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 HIV-uninfected, 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.

Figure 1

Prevalence of MDR‐TB among new cases of TB, 1994–2002, and countries with at least one reported case of XDR‐TB as of January 2007. Data from World Health Organization. ⁹ Reprinted from Reference 9, with permission.

Figure 2

Development of drug resistance in the KwaZulu‐Natal family of strains of Mycobacterium tuberculosis during the period 1994–2006. Ca = capreomycin, E = ethambutol, Et = ethionamide, F = fluoroquinolones, I = isoniazid, K = kanamycin/amikacin, R = rifampicin, S = streptomycin, T = thiacetazone. Reprinted from Reference 35, with permission.

Figure 3

Survival rates among patients with multidrug‐resistant TB and those with extensively drug‐resistant TB. Retrospective study of 164 patients with MDR‐TB and 10 patients with XDR‐TB treated at National Jewish Medical and Research Center. Kaplan–Meier survival curves estimates are based on the number of deaths from TB or surgery (p < 0.001 by the log‐rank test for the comparison of the two groups). The circles indicate the times of censoring. Reprinted from Reference 46, with permission.

Figure 4

Use of anti‐TB agents in 48 individualized treatment regimens for XDR TB, drug‐susceptibility testing, and prior exposure to a particular agent in Lima, Peru (reprinted from Reference 50, with permission). Some susceptibility testing was performed for these agents. The asterisks indicate that some testing was performed for these agents. However, because of the relative infrequency of testing, as well as the lack of standardization or confirmed clinical relevance of tests for these drugs, clinicians relied less on these results than on those for other drugs. Reprinted from Reference 47, with permission.