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Interpretation of Discordant Rifampicin Susceptibility Test Results Obtained Using GeneXpert vs Phenotypic Drug Susceptibility Testing

BACKGROUND: The 3-month difference in turnaround time between Xpert and conventional phenotypic drug susceptibility testing (pDST) causes patient treatment challenges when pDST rifampin (RIF) susceptibility results and earlier Xpert results disagree, resulting in unnecessary tuberculosis (TB) patien...

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Autores principales: Huo, Fengmin, Ma, Yifeng, Liu, Rongmei, Ma, Liping, Li, Shanshan, Jiang, Guanglu, Wang, Fen, Shang, Yuanyuan, Dong, Lingling, Pang, Yu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397830/
https://www.ncbi.nlm.nih.gov/pubmed/32766385
http://dx.doi.org/10.1093/ofid/ofaa279
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author Huo, Fengmin
Ma, Yifeng
Liu, Rongmei
Ma, Liping
Li, Shanshan
Jiang, Guanglu
Wang, Fen
Shang, Yuanyuan
Dong, Lingling
Pang, Yu
author_facet Huo, Fengmin
Ma, Yifeng
Liu, Rongmei
Ma, Liping
Li, Shanshan
Jiang, Guanglu
Wang, Fen
Shang, Yuanyuan
Dong, Lingling
Pang, Yu
author_sort Huo, Fengmin
collection PubMed
description BACKGROUND: The 3-month difference in turnaround time between Xpert and conventional phenotypic drug susceptibility testing (pDST) causes patient treatment challenges when pDST rifampin (RIF) susceptibility results and earlier Xpert results disagree, resulting in unnecessary tuberculosis (TB) patient exposure to toxic second-line drugs. Here, the prevalence of discordant RIF susceptibility test results, specifically Xpert (resistant) vs pDST (susceptible) results, was determined. METHODS: Tuberculosis patients enrolled between January 2015 and June 2018 at Beijing Chest Hospital who consecutively tested positive for RIF resistance using Xpert then negative using pDST were studied. DNA sequences and minimal inhibitory concentration (MIC) results provided insights for understanding discordant results. RESULTS: Of 26( )826 patients with suggestive TB symptoms undergoing Xpert MTB/RIF testing, 728 diagnosed as RIF-resistant were evaluated. Of these, 118 (16.2%) exhibiting Xpert RIF resistance and phenotypic RIF susceptibility yielded 104 successfully subcultured isolates; of these, 86 (82.7%) harbored rpoB gene RIF resistance–determining region mutations and 18 (17.3%) did not. The Leu511Pro (25.0%) and Leu533Pro (17.3%) mutations were most frequently associated with discordant RIF susceptibility test results. Of the 86 isolates with rpoB mutations, 42 (48.8%) with MICs ≤1.0 mg/L were assigned to the RIF-susceptible group, with Leu511Pro being the most common mutation observed. Isolates with a very low bacterial load were most frequently misdiagnosed as RIF-resistant by Xpert. CONCLUSIONS: Approximately one-sixth of RIF-resistant TB isolates identified via Xpert yielded discordant pDST results due to questionable interpretation of specific “disputed” mutations. Thus, a diagnostic flowchart should be used to correctly interpret Xpert RIF resistance results to best guide patient treatment.
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spelling pubmed-73978302020-08-05 Interpretation of Discordant Rifampicin Susceptibility Test Results Obtained Using GeneXpert vs Phenotypic Drug Susceptibility Testing Huo, Fengmin Ma, Yifeng Liu, Rongmei Ma, Liping Li, Shanshan Jiang, Guanglu Wang, Fen Shang, Yuanyuan Dong, Lingling Pang, Yu Open Forum Infect Dis Major Articles BACKGROUND: The 3-month difference in turnaround time between Xpert and conventional phenotypic drug susceptibility testing (pDST) causes patient treatment challenges when pDST rifampin (RIF) susceptibility results and earlier Xpert results disagree, resulting in unnecessary tuberculosis (TB) patient exposure to toxic second-line drugs. Here, the prevalence of discordant RIF susceptibility test results, specifically Xpert (resistant) vs pDST (susceptible) results, was determined. METHODS: Tuberculosis patients enrolled between January 2015 and June 2018 at Beijing Chest Hospital who consecutively tested positive for RIF resistance using Xpert then negative using pDST were studied. DNA sequences and minimal inhibitory concentration (MIC) results provided insights for understanding discordant results. RESULTS: Of 26( )826 patients with suggestive TB symptoms undergoing Xpert MTB/RIF testing, 728 diagnosed as RIF-resistant were evaluated. Of these, 118 (16.2%) exhibiting Xpert RIF resistance and phenotypic RIF susceptibility yielded 104 successfully subcultured isolates; of these, 86 (82.7%) harbored rpoB gene RIF resistance–determining region mutations and 18 (17.3%) did not. The Leu511Pro (25.0%) and Leu533Pro (17.3%) mutations were most frequently associated with discordant RIF susceptibility test results. Of the 86 isolates with rpoB mutations, 42 (48.8%) with MICs ≤1.0 mg/L were assigned to the RIF-susceptible group, with Leu511Pro being the most common mutation observed. Isolates with a very low bacterial load were most frequently misdiagnosed as RIF-resistant by Xpert. CONCLUSIONS: Approximately one-sixth of RIF-resistant TB isolates identified via Xpert yielded discordant pDST results due to questionable interpretation of specific “disputed” mutations. Thus, a diagnostic flowchart should be used to correctly interpret Xpert RIF resistance results to best guide patient treatment. Oxford University Press 2020-07-05 /pmc/articles/PMC7397830/ /pubmed/32766385 http://dx.doi.org/10.1093/ofid/ofaa279 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Major Articles
Huo, Fengmin
Ma, Yifeng
Liu, Rongmei
Ma, Liping
Li, Shanshan
Jiang, Guanglu
Wang, Fen
Shang, Yuanyuan
Dong, Lingling
Pang, Yu
Interpretation of Discordant Rifampicin Susceptibility Test Results Obtained Using GeneXpert vs Phenotypic Drug Susceptibility Testing
title Interpretation of Discordant Rifampicin Susceptibility Test Results Obtained Using GeneXpert vs Phenotypic Drug Susceptibility Testing
title_full Interpretation of Discordant Rifampicin Susceptibility Test Results Obtained Using GeneXpert vs Phenotypic Drug Susceptibility Testing
title_fullStr Interpretation of Discordant Rifampicin Susceptibility Test Results Obtained Using GeneXpert vs Phenotypic Drug Susceptibility Testing
title_full_unstemmed Interpretation of Discordant Rifampicin Susceptibility Test Results Obtained Using GeneXpert vs Phenotypic Drug Susceptibility Testing
title_short Interpretation of Discordant Rifampicin Susceptibility Test Results Obtained Using GeneXpert vs Phenotypic Drug Susceptibility Testing
title_sort interpretation of discordant rifampicin susceptibility test results obtained using genexpert vs phenotypic drug susceptibility testing
topic Major Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397830/
https://www.ncbi.nlm.nih.gov/pubmed/32766385
http://dx.doi.org/10.1093/ofid/ofaa279
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