title: Isoniazid-resistant tuberculosis: a cause for concern?
abstract: The drug isoniazid (INH) is a key component of global tuberculosis (TB) control programmes. It is estimated, however, that 16.1% of TB disease cases in the former Soviet Union countries and 7.5% of cases outside of these settings have non-multidrug-resistant (MDR) INH resistance. Resistance has been linked to poorer treatment outcomes, post-treatment relapse and death, at least for specific sites of disease. Multiple genetic loci are associated with phenotypic resistance; however, the relationship between genotype and phenotype is complex, and restricts the use of rapid sequencing techniques as part of the diagnostic process to determine the most appropriate treatment regimens for patients. The burden of resistance also influences the usefulness of INH preventive therapy. Despite seven decades of INH use, our knowledge in key areas such as the epidemiology of resistant strains, their clinical consequences, whether tailored treatment regimens are required and the role of INH resistance in fuelling the MDR-TB epidemic is limited. The importance of non-MDR INH resistance needs to be re-evaluated both globally and by national TB control programmes.
authors.affiliation: Institute of Global Health, UCL, London, UK.
authors.forename: H R
authors.initials: HR
authors.lastname: Stagg
authors.affiliation: University College London (UCL) Respiratory, Division of Medicine, UCL, London, UK;, Royal Free London National Health Service Foundation Trust, London, UK.
authors.forename: M C
authors.initials: MC
authors.lastname: Lipman
authors.affiliation: Centre for Clinical Microbiology, UCL, London, UK.
authors.forename: T D
authors.initials: TD
authors.lastname: McHugh
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.
authors.forename: H E
authors.initials: HE
authors.lastname: Jenkins
mesh_terms: D000995:Antitubercular Agents / Q000627:therapeutic use*; D005838:Genotype; D014943:Global Health; D006801:Humans; D007538:Isoniazid / Q000627:therapeutic use*; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D009313:National Health Programs; D010641:Phenotype; D016896:Treatment Outcome; D014376:Tuberculosis / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology
chemical_list: D000995:Antitubercular Agents; D007538:Isoniazid