Webinar

Scientific highlights of 47th Union World Conference on Lung Health

Tuesday 30 August 2016

Toward MDR-TB control in the World.

Increasing Detection and Cure
Prof. Jose A. Caminero, MD
Multi-Drug-Resistant Unit Coordinator
International Union against Tuberculosis and Lung Disease (The Union)

Mycobacterium tuberculosis Resistance

Definitions
Multidrug-resistance Tuberculosis (MDR-TB)
Mycobacterium tuberculosis resistant to, at least, Isoniazide and
Rifampicin, the two best anti-TB drugs
- 500.000 new cases yearly and 200.000 deaths

Extensively-drug-resistance TB (XDR-TB)
MDR-TB plus resistance to any Fluoroquinolone and, at least, one
second line drug injectable (kanamycin, amikacin and capreomycin),
the two best second line drugs available
- 50.000 new cases yearly and 30.000 deaths

MDR-TB remains a public health

crisis

Case Detection: 25%

Cured Rate: 50%

The 90-90-90 targets proposed for

the Global Plan to End TB:

1. Finding at least 90% of all TB cases in the

population
and put as many as possible
of these on effective treatment.
2.Making a special effort to reach at
least 90% of the most
vulnerable,
underserved or at risk populations (Key
populations for TB) in the countries
through
screening and active case finding

3.Reaching at least 90% treatment success

DR-TB control

Therefore, to Achieve a Control of the DR-TB Epidemic,

it is very urgent to Increase notably the Rate of
Detection of TB cases (susceptible and DR-TB) and the
Rate of Cured cases of DR-TB

How can be Increased the TB and MDR-TB

Detection ?
1. Rapid (Molecular) and very sensitive Drug
Susceptibility Test for all the patients with
Suspect of TB GeneXpert Ultra or Similar
2. To Improve the Health Coverage of all the
Patients To Strength the Health System
(totally Free)

Support of GeneXpert to the Detection of

Susceptible and Resistant TB

- Support to the Detection of

Susceptible TB 70% of Smear
Negative TB
- Support to the Detection of TB
with RIF Resistance Amplifition
rpoB, responsible of 95% of
the resistance to RIF

- Moreover, in the field, more than 95%

Coming soon
Xpert for HIV-1 Viral Load
(< 2houres, until 400 resulta/day)
GeneXpert Omni (point of care, smalles,
mobile, low consume, aso for HPV, HCV,
ebola. )
Xpert MTB/Rif Ultra (more sensitive,
to liquid culture)
Xpert XDR (in a bear future)

similar

GeneXpert Omni

Available in 2016
Price $2,895

Cepheid C360
(Remote Expert)
RemoteXpert
for Robust Data Management
Real-time communications
Automated remote data
collection
Accelerates clinical
decision-making and patient
management
System-wide data surveillance

11

Cepheid. Confidential

Xpert MTB RIF Ultra

Key Product Specifications
Xpert MTB RIF Ultra
Specification
Time to result
Hands on time
Sample type
Targets
Analytical Performance: Inclusivity
(Reactivity)
Clinical Performance: Sensitivity (MTB)
Clinical Performance:
Sensitivity (Rif-resistance)
Clinical Performance: Specificity (MTB)
Clinical Performance: Specificity (Rifresistance)
New Hardware

Target
85 minutes following 15 minute
incubation
<2 mins
Sputum, induced sputum, sediment
MTBC (IS6110, IS1081), RIF (rpoB)
MTB Complex
98% (Smear+, Culture+)
90% (Smear-, Culture+)
95%
98%
98%
Not needed, users can use existing
instrumentation

TUBERCULOSI S DI AGNOSTI CS

MOLECULAR LINE-PROBE ASSAY

FOR THE DETECTION OF RESISTANCE TO
SECOND-LINE ANTI-TB DRUGS (SL-LPA)
BACKGROUND

Multidrug-resistant tuberculosis (MDR-TB) is a

public health crisis and a global health security
risk carrying grave consequences for those
affected.
An estimated 480 000 people developed MDRTB in 2014 and 190 000 people died as a result
of it.
Photo credit: FIND
Early detection of people with MDR-TB is one of
the major bottlenecks in tackling this epidemic.
BENEFITSOFTHESL-LPA
Of the 480 000 MDR-TB cases estimated to have
The SL-LPA produces results in just 24-48 hours, a
occurred in 2014, only about a quarter
vast improvement over the 3 months or longer
123 000 were detected and reported to
currently required.
national authorities.
It allows quick triage of confirmed rifampicinIn
May
2016,
WHO
issued
new
resistant or MDR-TB patients into either the shorter
recommendations on the use of a rapid
MDR-TB regimen or the conventional longer
diagnostic test a line probe assay to detect
regimen.
resistance to second-line anti-TB drugs (SL-LPA).
Excluding second-line drug resistance a critical
WHO recommends this rapid diagnostic test for
prerequisite for identifying patients who can be
identifying those MDR- or rifampicin-resistant
placed on the shorter MDR-TB regimen.
TB patients
who can be placed
the shorter
http://
www.who.int/
tb/on
areas-of-work/laboratory/policy_statements
Detection of any second-line resistance by the SLMDR-TB regimen. The results of this test will
LPA means that MDR-TB patients should not be
also be critical in placing patients on targeted
enrolled on the shorter regimen as this could
POL
ICYREC
OMMEND
TION
STABLIS
HINGand
SL-L
PA
conventional
MDR-TB
regimensA
with
improved
jeopardise their E
treatment
outcome
fuel
theAT CO

WHO

RECOMMENDATIONS
ON THE USE OF THE SL-LPA

WHO

rifampicin-resistant
or MDR-TB patients, including
W
HO
RECOMMENDATIONS
RECOMMENDAT
IONSof the smear
adults and children
(irrespective
ON THE USE OF THE SL-LPA
ON THE USE OF THE SL-LPA
status).
S
For second-line injectable results, resistance
conferring mutations detected by SL-LPA are highly
A AT COUNTRYLEVEL
correlated
with
culture-based
phenotypic
resistance.
For fluoroquinolones, resistance confirming
mutations detected by SL-LPA are better correlated
with culture-based phenotypic resistance to
ofloxacin/levofloxacin
in
comparison
to
moxifloxacin; inclusion of moxifloxacin in a
rifampicin-resistant or MDR-TB regimen is
therefore best guided by phenotypic testing.
http:/ /www.who.int/tb/areas-of-work/ laboratory/ policy_statements

POLICYRECOMMENDATION

ESTABLISHING SL-LPA AT COUNTRYLEVEL

WHO recommends the use of the SL-LPA for patients

with confirmed rifampicin-resistant TB or MDR-TB as
the initial test to detect resistance to fluoroquinolones
and the second-line injectable drugs, instead of
phenotypic culture-based drug-susceptibility testing
(DST).

CONDITIONS

These recommendations apply to the use of SL-LPA

for the direct testing of sputum specimens as well
as indirect testing on culture isolates from
rifampicin-resistant or MDR-TB patients, including
adults and children (irrespective of the smear
tingstatus).
LPA capacity can
For second-line injectable results, resistance
e SL-LPA
asmutations
the laboratory
conferring
detected by SL-LPA are highly
correlated
as for first-linewith
LPA.culture-based phenotypic
resistance.
useFor atfluoroquinolones,
national/central
resistance confirming
detected by SL-LPA are better correlated
s ormutations
those
with
proven
with culture-based phenotypic resistance to
ofloxacin/levofloxacin
in
comparison
to
molecular
testing. Expansion
moxifloxacin; inclusion of moxifloxacin in a
ed laboratories
be regimen is
rifampicin-resistant could
or MDR-TB
therefore
best
guided
by
phenotypic
on availability of suitable testing.
Theses recommendations do not eliminate the
cture,need for
specially
trained
phenotypic DST
to confirm resistance to
drugs and to monitor the emergence of
uate other
quality
assurance
of
additional drug resistance during treatment.

appropriate
laboratory
uipment must be available,
y biosafety precautions and
ontamination:
specimen
re and manipulation of
ntainment laboratories with
safety cabinets. Laboratory
re at least three separate
for DNA extraction, preres, and amplification and
cedures. Restricted access

