@article{Brown2023,
abstract = {Background. Emerging resistance to bedaquiline (BDQ) threatens to undermine advances in the treatment of drug-resistant tuberculosis (DRTB). 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. Methods. We measured mycobacteria growth indicator tube (MGIT)-based 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 {\textgreater}1 collected before or after starting treatment (95 total Mtb isolates from 24 participants). Results. Sixteen of 24 participants had BDQ-resistant TB (MGIT MIC ≥4 µg/mL) and 8 had BDQ-intermediate infections (MGIT MIC = 2 µg/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 {\textless}5 single nucleotide polymorphisms, concerning for potential transmitted BDQ resistance. Conclusions. 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.},
author = {Brown, Tyler S and Tang, Linrui and Omar, Shaheed Vally and Joseph, Lavania and Meintjes, Graeme A and Maartens, Gary and Wasserman, Sean and Shah, N Sarita and Farhat, Maha R and Gandhi, Neel R and Ismail, Nazir and Brust, James C M and Mathema, Barun},
doi = {10.1093/CID/CIAD596},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Brown et al. - 2023 - Genotype–phenotype characterization of serial iMycobacterium tuberculosisi isolates in bedaquiline-resistant tuber.pdf:pdf},
issn = {1058-4838},
journal = {Clinical Infectious Diseases},
keywords = {OA,bedaquiline,drug resistance,fund{\_}ack,original,tuberculosis,whole-genome sequencing},
mendeley-tags = {OA,fund{\_}ack,original},
month = {oct},
pages = {ciad596},
pmid = {37874928},
title = {{Genotype–phenotype characterization of serial \textit{Mycobacterium tuberculosis} isolates in bedaquiline-resistant tuberculosis}},
url = {https://dx.doi.org/10.1093/cid/ciad596},
year = {2023}
}

{"_id":"zAjaX4YYpXEEysMKF","bibbaseid":"brown-tang-omar-joseph-meintjes-maartens-wasserman-shah-etal-genotypephenotypecharacterizationofserialimycobacteriumtuberculosisiisolatesinbedaquilineresistanttuberculosis-2023","author_short":["Brown, T. S","Tang, L.","Omar, S. V.","Joseph, L.","Meintjes, G. A","Maartens, G.","Wasserman, S.","Shah, N S.","Farhat, M. R","Gandhi, N. R","Ismail, N.","Brust, J. C M","Mathema, B."],"bibdata":{"bibtype":"article","type":"article","abstract":"Background. Emerging resistance to bedaquiline (BDQ) threatens to undermine advances in the treatment of drug-resistant tuberculosis (DRTB). 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. Methods. We measured mycobacteria growth indicator tube (MGIT)-based 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 \\textgreater1 collected before or after starting treatment (95 total Mtb isolates from 24 participants). Results. Sixteen of 24 participants had BDQ-resistant TB (MGIT MIC ≥4 µg/mL) and 8 had BDQ-intermediate infections (MGIT MIC = 2 µg/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 \\textless5 single nucleotide polymorphisms, concerning for potential transmitted BDQ resistance. Conclusions. 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.","author":[{"propositions":[],"lastnames":["Brown"],"firstnames":["Tyler","S"],"suffixes":[]},{"propositions":[],"lastnames":["Tang"],"firstnames":["Linrui"],"suffixes":[]},{"propositions":[],"lastnames":["Omar"],"firstnames":["Shaheed","Vally"],"suffixes":[]},{"propositions":[],"lastnames":["Joseph"],"firstnames":["Lavania"],"suffixes":[]},{"propositions":[],"lastnames":["Meintjes"],"firstnames":["Graeme","A"],"suffixes":[]},{"propositions":[],"lastnames":["Maartens"],"firstnames":["Gary"],"suffixes":[]},{"propositions":[],"lastnames":["Wasserman"],"firstnames":["Sean"],"suffixes":[]},{"propositions":[],"lastnames":["Shah"],"firstnames":["N","Sarita"],"suffixes":[]},{"propositions":[],"lastnames":["Farhat"],"firstnames":["Maha","R"],"suffixes":[]},{"propositions":[],"lastnames":["Gandhi"],"firstnames":["Neel","R"],"suffixes":[]},{"propositions":[],"lastnames":["Ismail"],"firstnames":["Nazir"],"suffixes":[]},{"propositions":[],"lastnames":["Brust"],"firstnames":["James","C","M"],"suffixes":[]},{"propositions":[],"lastnames":["Mathema"],"firstnames":["Barun"],"suffixes":[]}],"doi":"10.1093/CID/CIAD596","file":":C$\\$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Brown