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Genotype-Phenotype Characterization of Serial Mycobacterium tuberculosis Isolates in Bedaquiline-Resistant Tuberculosis.
Brown, Tyler S; Tang, Linrui; Omar, Shaheed Vally; Joseph, Lavania; Meintjes, Graeme; Maartens, Gary; Wasserman, Sean; Shah, N Sarita; Farhat, Maha R; Gandhi, Neel R; Ismail, Nazir; Brust, James C M; Mathema, Barun.
Afiliación
  • Brown TS; Section of Infectious Diseases, Boston University School of Medicine, Boston, Massachusetts, USA.
  • Tang L; Center for Communicable Disease Dynamics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
  • Omar SV; Department of Epidemiology, Columbia University Mailman School of Public Health, New York, New York, USA.
  • Joseph L; Centre for Tuberculosis, National Institute for Communicable Diseases, Johannesburg, South Africa.
  • Meintjes G; Department of Molecular Medicine & Hematology, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
  • Maartens G; Centre for Tuberculosis, National Institute for Communicable Diseases, Johannesburg, South Africa.
  • Wasserman S; Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, and Department of Medicine, University of Cape Town, Cape Town, South Africa.
  • Shah NS; Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, and Department of Medicine, University of Cape Town, Cape Town, South Africa.
  • Farhat MR; Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
  • Gandhi NR; Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, and Department of Medicine, University of Cape Town, Cape Town, South Africa.
  • Ismail N; Division of Infectious Diseases and HIV Medicine, Department of Medicine, University of Cape Town, Cape Town, South Africa.
  • Brust JCM; Departments of Epidemiology and Global Health and Medicine, Rollins School of Public Health and Emory School of Medicine, Atlanta, Georgia, USA.
  • Mathema B; Department of Biomedical Informatics, Harvard Medical School, Boston, Massachusetts, USA.
Clin Infect Dis ; 78(2): 269-276, 2024 02 17.
Article en En | MEDLINE | ID: mdl-37874928
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 >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 <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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tuberculosis / Tuberculosis Resistente a Múltiples Medicamentos / Mycobacterium tuberculosis Límite: Humans Idioma: En Revista: Clin Infect Dis Asunto de la revista: DOENCAS TRANSMISSIVEIS Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tuberculosis / Tuberculosis Resistente a Múltiples Medicamentos / Mycobacterium tuberculosis Límite: Humans Idioma: En Revista: Clin Infect Dis Asunto de la revista: DOENCAS TRANSMISSIVEIS Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos