Executive summary

Multidrug-resistant tuberculosis (MDR-TB), defined as TB caused by

organisms that are resistant to isoniazid and rifampicin, two first-line antiTB drugs, continues to threaten the progress made in controlling the disease. The emergence of extensively drug-resistant TB (XDR-TB), defined
as MDR-TB that is resistant as well to any one of the fluoroquinolones and
to at least one of three injectable second-line drugs (amikacin, capreomycin
or kanamycin), has heightened this threat. XDR-TB has been identified in
all regions of the world since 2006. Treatment outcomes are significantly
worse in XDR-TB patients than in MDR-TB patients. Outbreaks of XDRTB in populations with high prevalence of HIV have caused alarmingly high
mortality rates. The emergence of XDR-TB as a new threat to global public
health demands that health officials and health-care providers respond with
a coordinated strategy drawing on the Stop TB Strategy.1
Guidelines for the programmatic management of drug-resistant tuberculosis:
emergency update 2008 provides updated guidelines and recommendations
on how to manage drug-resistant TB (DR-TB) based on a rapid assessment of
the best available evidence by a group of experts. A fully revised second edition will be published in 2010, following WHO guidance on retrieval, synthesis and grading of evidence. Until that time, the emergency update serves
as interim guidance for TB control programmes and medical practitioners
on all aspects of the management of DR-TB, including XDR-TB. It contains
19 chapters based on the original 18 chapters from the first edition published
by the World Health Organization in 20062 plus an additional chapter on
patient-centered care.

The Stop TB Strategy launched by the World Health Organization in 2006 describes the recommended interventions that should be implemented to achieve the targets for global TB control
that have been established within the context of the Millennium Development Goals. See Raviglione MC, Uplekar MW. WHOs new Stop TB Strategy. Lancet, 2006, 367:952955.
2
Guidelines for the programmatic management of drug-resistant tuberculosis. Geneva, World Health
Organization, 2006 (WHO/HTM/TB/2006.361).
1

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GUIDELINES FOR THE PROGRAMMATIC MANAGEMENT OF DRUG-RESISTANT TUBERCULOSIS

The key changes for the emergency update 2008 are summarized below.
Chapter

Key recommendations
Key changes
(* indicates updated recommendation)

Chapter 1
Not applicable
Target audience is defined.
Background
Development of guidelines is
information on described.
drug-resistant
Stop TB Strategy is
tuberculosis summarized.


New data are provided from
the WHO/IUATLD Global
Project on Antituberculosis
Drug Resistance
Surveillance.


Updated information is
provided from a survey of the
network of supranational
reference laboratories to
determine the prevalence of
XDR-TB among strains sent
for drug susceptibility testing
(DST).
Definition of XDR-TB is
Chapter 4
Not applicable
Definitions: case introduced.
registration,
Concise instructions for
bacteriology and registration of new cases of
treatment XDR-TB are provided.
outcomes
Chapter 5
All patients at increased risk
Stronger emphasis is placed
Case-finding for MDR-TB should be screened on the recommendation that
strategies for drug resistance.* all patients at increased risk

Patients infected with HIV for MDR-TB should receive
should receive DST at the start DST, with the goal of
of anti-TB therapy to avoid universal access to DST for
mortality caused by all that need it.
unrecognized MDR-TB.*
The use of rapid DST in all

Rapid DST should be used for HIV-infected patients who are
the initial screening of MDR-TB smear-positive is highly
whenever possible. encouraged, and it is

Patients at increased risk for recommended that all
XDR-TB should receive DST of HIV-infected patients at
isoniazid, rifampicin, second- moderate to high risk be
line injectable agents and a screened for resistance in
fluoroquinolone.* order to avoid the high
mortality associated with
unrecognized MDR-TB.


An algorithm for the use of
rapid drug-resistance testing
is introduced.


The use of DST for second line drugs in case-finding for
XDR-TB is introduced, and
risk factors for XDR-TB are
described.
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Executive summary

Chapter

Key recommendations
Key changes
(* indicates updated recommendation)

Chapter 6
All patients with suspected
Definitions of common terms
Laboratory MDR-TB or XDR-TB need access used in laboratory issues are
aspects to laboratory services for provided at the start of the
adequate and timely diagnosis. chapter.

Laboratories should be tested New recommendations for
for proficiency and quality DST to second-line drugs are
assured externally to perform proposed based on recent
DST.* WHO policy guidance;

Laboratories should perform
References for regulations on
DST for the fluoroquinolones how to transport infectious
and second-line injectable specimens internationally are
agents where adequate capacity provided.
and expertise exists.*

DR-TB strains can be
transported safely across
international borders if inter national procedures and guide lines are followed.*

Laboratories must follow all
standardized protocols for
infection control and biosafety.

Quality control and quality
assurance should be in place
for microscopy, culture and DST.
Links with supranational
reference laboratories are
strongly encouraged.
Chapter 7
Design regimens with a
The five groups of anti-TB
Treatment consistent approach based on drugs are re-defined.
strategies for the hierarchy of the five groups Thioacetazone is placed in
MDR-TB of anti-TB drugs. Group 5. High-dose isoniazid

Promptly diagnose MDR-TB and and imipenem are added to
initiate appropriate therapy. Group 5.

Use at least four drugs with
Ciprofloxacin is removed as
either certain, or almost certain, an anti-TB agent because of
effectiveness. its weak efficacy compared

DST should generally be used to with other fluoroquinolones.
guide therapy; however, do not Strong caution is warranted
depend on DST of ethambutol for any programme that uses
or pyrazinamide in individual gatifloxacin given the rare but
regimen design, pyrazinamide, dangerous adverse effects of
Group 4 and 5 drugs. dysglycaemia associated

Do not use ciprofloxacin as an with this drug.
anti-TB agent in management A new review of DST of
of DR-TB.** second-line drugs has

Design a programme strategy resulted in strong caution
that takes into consideration against basing the design of
access to quality-assured DST, individual regimens on
rates of DR-TB, HIV prevalence, results of DST of ethambutol,
technical capacity and financial pyrazinamide, or Group 4 and
resources. 5 drugs.

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GUIDELINES FOR THE PROGRAMMATIC MANAGEMENT OF DRUG-RESISTANT TUBERCULOSIS

Chapter

Key recommendations
Key changes
(* indicates updated recommendation)

Chapter 7
Treat MDR-TB patients for
Table 7.2 is new and
(continued) 18 months past the date of summarizes programme
culture conversion. strategies accepted by the

Use adjunct therapies including Green Light Committee that
surgery and nutritional or social take into consideration
support. quality of DST, rates of

Treat XDR-TB aggressively DR-TB, technical capacity
whenever possible. and financial resources.

Treat adverse effects
The management of XDR-TB
immediately and adequately. is introduced.
Perform provider-initiated HIV
Stronger emphasis is placed
Chapter 10
HIV infection testing and counselling in all on performing DST of
and MDR-TB TB suspects.* HIV-infected individuals at

Use standard algorithms to the start of anti-TB therapy in
diagnose pulmonary and extra- areas of moderate or high
pulmonary TB. MDR-TB prevalence. This

Use mycobacterial cultures and, subject is also introduced in
where available, newer more Chapter 5 as a key change.
rapid methods of diagnosis.
Greater detail is provided on

Determine the extent (or the concomitant treatment of
prevalence) of anti-TB drug HIV and MDR-TB, including
resistance in patients with HIV. discussion of immune

Introduce antiretroviral therapy reconstitution inflammatory
(ART) promptly in MDR-TB or syndrome.
XDR-TB /HIV patients.
Table 10.3 provides a list of

Consider empirical therapy with potential overlapping and
second-line anti-TB drugs.* additive toxicities of ART and

Provide co-trimoxazole anti-TB therapy.
preventive therapy (CPT) as part
of a comprehensive package of
HIV care to patients with active
TB and HIV.*

Arrange treatment follow-up by
a specialized team.

Implement additional nutritional
and socioeconomic support.

Ensure effective infection
control.

Involve key stakeholders in
MDR-TB/HIV activities.

Monitor overlying toxicity with
ART and DR-TB therapy.

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Executive summary

Chapter

Key recommendations
Key changes
(* indicates updated recommendation)

Chapter 11
Standard monitoring should be New recommendations for
Initial evaluation, implemented for all patients on monitoring the response to
monitoring of MDR-TB treatment. treatment are described.
treatment and
Results both of sputum smear Laboratory monitoring for
management of and culture should be monitored patients receiving both ART
adverse effects monthly to evaluate treatment and MDR-TB therapy is added
response.* to Table 11.1.

Increased monitoring is
required in HIV cases and for
patients on ART.*

Health-care workers in MDR-TB
control programmes should be
familiar with the management
of common adverse effects of
MDR-TB therapy.

Ancillary drugs for the manage ment of adverse effects should
be available to the patient.
Chapter 12
Use disease education, DOT,
A section on communityTreatment socioeconomic support, based care and support is
delivery and emotional support, manage- added to this chapter. NTPs
adherence ment of adverse effects and are encouraged to add
monitoring systems to improve community-based care and
adherence to treatment. support into their national

National TB control programmes strategies and plans.
(NTPs) are encouraged to
incorporate community-based
care and support into their
national plans.*
Chapter 14
MDR-TB contact investigation
NTPs should consider
Management of should be given high priority, contact investigation of
contacts of and NTPs should consider XDR-TB as an emergency
MDR-TB patients contact investigation of XDR-TB situation.
as an emergency situation.*
Infection control, including
Infection control measures
Chapter 15
Drug resistance administrative and engineering are proposed, with special
and infection controls as well as personal attention to XDR-TB and the
control protection, should be made a high mortality of patients
high priority in all MDR-TB coinfected with HIV and
control programmes. DR-TB.

XDR-TB patients should be
XDR-TB patients should be
placed isolated following a placed in ward isolation until
patient-centred approach and no longer infectious.
WHO ethical and legal guidance MDR-TB patients should
until no longer infectious.* receive routine care outside
of normal HIV care settings.

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GUIDELINES FOR THE PROGRAMMATIC MANAGEMENT OF DRUG-RESISTANT TUBERCULOSIS

Chapter

Key recommendations
Key changes
(* indicates updated recommendation)

Chapter 18
A standardized method of
Chapter 18 has been
Category IV recording and reporting should rewritten to be simpler and
recording and be implemented in DR-TB more consistent with the
reporting system control programmes. DOTS recording and

DR-TB treatment cards should reporting system.
have an expanded section for The treatment card described
information on patients with in Chapter 18 has an
HIV.* expanded section for

The International Health information on patients with
Regulations (IHR2005) should HIV.
be followed.*
Box 18.1 provides additional
recording and reporting
components, which are
optional for programmes.


The International Health
Regulations 2005 should be
followed.
Chapter 19
Not applicable
Chapter 19 is the only
Managing DR-TB completely new chapter in
through patient- this revision.
centered care

Any patient in whom MDR-TB or

XDR-TB is suspected or

diagnosed should be provided

with high-quality patient
centered care, as outlined in

both the International

Standards for Tuberculosis

Care, the Patients Charter for

Tuberculosis Care and in the

WHO Good Practice in

Legislation and Regulations for

TB Control.

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