The Nature of the Threat
Multidrug-resistant tuberculosis (MDR TB) is caused by bacteria resistant to isoniazid and rifampicin, the two most effective first-line anti-TB drugs, originally introduced in the 1950s.
Extensively drug-resistant tuberculosis (XDR TB) is resistant to the same drugs as MDR TB (isoniazid and rifampicin), as well as any fluoroquinolone (levofloxacin, moxifloxacin, or ofloxacin) and at least one second-line injectable drug (kanamycin, amikacin, or capreomycin).
Totally drug-resistant tuberculosis (TDR TB) is TB for which no effective treatments are available.
Pathways for Infection
MDR/XDR TB results from either primary infection with a drug-resistant strain of TB (i.e., transmitted by person-to-person contact) or acquired infection with such a strain that occurs in the course of a patient’s treatment, resulting, for example, from failure to ensure regular treatment with high-quality drugs. Amplified resistance, or the enhancement of existing drug resistance as a result of initiating an inappropriate drug regimen at the beginning of care, is a significant challenge created by providing an incorrect combination of drugs. Even when an empirically appropriate drug regimen is selected at the beginning of treatment, by the time drug susceptibility information is available, resistance may be amplified.
Treatment of MDR and XDR TB requires 2 years or more of daily, directly observed treatment with drugs that are less potent, more toxic, and much more expensive than those used to treat drug-susceptible TB. Despite the challenges, aggressive treatment with second-line drugs has produced successful outcomes in MDR and XDR TB patients. However, TDR TB is a growing threat. The spread of TDR TB is especially ominous as it would return the globe to the pre-antibiotic era with respect to this disease. Identifying and addressing barriers to effective and timely diagnosis and treatment of drug-resistant TB supports prevention of the further emergence of strains of TB with broad-spectrum resistance (Keshavjee and Seung, 2008).
aThe information in this box was originally presented at the Forum’s 2008 workshop on drug-resistant TB (IOM, 2009).