>BDQ-resistant TB can arise via multiple, overlapping processes, including transmission of strains with pre-existing resistance. Capturing the within-host diversity of these infections could potentially improve clinical diagnosis, population-level surveillance, and molecular diagnostic test development.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cid\/ciad596","type":"journal-article","created":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T16:38:20Z","timestamp":1696005500000},"page":"269-276","source":"Crossref","is-referenced-by-count":22,"title":["Genotype\u2013Phenotype Characterization of Serial\n                    <i>Mycobacterium tuberculosis<\/i>\n                    Isolates in Bedaquiline-Resistant Tuberculosis"],"prefix":"10.1093","volume":"78","author":[{"given":"Tyler S","family":"Brown","sequence":"first","affiliation":[{"name":"Section of Infectious Diseases, Boston University School of Medicine , Boston, Massachusetts ,","place":["USA"]},{"name":"Center for Communicable Disease Dynamics, Harvard T.H. 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