Clinical management of adults and children with multidrug-resistant and extensively drug-resistant tuberculosis

Globally there is a burgeoning epidemic of drug monoresistant tuberculosis (TB), multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB). Almost 20% of all TB strains worldwide are resistant to at least one major TB drug, including isoniazid. In several parts of the world there is an increasing incidence of MDR-TB, and alarmingly, almost a third of MDR-TB cases globally are resistant to either a fluoroquinolone or aminoglycoside. This trend cannot be ignored because drug-resistant TB is associated with greater morbidity compared to drug-susceptible TB, accounts for almost 25% of global TB mortality, is extremely costly to treat, consumes substantial portions of budgets allocated to national TB programmes in TB-endemic countries and is a major threat to healthcare workers, who are already in short supply in resource-poor settings. Even more worrying is the growing epidemic of resistance beyond XDR-TB, including resistance to newer drugs such as bedaquiline and delamanid, as well as the increasing prevalence of programmatically incurable TB in countries like South Africa, Russia, India and China. These developments threaten to reverse the gains already made against TB. Articles related to MDR-TB and XDR-TB found on PubMed in all languages up to September 2016, published reviews, and files of the authors. To review the clinical management of adults and children with MDR- and XDR-TB with a particular emphasis on the utility of newer and repurposed drugs such as linezolid, bedaquiline and delamanid, as well as management of MDR- and XDR-TB in special situations such as in HIV-infected persons and in children. This review informs on the prevention, diagnosis, and clinical management of MDR-TB and XDR-TB.