Management of difficult multidrug‐resistant tuberculosis and extensively drug‐resistant tuberculosis: Update 2012

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.