Therapy of Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis

The global epidemic of multidrug-resistant tuberculosis (MDR-TB) caused by Mycobacterium tuberculosis strains resistant to at least isoniazid and rifampin was recently reported as larger than previously estimated, with at least 580,000 new cases reported in 2015. Extensively drug-resistant tuberculosis (XDR-TB), MDR-TB with additional resistance to a second-line fluoroquinolone and injectable, continues to account for nearly 10% of MDR cases globally. Cases in India, China, and the Russian Federation account for >45% of the cases of MDR-TB. Molecular testing helps identify MDR more quickly, and treatment options have expanded across the globe. Despite this, only 20% are in treatment, and treatment is challenging due to the toxicity of medications and the long duration. In 2016 the World Health Organization updated guidelines for the treatment of MDR-TB. A new short-course regimen is an option for those who qualify. Five effective drugs, including pyrazinamide (PZA) when possible, are recommended during the initial treatment phase and four drugs thereafter. Revised drug classifications include the use of linezolid and clofazimine as key second-line drugs and the option to use bedaquiline and delamanid to complete a five-drug regimen when needed due to poor medication tolerance or extensive resistance. Despite multiple drugs and long-duration treatment regimens, the outcomes for MDR and especially XDR-TB are much worse than for drug-susceptible disease. Better management of toxicity, prevention of transmission, and identification and appropriate management of infected contacts are important challenges for the future.