et al. - 2023 - Genotype–phenotype characterization of serial iMycobacterium tuberculosisi isolates in bedaquiline-resistant tuber.pdf:pdf","issn":"1058-4838","journal":"Clinical Infectious Diseases","keywords":"OA,bedaquiline,drug resistance,fund_ack,original,tuberculosis,whole-genome sequencing","mendeley-tags":"OA,fund_ack,original","month":"oct","pages":"ciad596","pmid":"37874928","title":"Genotype–phenotype characterization of serial <i>Mycobacterium tuberculosis</i> isolates in bedaquiline-resistant tuberculosis","url":"https://dx.doi.org/10.1093/cid/ciad596","year":"2023","bibtex":"@article{Brown2023,\r\nabstract = {Background. Emerging resistance to bedaquiline (BDQ) threatens to undermine advances in the treatment of drug-resistant tuberculosis (DRTB). 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. Methods. We measured mycobacteria growth indicator tube (MGIT)-based 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 {\\textgreater}1 collected before or after starting treatment (95 total Mtb isolates from 24 participants). Results. Sixteen of 24 participants had BDQ-resistant TB (MGIT MIC ≥4 µg/mL) and 8 had BDQ-intermediate infections (MGIT MIC = 2 µg/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 {\\textless}5 single nucleotide polymorphisms, concerning for potential transmitted BDQ resistance. Conclusions. 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.},\r\nauthor = {Brown, Tyler S and Tang, Linrui and Omar, Shaheed Vally and Joseph, Lavania and Meintjes, Graeme A and Maartens, Gary and Wasserman, Sean and Shah, N Sarita and Farhat, Maha R and Gandhi, Neel R and Ismail, Nazir and Brust, James C M and Mathema, Barun},\r\ndoi = {10.1093/CID/CIAD596},\r\nfile = {:C$\\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Brown et al. - 2023 - Genotype–phenotype characterization of serial iMycobacterium tuberculosisi isolates in bedaquiline-resistant tuber.pdf:pdf},\r\nissn = {1058-4838},\r\njournal = {Clinical Infectious Diseases},\r\nkeywords = {OA,bedaquiline,drug resistance,fund{\\_}ack,original,tuberculosis,whole-genome sequencing},\r\nmendeley-tags = {OA,fund{\\_}ack,original},\r\nmonth = {oct},\r\npages = {ciad596},\r\npmid = {37874928},\r\ntitle = {{Genotype–phenotype characterization of serial \\textit{Mycobacterium tuberculosis} isolates in bedaquiline-resistant tuberculosis}},\r\nurl = {https://dx.doi.org/10.1093/cid/ciad596},\r\nyear = {2023}\r\n}\r\n","author_short":["Brown, T. 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C M","Mathema, B."],"key":"Brown2023","id":"Brown2023","bibbaseid":"brown-tang-omar-joseph-meintjes-maartens-wasserman-shah-etal-genotypephenotypecharacterizationofserialimycobacteriumtuberculosisiisolatesinbedaquilineresistanttuberculosis-2023","role":"author","urls":{"Paper":"https://dx.doi.org/10.1093/cid/ciad596"},"keyword":["OA","bedaquiline","drug resistance","fund_ack","original","tuberculosis","whole-genome sequencing"],"metadata":{"authorlinks":{}}},"bibtype":"article","biburl":"https://drive.google.com/uc?export=download&id=1-JLqZ7RwZ3VC2d6ErLGHAtOeMRS_7GCz","dataSources":["Krmt6gt9ktB2s6ARh"],"keywords":["oa","bedaquiline","drug resistance","fund_ack","original","tuberculosis","whole-genome sequencing"],"search_terms":["genotype","phenotype","characterization","serial","mycobacterium","tuberculosis","isolates","bedaquiline","resistant","tuberculosis","brown","tang","omar","joseph","meintjes","maartens","wasserman","shah","farhat","gandhi","ismail","brust","mathema"],"title":"Genotype–phenotype characterization of serial <i>Mycobacterium tuberculosis</i> isolates in bedaquiline-resistant tuberculosis","year":2023}