title: Management of difficult multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis: update 2012.
abstract: Multidrug-resistant (MDR) tuberculosis (TB) denotes bacillary resistance to at least isoniazid and rifampicin. Extensively drug-resistant (XDR) TB is MDR-TB with additional bacillary resistance to any fluoroquinolone and at least one second-line injectable drugs. Rooted in inadequate TB treatment and compounded by a vicious circle of diagnostic delay and improper treatment, MDR-TB/XDR-TB has become a global epidemic that is fuelled by poverty, human immunodeficiency virus (HIV) and neglect of airborne infection control. The majority of MDR-TB cases in some settings with high prevalence of MDR-TB are due to transmission of drug-resistant bacillary strains to previously untreated patients. Global efforts in controlling MDR-TB/XDR-TB can no longer focus solely on high-risk patients. It is difficult and costly to treat MDR-TB/XDR-TB. Without timely implementation of preventive and management strategies, difficult MDR-TB/XDR-TB can cripple global TB control efforts. Preventive strategies include prompt diagnosis with adequate TB treatment using the directly observed therapy, short-course (DOTS) strategy and drug-resistance programmes, airborne infection control, preventive treatment of TB/HIV, and optimal use of antiretroviral therapy. Management strategies for established cases of difficult MDR-TB/XDR-TB rely on harnessing existing drugs (notably newer generation fluoroquinolones, high-dose isoniazid, linezolid and pyrazinamide with in vitro activity) in the best combinations and dosing schedules, together with adjunctive surgery in carefully selected cases. Immunotherapy may also have a role in the future. New diagnostics, drugs and vaccines are required to meet the challenge, but science alone is insufficient. Difficult MDR-TB/XDR-TB cannot be tackled without achieving high cure rates with quality DOTS and beyond, and concurrently addressing poverty and HIV.
authors.affiliation: Department of Health, Tuberculosis and Chest Service, the Chinese University of Hong Kong, Hong Kong, China. kc_chang@dh.gov.hk
authors.forename: Kwok-Chiu
authors.initials: KC
authors.lastname: Chang
authors.forename: Wing-Wai
authors.initials: WW
authors.lastname: Yew
mesh_terms: D000995:Antitubercular Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D054908:Extensively Drug-Resistant Tuberculosis / Q000188:drug therapy / Q000453:epidemiology; D006801:Humans; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy* / Q000453:epidemiology
chemical_list: D000995:Antitubercular Agents