results
pattern

Countries with existing LPA capacity can

immediately adopt the SL-LPA as the laboratory
methods are the same as for first-line LPA.
LPA is suitable for use at national/central
reference laboratories or those with proven
capability to conduct molecular testing. Expansion
to more decentralised laboratories could be
considered depending on availability of suitable
laboratory infrastructure, specially trained
personnel and adequate quality assurance of
testing.
Adequate
and
appropriate
laboratory
infrastructure and equipment must be available,
including the necessary biosafety precautions and
prevention
of
contamination:
specimen
processing for culture and manipulation of
cultures require TB containment laboratories with
appropriate biological safety cabinets. Laboratory
facilities for LPA require at least three separate
rooms - one each for DNA extraction, preamplification procedures, and amplification and
post-amplification procedures. Restricted access
to molecular facilities, unidirectional work flow,
and stringent cleaning protocols must be
established to avoid contamination.
Appropriate laboratory staff should be trained to
conduct LPA procedures. Supervision of staff by a
senior individual with adequate training and
experience in molecular assays is strongly
recommended. A programme for external quality
assessment of involved laboratories should be
developed as a priority. Mechanisms for rapid
reporting of LPA results to clinicians must be
established to provide patients with the benefit of
an early diagnosis.
By 2014 approximately 400 LPA laboratories had
been established in low and middle-income
countries, as reported to WHO.

http:/ / www.who.int/tb/areas-of-work/laboratory/policy_statements

POLICYRECOMMENDATION

ESTABLISHING SL-LPA AT COUNTRYLEVEL

WHO recommends the use of the SL-LPA for patients

with confirmed rifampicin-resistant TB or MDR-TB as
the initial test to detect resistance to fluoroquinolones
and the second-line injectable drugs, instead of
phenotypic culture-based drug-susceptibility testing
(DST).

CONDITIONS

These recommendations apply to the use of SL-LPA

for the direct testing of sputum specimens as well
as indirect testing on culture isolates from
rifampicin-resistant or MDR-TB patients, including
adults and children (irrespective of the smear
status).
For second-line injectable results, resistance
conferring mutations detected by SL-LPA are highly
correlated
with
culture-based
phenotypic
resistance.
For fluoroquinolones, resistance confirming
mutations detected by SL-LPA are better correlated
with culture-based phenotypic resistance to
ofloxacin/levofloxacin
in
comparison
to
moxifloxacin; inclusion of moxifloxacin in a
rifampicin-resistant or MDR-TB regimen is
therefore best guided by phenotypic testing.
Theses recommendations do not eliminate the
need for phenotypic DST to confirm resistance to
other drugs and to monitor the emergence of
additional drug resistance during treatment.

Assay
results
pattern

Countries with existing LPA capacity can

immediately adopt the SL-LPA as the laboratory
methods are the same as for first-line LPA.
LPA is suitable for use at national/central
reference laboratories or those with proven
capability to conduct molecular testing. Expansion
to more decentralised laboratories could be
considered depending on availability of suitable
laboratory infrastructure, specially trained
personnel and adequate quality assurance of
testing.
Adequate
and
appropriate
laboratory
infrastructure and equipment must be available,
including the necessary biosafety precautions and
prevention
of
contamination:
specimen
processing for culture and manipulation of
cultures require TB containment laboratories with
appropriate biological safety cabinets. Laboratory
facilities for LPA require at least three separate
rooms - one each for DNA extraction, preamplification procedures, and amplification and
post-amplification procedures. Restricted access
to molecular facilities, unidirectional work flow,
and stringent cleaning protocols must be
established to avoid contamination.
Appropriate laboratory staff should be trained to
conduct LPA procedures. Supervision of staff by a
senior individual with adequate training and
experience in molecular assays is strongly
recommended. A programme for external quality
assessment of involved laboratories should be
developed as a priority. Mechanisms for rapid
reporting of LPA results to clinicians must be
established to provide patients with the benefit of
an early diagnosis.
By 2014 approximately 400 LPA laboratories had
been established in low and middle-income
countries, as reported to WHO.

WHO

Patients detected with XDR-TB by the SL-LPA should

WHO
RECOMMENDATIONS
also not be enrolled
on the shorter
regimen but
RECOMMENDAT
IONS
ON THE USE OF THE SL-LPA
require carefully
designed
individual regimens to
ON THE
USE OF THE SL-LPA
TBDRsl is a
optimise their chances of success.
Ses genetic
making them
COSTS
d injectable
FIND has negotiated a preferential price of Euro
A AT COUNTRYLEVEL
ting LPA capacity can
7.50 (approximately USD10) for the MTBDRsl strips
e SL-LPA as the
laboratory
only
WHOas for first-line LPA.
use at national/central
in 138 countries (http://www.finddx.org/pricing/);
detection
of
s or those with proven
molecular testing. Expansion
however, doing the test requires other laboratory
tients
as well
ed laboratories could be
on availability of suitable
consumables and supplies which may push the cost
ay
tospecially
rule trained
out
cture,
uate quality assurance of
up to between USD20 and USD30.
appropriate
laboratory
uipment must be available,
The cost of the equipment to perform the test
y biosafety precautions and
ontamination:
specimen
.who.int/tb
ranges between approximately USD8,000 and
re and manipulation of
ntainment
16 laboratories with
USD40,000 depending on the size of the equipment
safety cabinets. Laboratory
re at least three separate
and whether results are read automatically or not.
for DNA extraction, prehttp:/ /www.who.int/tb/areas-of-work/ laboratory/ policy_statements

