title: Multidrug-resistant tuberculosis drug susceptibility and molecular diagnostic testing.
abstract: Multidrug-resistant tuberculosis (MDR TB), defined by resistance to the 2 most effective first-line drugs, isoniazid and rifampin, is on the rise globally and is associated with significant morbidity and mortality. Despite the increasing availability of novel rapid diagnostic tools for Mycobacterium tuberculosis (Mtb) drug susceptibility testing, the clinical applicability of these methods is unsettled. In this study, the mechanisms of action and resistance of Mtb to isoniazid and rifampin, and the utility, advantages and limitations of the available Mtb drug susceptibility testing tools are reviewed, with particular emphasis on molecular methods with rapid turnaround including line probe assays, molecular beacon-based real-time polymerase chain reaction and pyrosequencing. The authors conclude that neither rapid molecular drug testing nor phenotypic methods are perfect in predicting Mtb drug susceptibility and therefore must be interpreted within the clinical context of each patient.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA 30303, USA. akalokh@emory.edu
authors.forename: Ameeta S
authors.initials: AS
authors.lastname: Kalokhe
authors.forename: Majid
authors.initials: M
authors.lastname: Shafiq
authors.forename: James C
authors.initials: JC
authors.lastname: Lee
authors.forename: Susan M
authors.initials: SM
authors.lastname: Ray
authors.forename: Yun F
authors.initials: YF
authors.lastname: Wang
authors.forename: Beverly
authors.initials: B
authors.lastname: Metchock
authors.forename: Albert M
authors.initials: AM
authors.lastname: Anderson
authors.forename: Minh Ly T
authors.initials: ML
authors.lastname: Nguyen
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000627:therapeutic use; D006801:Humans; D007538:Isoniazid / Q000627:therapeutic use; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D009169:Mycobacterium tuberculosis / Q000235:genetics*; D012293:Rifampin / Q000627:therapeutic use; D017422:Sequence Analysis, DNA / Q000379:methods; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*
chemical_list: D000995:Antitubercular Agents; D007538:Isoniazid; D012293:Rifampin