The Emergence of Extensively Drug‐Resistant Tuberculosis: A Global Health Crisis Requiring New Interventions: Part I: The Origins and Nature of the Problem

Abstract

Surveillance studies and outbreak investigations indicate that an extensively drug-resistant (XDR) form of tuberculosis (TB) is increasing in prevalence worldwide. In outbreak settings among HIV-infected, there is a high-case fatality rate. Better outcomes occur in HIVuninfected, particularly if drug susceptibility test (DST) results are available rapidly to allow tailoring of drug therapy. This review will be presented in two segments. The first characterizes the problem posed by XDR-TB, addressing the epidemiology and evolution of XDR-TB and treatment outcomes. The second reviews technologic advances that may contribute to the solution, new diagnostics, and advances in understanding drug resistance and in the development of new drugs.

Mycobacterium tuberculosis mutants with multidrug resistance: History of origin, genetic and molecular mechanisms of resistance, and emerging challenges

“…For instance, the proportions of MDR isolates in the two patient groups were 14.8 and 44.7% in Arkhan gelsk oblast [12] and 12 and 40% in Karakalpakskii raion of Uzbekistan [13]. The number of MDR iso lates increased three to fourfold from 2000 to 2007 [5,14]. Data collected in 2004 from 184 countries were summarized in [15].…”

“…Although documented cases of XDR tuberculosis are relatively few in the global population, XDR tuber culosis was considered in 228 published works by 2009 (according to [11]), including several reviews referred to above [5,14,18,20,[26][27][28]. Cases of XDR tuber culosis were registered in 49 countries as of September 2009 [18].…”

Mycobacteriophages as Potential Therapeutic Agents against Drug-Resistant Tuberculosis

“…When active TB disease is developed, the standard treatment consists of a 6-month regimen using a combination of four first-line drugs (isoniazid, rifampicin, ethambutol, and pyrazinamide) that, although very efficient, can promote the emergence of resistance in the absence of sufficient healthcare infrastructure and patient poor adherence to therapy [ 4 ]. As a direct consequence, in the past two decades, multi (MDR), extensively (XDR), extremely (XXDR), and total (TDR) drug-resistant M. tuberculosis strains have emerged worldwide as a threat to public health and TB control, especially in TB endemic areas [ 5 , 6 , 7 ]. MDR strains are defined as resistant to at least the two first-line drugs isoniazid and rifampicin, whereas XDR, first reported in 2006 in South Africa, are resistant to isoniazid and rifampicin plus any fluoroquinolone, and at least one of the three injectable second-line drugs (amikacin, kanamycin, or capreomycin) [ 8 ].…”

Mycobacterium Strain and Type of Resistance in Pulmonary Tuberculosis Patients: A Missed Link in Iran’s National Tuberculosis Plan

“…Using molecular methods for identification of mutations in the genes may offer means for rapid screening of the drug resistance among the MTB isolates and initiation of early treatment (23,24).…”