POLICYRECOMMENDATION

ESTABLISHING SL-LPA AT COUNTRYLEVEL

WHO recommends the use of the SL-LPA for patients

with confirmed rifampicin-resistant TB or MDR-TB as
the initial test to detect resistance to fluoroquinolones
and the second-line injectable drugs, instead of
phenotypic culture-based drug-susceptibility testing
(DST).

CONDITIONS

These recommendations apply to the use of SL-LPA

for the direct testing of sputum specimens as well
as indirect testing on culture isolates from
rifampicin-resistant or MDR-TB patients, including
adults and children (irrespective of the smear
status).
For second-line injectable results, resistance
conferring mutations detected by SL-LPA are highly
correlated with
culture-based
phenotypic
resistance.
For fluoroquinolones, resistance confirming
mutations detected by SL-LPA are better correlated
with culture-based phenotypic resistance to
ofloxacin/levofloxacin
in
comparison
to
moxifloxacin; inclusion of moxifloxacin in a
rifampicin-resistant or MDR-TB regimen is
therefore best guided by phenotypic testing.
Theses recommendations do not eliminate the
need for phenotypic DST to confirm resistance to
other drugs and to monitor the emergence of
additional drug resistance during treatment.

res, and amplification and

cedures. Restricted access

results
pattern

Countries with existing LPA capacity can

immediately adopt the SL-LPA as the laboratory
methods are the same as for first-line LPA.
LPA is suitable for use at national/central
reference laboratories or those with proven
capability to conduct molecular testing. Expansion
to more decentralised laboratories could be
considered depending on availability of suitable
laboratory infrastructure, specially trained
personnel and adequate quality assurance of
testing.
Adequate
and
appropriate
laboratory
infrastructure and equipment must be available,
including the necessary biosafety precautions and
prevention
of
contamination:
specimen
processing for culture and manipulation of
cultures require TB containment laboratories with
appropriate biological safety cabinets. Laboratory
facilities for LPA require at least three separate
rooms - one each for DNA extraction, preamplification procedures, and amplification and
post-amplification procedures. Restricted access
to molecular facilities, unidirectional work flow,
and stringent cleaning protocols must be
established to avoid contamination.
Appropriate laboratory staff should be trained to
conduct LPA procedures. Supervision of staff by a
senior individual with adequate training and
experience in molecular assays is strongly
recommended. A programme for external quality
assessment of involved laboratories should be
developed as a priority. Mechanisms for rapid
reporting of LPA results to clinicians must be
established to provide patients with the benefit of
an early diagnosis.
By 2014 approximately 400 LPA laboratories had
been established in low and middle-income
countries, as reported to WHO.

http:/ / www.who.int/tb/areas-of-work/laboratory/policy_statements

POLICYRECOMMENDATION

ESTABLISHING SL-LPA AT COUNTRYLEVEL

WHO recommends the use of the SL-LPA for patients

with confirmed rifampicin-resistant TB or MDR-TB as
the initial test to detect resistance to fluoroquinolones
and the second-line injectable drugs, instead of
phenotypic culture-based drug-susceptibility testing
(DST).

CONDITIONS

These recommendations apply to the use of SL-LPA

for the direct testing of sputum specimens as well
as indirect testing on culture isolates from
rifampicin-resistant or MDR-TB patients, including
adults and children (irrespective of the smear
status).
For second-line injectable results, resistance
conferring mutations detected by SL-LPA are highly
correlated
with
culture-based
phenotypic
resistance.
For fluoroquinolones, resistance confirming
mutations detected by SL-LPA are better correlated
with culture-based phenotypic resistance to
ofloxacin/levofloxacin
in
comparison
to
moxifloxacin; inclusion of moxifloxacin in a
rifampicin-resistant or MDR-TB regimen is
therefore best guided by phenotypic testing.
Theses recommendations do not eliminate the
need for phenotypic DST to confirm resistance to
other drugs and to monitor the emergence of
additional drug resistance during treatment.

