Multi drug resistance Tuberculosis, Diagnostic techniques, Treatment etc

1. MDR TB

2.  Introduction
 Anti tuberculosis drug
 Various definitions
 MDR TB
 Various diagnostic modality
 Treatment
 prevention

3.  Tuberculosis (TB) is an infectious disease caused predominantly
by Mycobacterium tuberculosis and among the leading causes of
mortality in India.
 India accounts for 1/5 of the global TB burden. Pulmonary
tuberculosis is the most common site for tuberculosis but it also
affects other sites, which is called extra pulmonary tuberculosis.

4. Drugs used :
First line drugs :
- Isoniazid- Isoniazid is a prodrug and must be activated by a bacterial catalase-peroxidase
enzyme that in mycobacterium tuberculosis is called KatG.KatG couples the isonicotinic acyl with NADH to
form isonicotinic acyl-NADH complex. This complex binds tightly to theenoyl-acyl carrier protein reductase
known as InhA, thereby blocking the natural enoyl-AcpM substrate and the action of fatty acid synthase. This
process inhibits the synthesis of mycolic acid, required for the mycobacterial cell wall.
- Rifampicin -Rifampicin inhibits bacterial DNA-dependent RNA synthesis by inhibiting
bacterial DNA-dependent RNA polymerase.
- Pyrazinamide
- Ethambutol
- Streptomycin

5. A drug may be classed as second-line instead of first-line for one of three possible
reasons:
 It may be less effective than the first-line drugs
 It may have toxic side-effects
 It may be effective, but unavailable in many developing countries
 Aminoglycosides = amikacin (AMK), kanamycin (KM)
 Polypeptides = capreomycin, viomycin, enviomycin
 Fluoroquinolones = ciprofloxacin (CIP), levofloxacin, moxifloxacin (MXF)
 Thioamides = ethionamide, prothionamide
 Terizidone

6. Third line
Third-line drugs include drugs that may be useful,
but have doubtful or unproven efficacy:
Rifabutin
Macrolides:example: clarithromycin
Linezolid
Thioacetazone
Thioridazine

7.  New TB drugs under development:
 Bedaquiline
Delamanid (OPC-67683)
PA-824 and TBA-354
 AZD5847

8. New Previously treated
New sputum smear-positive,
New sputum smear-negative,
New extrapulmonary tuberculosis,
Others
Sputum smear-positive relapse,
Sputum smear-positive failure,
Sputum smear-positive treatment after
default,others
2H3R3Z3E3 + 4H3R3 2H3R3Z3E3S3 + 1H3R3Z3E3 + 5H3R3E3
2 months Intensive phase + 4 months
continuation phase
Four drugs at Thrice-weekly Schedule
for 2 months Intensive phase & Two
drugs at Thrice-Weekly Schedule for
remaining 4 months continuation phase.
3 months Intensive phase + 5 months
continuation phase
Five drugs at Thrice-weekly Schedule
for initial 2 months followed by Four
drugs for next 1 month Intensive
phase.Three drugs at Thrice-weekly
Schedule for remaining 5 months
continuation phase.

9. New: A patient who has never had treatment for TB or who has taken antituberculosis
drugs for less than 4 weeks.
Previously treated
(Re-treatment)
A patient who has taken TB treatment for 4 weeks or more in the past
and either relapsed, defaulted or had treatment failure.
Relapse A patient who received treatment and was declared cured or treatment
completed at the end of the treatment period and has now developed TB again.
These patients could be true relapses or have a new episode.
Re-treatment after
failure
A patient who received treatment and remained or became smear or
culture positive at the end of the treatment period.
Re-treatment after
default
A patient who completed at least one month of treatment and returns
after interrupting treatment for two months or more.
Other previously treated A patient who was previously treated but the outcome of previous TB treatment is unknown

10.  Defined as a form of TB infection caused by bacteria that are resistant to
treatment with at least two of the most powerful first line anti treatment TB
drugs, isoniazid (INH) and rifampicin (RMP).
 Extensively drug-resistant TB (XDR-TB): is a form of TB caused by organisms
that are resistant to isoniazid and rifampicin (i.e. MDR-TB) as well as any
fluoroquinolone and any of the second–line anti-TB injectable drugs (amikacin,
kanamycin or capreomycin
 Five percent (5%) of all TB cases across the globe in 2013 were estimated to be
MDRTB cases, including 3.5% of newly diagnosed TB cases, and 20.5% of
previously treated TB cases.
 State representative community based drug resistance surveys carried out in
the states of Gujarat (56m) and Maharashtra (105m) and Andhra Pradesh (85m)
estimate the prevalence of Multidrug resistant TB (MDR-TB) to be ~3% among
new TB cases and 12-17% among previously-treated TB cases.

