Challenges and Controversies in Defining Totally Drug-Resistant Tuberculosis

Peter Cegielski

, Paul Nunn, Ekaterina V. Kurbatova, Karin Weyer, Tracy L. Dalton, Douglas F. Wares, Michael F. Iademarco, Kenneth G. Castro, and Mario Raviglione

Author affiliations: Author affiliations: Centers for Disease Control and Prevention, Atlanta, Georgia, USA (P. Cegielski, E.V. Kurbatova, T.L. Dalton, M.F. Iademarco, K.G. Castro); World Health Organization, Geneva, Switzerland (P. Nunn, K. Weyer, D.F. Wares, M. Raviglione)

Abstract

In March 2012, in response to reports of tuberculosis (TB) resistant to all anti-TB drugs, the World Health Organization convened an expert consultation that identified issues to be resolved before defining a new category of highly drug-resistant TB. Proposed definitions are ambiguous, and extensive drug resistance is encompassed by the already defined extensively drug-resistant (XDR) TB. There is no evidence that proposed totally resistant TB differs from strains encompassed by XDR TB. Susceptibility tests for several drugs are poorly reproducible. Few laboratories can test all drugs, and there is no consensus list of all anti-TB drugs. Many drugs are used off-label for highly drug resistant TB, and new drugs formulated to combat resistant strains would render the proposed category obsolete. Labeling TB strains as totally drug resistant might lead providers to think infected patients are untreatable. These challenges must be addressed before defining a new category for highly drug-resistant TB.

A 2011 report from India described 4 patients with tuberculosis (TB) for whom drug susceptibility testing (DST) of Mycobacterium tuberculosis cultures showed phenotypic resistance to all of 12 drugs examined (1). The authors of that report proposed the term: totally drug-resistant TB, abbreviated as TDR TB. To our knowledge, this was the fourth reported series of TB cases that showed resistance to all drugs tested, heralding the advent of TB strains resistant to all available anti-TB drugs (1–5).