Assay
results
pattern

Countries with existing LPA capacity can

immediately adopt the SL-LPA as the laboratory
methods are the same as for first-line LPA.
LPA is suitable for use at national/central
reference laboratories or those with proven
capability to conduct molecular testing. Expansion
to more decentralised laboratories could be
considered depending on availability of suitable
laboratory infrastructure, specially trained
personnel and adequate quality assurance of
testing.
Adequate
and
appropriate
laboratory
infrastructure and equipment must be available,
including the necessary biosafety precautions and
prevention
of
contamination:
specimen
processing for culture and manipulation of
cultures require TB containment laboratories with
appropriate biological safety cabinets. Laboratory
facilities for LPA require at least three separate
rooms - one each for DNA extraction, preamplification procedures, and amplification and
post-amplification procedures. Restricted access
to molecular facilities, unidirectional work flow,
and stringent cleaning protocols must be
established to avoid contamination.
Appropriate laboratory staff should be trained to
conduct LPA procedures. Supervision of staff by a
senior individual with adequate training and
experience in molecular assays is strongly
recommended. A programme for external quality
assessment of involved laboratories should be
developed as a priority. Mechanisms for rapid
reporting of LPA results to clinicians must be
established to provide patients with the benefit of
an early diagnosis.
By 2014 approximately 400 LPA laboratories had
been established in low and middle-income
countries, as reported to WHO.

How can be Increased the Successful

Outcome in the MDR-TB Treatment ?

1. Shorter MDR-TB Regimens and better

tolerated
2. Possibility to Incorporate New Drugs:
Linezolid, Bedaquiline, Delamanid,
Pretomanid, etc

To Cure > 90% MDR-TB

Cases

With the current MDR-TB

regimens the highest
Successful Outcome is
around 50-60%

Outcomes of MDR-TB treatment

MDR-TB cohorts 2007-2012, global

Outcomes of XDR-TB treatment

XDR-TB cohorts 2012, by WHO Region*

*number of cases observed shown next to the

bars

Am J Respir Crit Care Med Vol 182. pp 684692, 2010

- Bangladesh: 427 MDR-TB (1997-2007) not receiving previously SLD

- 206 (4 Kn-Pth-H-Gx-Cfz-E-Z / 5 Gx-Cfz-E-Z) CURE 87.9%
(relapse-free) (95% CI, 82.791.6)
- Major adverse drug reactions were infrequent and manageable.
- Compared with the 221 patients treated with regimens based on
ofloxacin and commonly prothionamide throughout, the
hazard ratio of any adverse outcome was 0.39 (95%
confidence
interval, 0.260.59).

TB in
on on
under

enefit
dwide;
sening
riately

mized
n the
ective

/tb

which is tolerable have been ongoing for several

resistant-TB,
regardless
of patient age or HIV status
years through
various studies.
FEATURESOFTHE
Recently,
a
standardized
treatment
regimen
Monitoring for effectiveness, harms and relapse will
lasting less than 12 months has been used in a
SHORTERMDR-TB
be needed.
Patient-centred
and
social support
number of
countries (see map).care
It has
shown
Standardized shorter
results
in selected
patients
will bepromising
essential
to
enableMDR-TB
patient
adherence drugs and a treatment
Based on data from these studies, WHO updated
Indicated conditionall
Programmatic
is feasible
in most
its treatmentuse
guidelines
for drug-resistant
TBsettings
in
resistant-TB, regardles
May 2016 and included a recommendation on
Monitoring for effectiv
worldwide
the use of the shorter MDR-TB regimen under
be needed. Patient-ce
Lowered
costs
and
reduced
patient
loss
expected
specific conditions.
will be essential to en
nd
This new
recommendation
is expected
to benefit
Programmatic use is fe
Exclusion
criteria:
2 line
drug resistance,
the majority of MDR-TB patients worldwide;
worldwide
extrapulmonary
disease
and
pregnancy.
however, there are serious risks for worsening
Lowered costs and red
resistance if the regimen is used inappropriately
Exclusion criteria: 2nd l
Countries usingthe shorter MDR-TBregimen
BACKGROUND (e.g. in XDR-TB patients).
extrapulmonary disea
(excludingclinical trial sites)
Multidrug-resistant tuberculosis
(MDR-TB) is ongoing
a
WHO encourages
and future randomized
public health crisis and a global health security
controlled clinical trials to strengthen the
REGIMENCOMPO
risk carrying grave consequences for those
evidence base for shorter
and more effective
high-dose
affected.
4-6 Km-Mfx-Pto-Cfz-Z-H
regimens.
An estimated 480 000 people
developed MDR-TB