11.  Most potent and bactericidal drugMost potent and bactericidal drug
 Tb can be treated effectively with INH+Rif aloneTb can be treated effectively with INH+Rif alone
 Mono-resistance to one of them can be treatedMono-resistance to one of them can be treated
effectively with a regimen containing the other agenteffectively with a regimen containing the other agent
with very low failure rate (2.5-5%)with very low failure rate (2.5-5%)
 So failure rate when INH+Rif resistant is 44% in non-So failure rate when INH+Rif resistant is 44% in non-
HIV and 70% in HIV patientsHIV and 70% in HIV patients

12.  When drug resistance is demonstrated in a patient who has never
received anti-TB treatment previously, it is termed primary
(Initial) resistance, i.e. TB patient’s initial M.TB population
resistant to drugs
 Secondary (Acquired) resistance is that which occurs as a result
of specific previous treatment, i.e. Drug-resistant M. TB in initial
population, selected by inappropriate drug use (inadequate
treatment or non-adherence)

13. Strains with genetic
drug resistance
Wild M. TB strain
Acquired drug
resistance
Primary drug
resistance
Spontaneous mutationSpontaneous mutation
Selection: inadequate treatmentSelection: inadequate treatment
TransmissionTransmission
Development of anti-tuberculosis drug resistanceDevelopment of anti-tuberculosis drug resistance
Pablos-Mendez et al. WHO, 1997Pablos-Mendez et al. WHO, 1997

14.  SOCIOLOGICAL FACTORS :
 Irregular intake
 inadequate duration
 Neglect of disease
 Ignorance

15. Drug resistance is more common in people who:
Do not take their TB medicine regularly
Do not take all of their TB medicines as told by their doctor or
nurse
Develop active TB disease again, after having taken TB medicine
in the past
Come from areas of the world where drug-resistant TB is
common
Have spent time with someone known to have drug-resistant TB
disease
Who is at risk for getting MDR TB?

16.  Most cases of acquired MDRTB are due to inappropriate treatment with a
single antiTB drug, usually INH. This can occur due to a medical provider,
such as a doctor or nurse, improperly prescribing, ineffective treatment, but
may also be due to the patient not taking the medication correctly, which can be
due to a variety of reasons, including expense or scarcity of medicines, patient
forgetfulness, or patient stopping treatment early because they feel better.

17. Mechanisms of M. tuberculosis drug resistance
Some of the ways the tubercle bacillus acquires drug resistance
are:
1)Cell wall: The cell wall of M. tuberculosis consists of complex lipids, and it
acts as a permeability barrier from drugs.
2) Drug modifying & inactivating enzymes: The M. tuberculosis genome
codes for certain enzymes that make it drug resistant. The enzymes usually
phosphorylate, acetylate, or adenylate the drug compounds.
3) Drug efflux systems
4) Mutations: Spontaneous mutations in the M. tuberculosis genome can give
rise to proteins that make the bacterium drug resistant, depending on the drug
action.

18. Examples of mutations that make M. tuberculosis drug
resistant:
 The mutation in the rpoB gene, which encodes
the beta subunit of the bacteria's RNA Polymerase.
↓
This mutation makes the bacillus resistant to Rifampicin.
 Non-resistant TB is sensitive to Rifampicin because this
drug binds to the beta subunit of the RNA Polymerase, and
hence disrupts translation and elongation.
 When the rpoB gene is mutated, the resulting beta subunit
protein has different amino acids, and thus a different
conformation. Rifampicin can no longer bind to the beta
subunit and prevent translation.

19.  Mutations leading to INH resistance have been
identified in different gene targets including katG, inhA,
ahpC and other genes that remain to be established.
↓
Amino acid replacements in the NADH binding site
of InhA apparently result in INH resistance by preventing
the inhibition of mycolic acid biosynthesis, which the
bacterium uses in its cell wall.
 Mutations in the katG gene causes the enzyme catalase
peroxidase unable to convert INH to its biologically active
form. Hence, INH is not able to affect M. tuberculosis.

20.  Require drug sensitivity testing can be by
 1. Detection of genes
 2.Drug sensitivity testing

21. The Drug sensitivity testing may be Direct or Indirect.
 Direct Method
 The clinical specimen in which AFB have been demonstrated in stained
smears, is subjected to digestion / decontamination process and used as the
inoculum. The advantage of this method is DST results are available along with
culture results. The inoculum used is representative of the bacillary population
present in the specimen.
 Indirect Test
 This test is used for specimens that are smear negative but culture
positive. Though the inoculum is standardized, it is not truly representative of
the bacillary population present and hence there exists a chance of selecting a
proportion of susceptible / resistant bacilli from the slope.

22.  Conventional Susceptibility Tests
 Three conventional techniques:
 Proportion method
 Absolute concentration and
 Resistance ratio

23. Proportion method.
 An equal quantity of a standardized inoculum of M. tuberculosis is seeded on a drug -
free and drug - containing medium.
 The drug free medium is seeded with an inoculum that is 100 times diluted compared
with that seeded on the drug - containing medium.
 Distinct, countable colony - forming units (CFU) should be present on the drug - free
medium.
 Thus to interpret as susceptible, the number of CFU on the drug medium must not exceed
those on drug free medium. This is the principle underlying the proportional method of
DST in MTB
 The proportion method can be performed on LJ or Middlebrook agar medium .The LJ
medium is recommended by the WHO as it is cheap, easy to read, has low contamination
rates and DST results are highly reproducible .
 Critical concentrations of drugs: The critical concentration (CC) is defined as the
Concentration that inhibits in-vitro growth of most MTB cells within the population of
wild type strains without appreciably affecting the growth of pre-existing resistant
mutants. If resistant mutants exceed 1%, the CC may not inhibit growth, and this predicts
therapeutic failure.

24.  The absolute concentration method
 An inoculum of M. tuberculosis is added to LJ or 7H10 / 7H11 agar containing
several sequential dilutions of each drug. Resistance is indicated by the lowest
concentration of the drug that inhibits growth, i.e . fewer than 20 colonies by the end
of 4 weeks.

The resistance ratio method
 The resistance ratio (RR) is the ratio of the minimum inhibitory concentration (MIC)
for the patients’ strain to the MIC of the drug susceptible reference strain, H37Rv,
both tested in the same experiment .
 After 4 weeks of incubation, growth on any slope is defined as the presence of 20 or
more colonies, and MIC is defined as the lowest drug concentration where the number
of colonies is less than 20. A resistance ratio of 2 or less indicates sensitive strain,
and a resistance ratio of 8 or more indicates resistant strains.
 The RR method is the most expensive of the three conventional methods.Conventional
tests have been time tested to offer very reproducible DST results and have been
considered as the gold standard tests for TB susceptibility testing.
 However, the DST process is very slow (2-3 months), necessitating the need for more
rapid assays.

25.  The following diagnostic technologies are currently available
under RNTCP and recommended for diagnosis of MDR-TB .
 MDR-TB diagnostic technology Choice
 Molecular DST [e.g. cartridge-based automated nucleic acid
amplification test (CBNAAT) or line probe assay (LPA)]
First
 Liquid culture isolation and LPA DST Second
 Solid culture isolation and LPA DST Third
 Liquid culture isolation and Liquid DST Fourth
 Solid culture isolation and DST Fifth

26.  Line Probe Assays
 A DNA strip test that allows simultaneous molecular identification of
tuberculosis and the most common genetic mutations causing resistance to
rifampicin and isoniazid that is rpoB gene conferring rifampicin resistance
and mutations on the katG gene which is associated with higher levels of
isoniazid resistance and inhA gene mutations which is associated with lower
levels of isoniazid resistance.
 These tests have been approved for direct testing on smear positive
specimens and on isolates from solid and liquid culture.
 In 2008, the WHO issued a recommendation for the use of molecular LPA
for the rapid diagnosis of MDR-TB in high TB-burden, low-income settings.
 The test that is available in the country is the Genotype MTBDRplus assay
which is a PCR based hybridisation assay.
 Compared to phenotypic DST this provides rapid diagnosis of drug resistant
TB and results should be available within 48 hours in the laboratory and 7
days in health facilities for smear positive TB. For smear negative TB, this
depends on the time to positive culture before the LPA can be performed.

30.  Advantages of the test are that:
 It detects MTB and resistance to RIF & INH at the same time from one
specimen
 It reduces time to diagnosis of MDR-TB to 7 days
 Cost-effective when compared with TB culture and DST
 They also demonstrated significant patient benefits, including early targeted
treatment of MDR-TB and the potential interruption of transmission.

