Epidemiology of extensively drug-resistant tuberculosis
- Scott K Heysell, MD, MPH
Scott K Heysell, MD, MPH
- Assistant Professor, Infectious Diseases and International Health
- University of Virginia
- Gerald Friedland, MD
Gerald Friedland, MD
- Professor of Medicine and Epidemiology
- Yale University
Mycobacterium tuberculosis is an ancient human pathogen, which has plagued countless human societies despite the introduction of curative and preventive therapy in the last century . In recent years, international attention has turned toward the evolving burden of drug resistance. Multidrug-resistant tuberculosis (MDR-TB) has emerged in epidemic proportions in the wake of widespread HIV infection in the world's poorest populations, including sub-Saharan Africa. Extensively drug-resistant tuberculosis (XDR-TB) was first reported in 2006 but has now been documented on six continents . These trends are critically important for global health, since drug-resistant tuberculosis (TB) mortality rates are high and second- and third-line agents for the treatment of drug-resistant TB are less potent and less tolerable than first-line therapies.
This topic will focus specifically on the epidemiology and clinical features of XDR-TB. Information on MDR-TB, drug-susceptible TB, and the diagnosis of tuberculosis are discussed in detail elsewhere. (See "Clinical manifestations and complications of pulmonary tuberculosis" and "Epidemiology, clinical manifestations, and diagnosis of tuberculosis in HIV-infected patients" and "Diagnosis, treatment, and prevention of drug-resistant tuberculosis" and "Diagnosis and treatment of extensively drug-resistant tuberculosis".)
Multidrug-resistant tuberculosis (MDR-TB) is defined as laboratory-confirmed resistance to the two most potent first-line medications, isoniazid and rifampin . Since 2007, extensively drug-resistant tuberculosis (XDR-TB) has been defined as resistance to both isoniazid and rifampin with additional resistance to at least one fluoroquinolone and one injectable agent (amikacin, kanamycin, or capreomycin) [4,5].
M. tuberculosis strains resistant to all locally tested medications have been defined as "totally drug-resistant" (TDR-TB) [6,7]. However, these TDR isolates were not tested against a complete panel of second-line antituberculosis drugs, including cycloserine, terizidone, clofazimine, linezolid, the carbapenems, and the novel agents bedaquiline and delamanid. Regardless, reports of TDR-TB raise epidemiologic concerns regarding the ability to track complex resistance patterns in resource-limited settings . The emergence of TDR-TB also highlights the limited availability of susceptibility testing for the less commonly used antituberculosis drugs, the concern for amplified drug resistance in the face of weakly potent drug combinations, the relative inability to predict synergy or drug activity at the site of infection, and the need for optimized pharmacokinetic strategies and entirely new antituberculosis drug regimens.
ESTIMATES OF XDR-TB DRUG RESISTANCE
Drug resistance was first noted in the 1940s when streptomycin was formally studied as monotherapy for the treatment of tuberculosis . As a result, subsequent therapeutic interventions utilized multidrug regimens to decrease the risk of drug resistance.
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- ESTIMATES OF XDR-TB DRUG RESISTANCE
- Tugela Ferry
- United States
- GENERAL PRINCIPLES OF DRUG RESISTANCE
- Acquired versus primary drug resistance
- Prevention and management of primary versus acquired drug resistance
- - Geographic distribution of primary versus acquired resistance
- RISK FACTORS FOR DRUG RESISTANCE
- Adherence and other factors
- Historical clues
- Healthcare workers
- EFFECT OF HIV ON TB DRUG RESISTANCE
- COMMON GENETIC MUTATIONS
- SUMMARY AND RECOMMENDATIONS