title: Clinical implications of molecular drug resistance testing for Mycobacterium tuberculosis: a TBNET/RESIST-TB consensus statement.
abstract: The emergence of drug-resistant strains of Mycobacterium tuberculosis is a challenge to global tuberculosis (TB) control. Although culture-based methods have been regarded as the gold standard for drug susceptibility testing (DST), molecular methods provide rapid information on mutations in the M. tuberculosis genome associated with resistance to anti-tuberculosis drugs. We ascertained consensus on the use of the results of molecular DST for clinical treatment decisions in TB patients. This document has been developed by TBNET and RESIST-TB groups to reach a consensus about reporting standards in the clinical use of molecular DST results. Review of the available literature and the search for evidence included hand-searching journals and searching electronic databases. The panel identified single nucleotide mutations in genomic regions of M. tuberculosis coding for katG, inhA, rpoB, embB, rrs, rpsL and gyrA that are likely related to drug resistance in vivo. Identification of any of these mutations in clinical isolates of M. tuberculosis has implications for the management of TB patients, pending the results of in vitro DST. However, false-positive and false-negative results in detecting resistance-associated mutations in drugs for which there is poor or unproven correlation between phenotypic and clinical drug resistance complicate the interpretation. Reports of molecular DST results should therefore include specific information on the mutations identified and provide guidance for clinicians on interpretation and on the choice of the appropriate initial drug regimen.
authors.affiliation: <sup>*</sup>Institut d'Investigació Germans Trias i Pujol, Centro de Investigación Biomédica en Red Enfermedades Respiratorias, Universitat Autònoma de Barcelona, Badalona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Domínguez
authors.affiliation: Institute of Medical Microbiology, National Centre for Mycobacteria, University of Zurich, Zurich, Switzerland.
authors.forename: E C
authors.initials: EC
authors.lastname: Boettger
authors.affiliation: TB Supranational Reference Laboratory, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Cirillo
authors.affiliation: TB Supranational Reference Laboratory, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Cobelens
authors.affiliation: University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: K D
authors.initials: KD
authors.lastname: Eisenach
authors.affiliation: Swiss Tropical and Public Health Institute, University of Basel, Basel, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Gagneux
authors.affiliation: National Reference Center for Mycobacteria, German Center for Infection Research (DZIF) Tuberculosis Unit, Research Center Borstel, Borstel, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Hillemann
authors.affiliation: Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts, USA.
authors.forename: R
authors.initials: R
authors.lastname: Horsburgh
authors.affiliation: Institut d'Investigació Germans Trias i Pujol, Centro de Investigación Biomédica en Red Enfermedades Respiratorias, Universitat Autònoma de Barcelona, Badalona, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Molina-Moya
authors.affiliation: Division of Molecular Mycobacteriology, DZIF Tuberculosis Unit, Research Center Borstel, Borstel, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Niemann
authors.affiliation: Emerging Bacterial Pathogens Unit, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Tortoli
authors.affiliation: Emerging Bacterial Pathogens Unit, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Whitelaw
authors.affiliation: Division of Clinical Infectious Diseases, DZIF Tuberculosis Unit, Research Center Borstel, Borstel, Germany; Department of Medicine, University of Namibia School of Medicine, Windhoek, Namibia; Department of Medicine, Karolinska Institute, Stockholm, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Lange
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology; D003245:Consensus Statements as Topic; D006801:Humans; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*
chemical_list: D000995:Antitubercular Agents