31.  The limitations of the test are :
 It cannot be used for monitoring patients on treatment because it does not distinguish
between live and dead bacilli, therefore its use is limited to diagnosis
 It is dependent on smear results, can only be performed on smear positive or culture
positive sputum specimen
 labour intensive
 Prone to contamination and human error
 Requires a lot of space - at least 3 separate rooms for the different steps ( National
Tuberculosis Management Guidelines 2014)
 A small proportion of resistance detected may not correlate with physiological resistance
(leading to discordance between LPA and conventional DST results or clinical outcome).
 New:
 Version 2 of the MTBDRplus which can be used on smear positive and negative sputum
specimens is available and currently being validated in the country.
 MTBDRsl is available for second line testing. This test may be used as a rule in test for
XDR-TB in high risk groups.

32.  This is a heterogeneous group of tests that use either the polymerase chain
reaction (PCR) technique or Transcription mediated amplification (TMA) or
other forms of nucleic acid amplification methods to detect mycobacterial
nucleic acid.
 These test vary in which nucleic acid sequence they detect and vary in their
accuracy.
 sensitivity 92%
 specificity 99%

33.  Xpert® MTB/RIF (CBNAAT)
 The test is called Xpert MTB/RIF also
called as cartridge based nucleic acid
amplification test .
 The instrument is a GeneXpert (GXP).
 GeneXpert is an automated molecular
platform to detect M. tuberculosis and
rifampicin resistance testing by targeting
specific mutations in the rpoB gene. It is
approved for use directly on raw sputum
and results should be available within 2
hours in the laboratory but available in
health facilities within 48 hours.
 The test involves only three manual steps:
 The addition of sample treatment reagent
to liquefy and inactivate the sputum
 Transfer of 2ml of liquefied sputum to the
cartridge
 Loading the cartridge into the device for
the assay


34.  Advantages of the test are :
 It detects MTB and Rifampicin resistance from one specimen at
the same time.
 Results are available in approx. 2 hours.
 It is specific for MTB complex; (it can differentiate MTB from
other mycobacteria).
 It can also be used on the following processed samples - CSF,
aspirates (gastric, lymph node) and tissue (i.e. pleural biospy)
 The test for each specimen is carried out in a closed system
(cartridge), so there is a reduced risk of cross-contamination and
human error.

35.  The limitations of this test are :
 It cannot be used for monitoring treatment because it does not distinguish
between live and dead bacilli, its use is therefore limited to diagnosis
 A small proportion of Rifampicin resistance detected may not correlate with
physiological resistance (leading to discordance between Xpert and DST
results or clinical outcome)
 The assay is semi-quantitative and defines a positive test as “very low”,
“low”, “medium”, and “high”. This grading is not reported on the laboratory
result.
 There is no direct correlation between the Xpert semi-quantitative result and
the smear grading of scanty, +, ++ and +++. The rifampicin results can only
be reported if MTB complex is detected.
 The test might be unsuccessful due to laboratory test errors, test failure or
invalid results. In these instances a second specimen must be collected for a
repeat Xpert test.

36.  In 1969, Deland and Wagner developed a technique for semi-automated detection
of the metabolism of bacteria by measuring the 14CO2 liberated during the growth
and decarboxylation of 14C-labeled substrate incorporated in the growth medium.
This radiometric technique was widely used for blood culture using the BACTEC 460
instrument.
 In 1980, this technique was introduced commercially for mycobacterial recovery
from clinical specimens and drug susceptibility testing.
 One of the disadvantages of the BACTEC 460 TB System is the use of 14C-Labeled
radioactive substrate. Because of the strict regulations of handling and waste
disposal of radioactive material, it became necessary to develop a non-radiometric
technique for mycobacterial culture and susceptibility testing.
 Becton, Dickinson and Company (BD) developed a new system called Mycobacteria
Growth Indicator Tube (MGIT™), which is non-radiometric and offers the same rapid,
sensitive and reliable methods of testing as the BACTEC 460 TB System.
 BBL MGIT™ System is the manual system while BACTEC MGIT 960 (MGIT 960) is
the fully automatic system for detection of mycobacterial growth and drug
susceptibility testing of M. tuberculosis


37.  Principle of the BACTEC MGIT System
 Manual MGIT medium
 The MGIT contains 7.0ml of modified Middlebrook 7H9 broth base.
 In addition to Middlebrook 7H9 liquid media, the MGIT tube contains an
oxygen-quenched fluorochrome, tris 4, 7- diphenyl- 1, 10 - phenonthroline
ruthenium chloride pentahydrate, embedded in silicone at the bottom of the
tube.
 During bacterial growth within the tube, the free oxygen is utilized and is
replaced with carbon dioxide. With depletion of free oxygen, the fluorochrome
is no longer inhibited, resulting in fluorescence within the MGIT tube when
visualized under UV light.
 The intensity of fluorescence is directly proportional to the extent of oxygen
depletion and is indicative of the number of bacilli present.
 MGIT tubes may be incubated at 37ºC and read using the manual
transillumination with a 365nm UV light. (or entered into a MGIT 960
instrument where they are incubated and monitored for increasing fluorescence
every 60 minutes ).

38.  This medium is terminally sterilized by autoclaving.
 An enrichment, MGIT OADC (Oleic acid, Albumin, Dextrose and Catalase)
or MGIT Growth Supplement, is added to make the medium complete. This
growth supplement is essential for growth of many mycobacteria, especially
those belonging to M. tuberculosis complex.
 Addition of the MGIT PANTA, an antibiotic mixture is necessary to suppress
contamination.
 When supplemented with MGIT Growth Supplement and PANTA, it provides
an optimum medium for growth of a majority of mycobacterial species. All
types of specimens, pulmonary as well as extra - pulmonary (except blood),
can be inoculated into MGIT for primary isolation of mycobacteria.

39.  In case of M. tuberculosis, at the time of positivity, there are approximately 105
– 106
colony forming units (CFU) per ml of medium. The detection of growth
can also be visually observed by the presence of a non- homogeneous light
turbidity or small granular / flaky appearance in the medium. Growth of some
NTM (most commonly rapid growers) results in light turbidity, while
contaminating bacteria generally produce heavy turbidity.
 The instrument declares a tube negative if it remains negative for six weeks (42
days). Results of primary culture are available in 7 days.

40.  Drug susceptibility testing can be performed based on the same principle.
 Two MGIT tubes are inoculated with the test culture.
 A known concentration of a test drug is added to one of the MGIT tubes,
and growth is compared with the MGIT tube without the drug (growth
control).
 If the test drug is active against the isolated mycobacteria, it will inhibit the
growth and thus there will be suppression of fluorescence, while the growth
control will grow uninhibited and will have increasing fluorescence. Various
studies done showed the sensitivity to be 95%.Currently the MGIT system
exhibits greater potential as a rapid, accurate and cost effective method.

47.  Limitations
 Recovery of mycobacteria in the MGIT tube is dependent on the number of
organisms present in the specimen, specimen collection methods, patient factors
such as presence of symptoms, prior treatment and the method of processing.
 Decontamination with the N-acetyl-L-cysteine Sodium hydroxide (NALC-
NaOH) or Oxalic acid methods is recommended. Other decontamination
methods have not been tested in conjunction with the MGIT medium.
 Colony morphology and pigmentation can only be determined on solid media.
 MGIT tubes which appear positive may contain other non – mycobacterial
species.

49.  INTERPRETATION OF TESTS :
 First reading is taken at 28th day after inoculation.
 The average number of colonies obtained for the drug-containing slopes indicates the
number of resistant bacilli contained in the inoculum.
 Dividing the number of colonies in drug containing slopes by that in drug free slopes
gives the proportion of resistant bacilli existing in the strain.
 Below a certain value – the critical proportion – the strain is classified as sensitive; above
that value, it is classified as resistant. The proportions are reported as percentages.
 If, according to the criteria indicated below, the result of the reading made on the 28th
day is “resistant”, no further reading of the test for that drug is required: the strain is
classified as resistant.
 If the result at the 28th day is “sensitive”, a second reading is made on the 42nd day only
for the sensitive strain.
 In case growth on the control media is poor even after six weeks (i.e., few or no colonies
on the 10-4 bacterial dilution), the test should be repeated.

50.  MODS Microscopic Observation of Drug
Susceptibility Testing
 The observation that micro colonies could be seen under the microscope
long before a colour change occurred prompted the development of MODS.
 MBBacT system for isolates from automated mycobacterium cultures
 Colorimetric method based on oxidation reduction with indicator
Tetrazolium bromide.

51.  Prevention of emergence of MDR-TB in the community is more
imperative rather than its treatment.
 Early diagnosis of MDR-TB cases and adequately administered
treatment regimens are essential to control the further transmission
of disease.
 Revised National Tuberculosis Control Program uses a
standardized evidence-based regimen for treating MDR-TB cases.

