Multidrug-resistant tuberculous meningitis is now appearing worldwide, including in the United States, and is difficult to diagnose and treat. We discuss methods to diagnose tuberculous meningitis, review current and experimental assays for determining drug resistance, and consider approaches to management of the patient. We review the epidemiology of multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis in both pulmonary and meningeal infections, discuss promising molecular methods for determining drug resistance, and review current approaches toward treatment of patients. The incidence of multidrug-resistant tuberculous meningitis is increasing, and diagnosing and treating these patients will be a major challenge. There is a need to improve rapid methods of isolating the organism from cerebrospinal fluid, to advance molecular methods to rapidly test the isolate for antibiotic sensitivity, and to develop new antituberculosis drugs, especially ones that cross the blood-cerebrospinal fluid barrier.