THE SHORTER
MDR-TB REGIMEN
REGIMENCOMPOSITION
4-6 Km-Mfx-Pto-Cfz-Z-H

-E / 5 Mfx-Cfz-Z-E

Km=Kanamycin; Mfx=Moxifloxacin;
Km=Kanamycin; Mfx=M
Pto=Prothionamide; Cfz
Pto=Prothionamide; Cfz=Clofazimine;
Z=Pyrazinamide; Hhigh-do
Z=Pyrazinamide; H
=high-dose Isoniazid;
E=Ethambutol

in 2014 and 190 000 people died as a result of it.

MDR-TB cannot be treated with the standard 6For
more information
month course of first-line
medication
which is please visit: www.who.int/tb
effective in most TB patients. Patients with
World Health Organization May2016
rifampicin-resistant or MDR-TB are treated with
a
high-dose
different combination of second-line drugs,

Shorter MDR-TB regimen (2)

Treatment success versus failure/relapse/death
Resistance pattern
All cases regardless of
pyrazinamide and
fluoroquinolone
susceptibility
Pyrazinamide resistant;
fluoroquinolone
resistant
Pyrazinamide resistant;
fluoroquinolone
susceptible
Pyrazinamide
susceptible;
fluoroquinolone
resistant
Pyrazinamide

Shorter MDR-TB regimen

Conventional MDR-TB
regimen

% (95% CI)

% (95% CI)

1008/1116

90.3% (87.8%
92.4%)

4033/5850

78.3% (71.2%
84%)

19/28

67.9% (47.6%
84.1%)

81/137

59.1% (50.6%
67.1%)

90/100

88.8% (47.3%
98.6%)

840/1075

81.4% (71.6%
88.4%)

12/15

80.0% (50.0%
94.1%)

72/120

64.4% (49.6%
76.9%)

121/125

96.8% (77.3%

890/1119

83.5% (75.7%

How can be Increased the Successful

Outcome in the MDR-TB Treatment ?

1. Shorter MDR-TB Regimens and better

tolerated
2. Possibility to Incorporate New Drugs:
Linezolid, Bedaquiline, Delamanid,
Pretomanid, etc

New Drugs for the Treatment of

MDR-TB

Of the 110,000 persons placed

on MDR-TB treatment in 2014,
30-50% (33,000-55,000) would
benefit from Bdq or Dlm

Desirable Characteristics of Drugs.

LINEZOLID

1. Bactericidal Moderate Bactericidal Activity

2. Sterilization the higher rate of culture
negative at the end of the 2-6 month is a
Surrogate of the possible Sterilizing activity or
Linezolid

3. Prevention of Resistance in combined drugs Good,

but very limited data

4. Minimal Toxicity Controversial, but manageable reducing dose

Desirable Characteristics of Drugs.

BEDAQUILINE

1. Bactericidal Significant Bactericidal Activity of

400 mg Bq from day 4 onward

2. Sterilization the higher rate of culture negative

at the end of the 2 month is a Surrogate of the
possible Sterilizing activity or Bedaquiline

3. Prevention of Resistance in combined drugs Good, but

very limited data

4. Minimal Toxicity Controversial, , just moderate problem with QTc,

but easily manageable

Desirable Characteristics of Drugs.

DELAMANID

1. Bactericidal Significant Bactericidal Activity

working in micolic acid of cellular wall

2. Sterilization Good Active against Latent

Bacilli (Anaerobic static culture model and
structure related to metronidazol

3. Prevention of Resistance in combined drugs Very

probably good, but very limited data

4. Minimal Toxicity Good, just moderate problem with QTc, easily

manageable

Conclusions. Important Advances

MDR-TB
1. Diagnosis:
1.

2.

GeneXpert
1.

Widely Implementation in many high burden TB countries

2.

Coming soon. Omni (portable) and Ultra (higher sensitivity

LPA for SLD Important support to identify XDR-TB and adequate treatment

2. Treatment
1.

Shorter MDR-TB regimens (9-12 months) Increasing implementation in the

world

2.

Role of New Drugs: Linezolid, Bedaquline, Delamanid