This presentation describes how many developing nations are failing to transcribe WHO guidelines while prescribing Anti-Tb medications. A failure which is observed as MDR.

1. Multi Drug Resistance Assay:
A New Dimension for Host
Directed Therapy
PRESENTED BY:
CYRIL JOSE
KESRIN AMRA
OP 1

2. Introduction
 Availabilility of many anti-TB drugs to treat
people with tuberculosis (TB), but
resistance to these drugs is a growing
problem.
 People with drug-resistant TB require
“second-line” TB drugs that, compared
with “first-line” TB drugs used to treat
drug-susceptible TB, cause more side
effects and must be taken for longer.
 A rapid and accurate test could identify
people with drug-resistant TB, likely
improve patient care, and reduce the
spread of drug-resistant TB.

3. Types of resistance
Rifampicin
resistance
• TB bacteria do
not respond to
rifampicin
therapy
• Require second
line treatment
Multi drug
resistance
• Resistant to
atleast
rifampicin and
isoniazid
• Need second
line of treatment
Extensively drug
resistant
• Resistant to first
and second line
drugs
• Resistant to
fluoroquinolones

4. Conventional therapy
1st line
Isoniazid
Rifampicin
Pyrazinamide
Ethambutol
2 nd line
Para amino
salicylic acid
Streptomycin
Ethionamide
Cycloserine

6. Selection of individualized MDR-TB
regimens
 Based on the patient's history of past drug use
and on DST of isoniazid, rifampicin, the second-line
injectable agents and a fluoroquinolone. Although
resistance can develop in less than 1 month, if a
patient has used a drug for more than 1 month with
persistently positive smears or cultures, the strain
should – as a general rule – be considered as
“probably resistant” to that drug, even if DST results
indicate that it is susceptible.
 Another important limitation is the turnaround time
for DST results…so the WHO recommends much
rapid and simpler Genotypic MDR assays.

7. Different levels of MDR observed are
 Cross resistance
 Different minimum inhibitory
concentration
 Resistance to one or more drug of a
particular group
MDR assays are conducted on
Sputum specimen
Culture isolates

8. Assay Methods
• Line Probe assay
• Loop mediated isothermal
amplification
• Oligonucleotide microarray
• Xpert MTB/RIF
Molecular methods
• Fluorescent light emitting diode
• Colorimetric assay
• MDR XDR Color testNon molecular
methods

9. WHO recommended MDR assays
Conventional phenotypic DST
 to evaluate emergence of additonal drug resistance.
 to confirm resistance to other drugs.
Genotype MTBDR assay
WHO recommends SL-LPA for patients with confirmed RR-TB or MDR TB as the
initial test to detect resistance to FQs & 2nd line injectable drugs.
Among patients prescribed conventional MDR-TB, MDR assays can help to decide
who would benefit from new medicines to strengthen the regimen
WHO recommended MDR-TB regimen
Treated with different combination of 2nd line drugs.
Short term MDR-TB regimen.
In patients with rifampicin-resistant or multidrug-resistant TB who have not been
previously treated with second-line drugs and in whom resistance to
fluoroquinolones and second-line injectable agents has been excluded or is
considered highly unlikely, a shorter MDR-TB regimen of 9-12 months may be used
instead of a conventional regimen (conditional recommendation, very low certainty
in the evidence)

10. Good quality
drugs
Political and
administrative
commitment
Good quality
diagnosis
Directly
observed
treatment
Systemic
monitoring
and
accountability
Elements
of DOTS

11. Problems associated with the DOTS strategy (observed in India)
Resistance to DOTS therapy reported
DOTS plus strategy yet to be launched to tackle the MDR-TB issue which
comprises of 2nd line drug.
DOTS strategy in India

12. Personalisation of medicines
Why do we generalise TB like most other diseases...???
Especially since MDR cases are advancing in current scenario...why do we
still follow the same treatment regimen in almost the entire population..???
Don’t you feel there is a need for MDR assays before prescribing an anti-
TB drugs..???
Why do we have to wait to ascertain the ineffectiveness of the regimen till
the patient is not responding to the treatment pattern...??
As a budding pharmacist...many of you all like me would be concerned to
protect the molecular integrity of the newly launched anti-TB drugs..!!!Due
to their haphzard prescription...!!!......Aren’t we...???

13. Challenges
Ahead...!!!!
India has 121 labs
performing XPERT
MTB/RIF.
Only 0.2% TB cases
reportedly undergoes DST
testing in these labs...!!!!
Will the newly launched
molecules bedaquilline and
Delamanid face the same
fate as streptomycin..????

14. Risks Strategy
prior treatment for tuberculosis as a risk
factor for drug resistant tuberculosis
Simultaneous MDR Genotypic assays
alongwith TB diagnosis for detecting
presence of any resistance to first line
drugs.
inadequate treatment in both the public
health system and the hospital system
because they have disease that is
resistant to isoniazid or rifampin (or
both) but are still given these first line
TB drugs as part of standard treatment)
• selection of treatment regimens on
the basis of testing for initial drug
resistance
• enhance the continuity of treatment
after patients leave the hospitals
Emergence of drug resistance by strains
due to genetic mutations allow them to
survive even in the presence of these
agents.
using several anti-TB agents
concurrently
Use of a shorter MDR-TB treatment
regimen