52. Pretreatment Evaluation
 The patient should be hospitalized for pretreatment
evaluation and treatment initiation.
 Pretreatment evaluation includes
 Thorough clinical evaluation,
 CXR and
 Relevant hematological (complete blood count, blood sugar, liver
function tests) and biochemical tests (blood urea, S. Creatinine, TSH,
urine examination).
 A proper pretreatment evaluation is essential to identify
patients who are at increased risk of developing such
adverse effects from treatment.

53. Patients need to be counseled on :
 Nature and duration of treatment
 Need for regular treatment
 Possible side effects of drugs
 Consequences of irregular treatment or premature cessation of
treatment.
 It is advisable to involve close family members during the
counseling, since family support is an essential component in the
management.

54.  All patients should initially start a regimen for MDR-TB.
 Ideally, all MDR-TB patients should be screened for additional drug resistance
(second line DST) before initiating treatment. However, if laboratory capacity
for performing second line DST is constrained, then patient should be started on
MDR-TB treatment.
 All those patients who show culture-positivity as of 6-month and culture-
reversion at any time during the treatment must be subjected to second line DST
to stratify patients and offer appropriate treatment.

55.  Regimen for Multidrug Resistant Tuberculosis
 The treatment is given in two phases, the intensive phase (IP) and the
continuation phase (CP).
 This regimen comprises of six drugs—
 Kanamycin,
 Levofloxacin,
 Ethionamide,
 Pyrazinamide,
 Ethambutol and
 Cycloserine
6–9 months of the intensive phase
 Continuation phase :
 Four drugs —levofloxacin, ethionamide, ethambutol and cycloserine for
18 months

56.  All drugs should be given in a single daily dosage under
supervision.
 Pyridoxine should be administered to all patients on the regimen
for MDR-TB.
 The total duration of treatment for MDR-TB is 24–27 months,
depending on the IP duration.
 IP should be given for at least 6 months. After 6 months of
treatment, the patient will be reviewed and the treatment changed,
based upon the culture result.
 The IP can be extended up to a maximum of 3 months after which
the patient will be initiated on the CP irrespective of the culture
result. The recommended duration for CP is 18 months.

57.  The most important objective evidence of response to M/XDR
treatment is the conversion of sputum culture to negative.

 Smear conversion is less reliable than culture conversion, which
reflects viability of tubercle bacilli and is a more accurate
reflection of response to treatment.
 Patients will be considered culture converted after having two
consecutive negative cultures taken at least 1 month apart.

58. Clinical Monitoring
 Close monitoring of patients is necessary to ensure that the adverse
effects are recognized early.
 Patients should be seen by the practitioner for clinical evaluation at
monthly intervals during the IP, after discharge from the hospital, and at
3-monthly intervals during the CP, until the end of treatment.

59.  For follow-up examination:
 Sputum specimens will be collected and examined by smear
and culture at least 30 days apart from the 3rd–7th month of
treatment (i.e. at the end of the months 3, 4, 5, 6 and 7)
 and at 3-monthly intervals from the 9th month onwards till the
completion of treatment i.e. at the end of the months 9, 12, 15,
18, 21 and 24).

60. Prevention of MDR TB
There are several ways that drug resistance to TB, and drug
resistance in general, can be prevented:
1)Rapid diagnosis & treatment of TB: One of the greatest risk
factors for drug resistant TB is problems in treatment and
diagnosis, especially in developing countries. If TB is identified
and treated soon, drug resistance can be avoided.
2) Completion of treatment: Previous treatment of TB is an
indicator of MDR TB. If the patient does not complete his/her
antibiotic treatment, or if the physician does not prescribe the
proper antibiotic regimen, resistance can develop. Also, drugs
that are of poor quality or less in quantity, especially in
developing countries, contribute to MDR TB.

61. 3) Patients with HIV/AIDS should be identified and diagnosed as soon as
possible. They lack the immunity to fight the TB infection and are at great
risk of developing drug resistance.
4) Identify contacts who could have contracted TB: i.e. family members,
people in close contact, etc.
5) Research: Much research and funding is needed in the diagnosis,
prevention and treatment of TB and MDR TB.

62.  PMDT GUIDELINE , 2014
 Global report 2014 on Tuberculosis
 MGIT procedure manual, FIND manual
 RNTCP guideline on drug resistance
tuberculosis

63. THANK YOU