Historia De Un Amigo

Introduction

In December, 2011, four cases of tuberculosis that were

resistant to all fi rst-line and second-line drugs were

described in India,

1

following similar reports from Italy

in 2007, and Iran in 2009.

2,3

Soon after the Indian cases

were reported, this strain of tuberculosis, labelled totally

drug-resistant tuberculosis, began to garner widespread

international media attention.

In response to the discovery in India and other reports

of patients infected with totally drug-resistant tuberculosis strains, the WHO Stop TB Department convened

a meeting in March, 2012, to discuss the notion of totally

drug-resistant tuberculosis and the actual existence of

such strains. This expert group concluded that because

of inadequate drug susceptibility testing (DST) for some

second-line tuberculosis drugs—a crucial requirement

for classifi cation of tuberculosis strains as drugresistant—terms like totally drug-resistant should not

currently be used in relation to tuberculosis.

4

Instead,

they proposed that the drug-resistant tuberculosis

classification be restricted to the existing multidrugresistant and extensively drug-resistant tuberculosis

terms, for which DST is more reliable.

The terms multidrug-resistant and extensively drugresistant signify that the disease is resistant to some of

the most frequently used antituberculosis drugs;

however, through advances in drug discovery, the

standard of tuberculosis care might soon change. When

much needed new drugs reach the market, some

important questions will arise about the future of drugresistant tuberculosis classifi cation: should the terms

multidrug-resistant and extensively drug-resistant be

redefined to refl ect resistance to the new regimens? Or

should this terminology be abandoned and replaced by

a more nuanced classifi cation system? In this Personal

View, we discuss the evolution of drug-resistant tuberculosis classification, briefly present new tuberculosis

drugs and regimens in the pipeline, and propose three

possible approaches to classifi cation of resistant cases

in the coming era as new drugs reach the market.

Lastly, we emphasise the importance of reliable DST

in the development of a new, clinically relevant

classification system.

The history of drug-resistant tuberculosis

terminology

The development of bacterial resistance was identified

soon after initial antibiotic treatments for tuberculosis

were introduced in the 1940s.5

Although regimens

containing isoniazid and rifampicin were developed

throughout the next 30 years, the term multidrugresistant tuberculosis, which denotes resistance to both

of these drugs, did not gain widespread use until the

early 1990s.

6

Soon afterwards, increasingly resistant

strains of tuberculosis were reported, and in 2006, WHO

introduced the defi nition of extensively drug-resistant

tuberculosis—an upgrade from multidrug-resistant

tuberculosis—defined as strains resistant not only to

isoniazid and rifampicin, but also to any fl uoroquinolone

and one of the three second-line injectable antituberculosis drugs (kanamycin, amikacin, or capreomycin).

7,8

This 2006 defi nition of extensively drug-resistant

tuberculosis was a revision of a previous classification,

set in 2005, that defi ned extensively drug-resistant

tuber culosis as a subset of multidrug-resistant tuberculosis with additional resistance to any three secondline antituberculosis drugs.

9,10

The revised, more precise

definition was deemed necessary by a task force

convened by WHO because susceptibility testing for

many tuber culosis drugs (particularly ethambutol,

pyrazinamide, the thioamides, the serine derivatives,

and para-aminosalicylic acid) was not straightforward,

11–13

and the reproducibility of DST for these drugs only

ranged from 50–80%. By contrast, DST methods for

drugs covered by the new defi nition were considered to

be more than 90% reproducible. Additionally, the

revised defi nition supported more accurate case

detection and surveillance in the short term, since DST

was not available for at least three second-line drugs.

This partly shows the complex reasoning behind

Lancet Infect Dis2013;

13: 373–76

Published Online

March 13, 2013

http://dx.doi.org/10.1016/

S1473-3099(12)70318-3

Division of Infectious Diseases,

Mount Sinai Hospital, New

York, NY, USA(T Sullivan MD);

and The Earth Institute,

Columbia University, New

York, NY, USA(Y Ben Amor PhD)

Correspondence to:

Dr Yanis Ben Amor, The Earth

Institute, Columbia University,

475 Riverside Drive, Suite 520,

New York, NY 10115, USA

yba2101@columbia.edu

374 www.thelancet.com/infection Vol 13 April 2013

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