The bacteria that cause tuberculosis (TB) can develop resistance to the antimicrobial drugs used to cure the disease. Multidrug-resistant TB (MDR-TB) is TB that does not respond to at least isoniazid and rifampicin, the 2 most powerful anti-TB drugs. The 2 reasons why multidrug resistance continues to emerge and spread are mismanagement of TB treatment and person-to-person transmission. Most people with TB are cured by a strictly followed, 6-month drug regimen that is provided to patients with support and supervision. Inappropriate or incorrect use of antimicrobial drugs, or use of ineffective formulations of drugs (such as use of single drugs, poor quality medicines or bad storage conditions), and premature treatment interruption can cause drug resistance, which can then be transmitted, especially in crowded settings such as prisons and hospitals. In some countries, it is becoming increasingly difficult to treat MDR-TB. Treatment options are limited and expensive, recommended medicines are not always available, and patients experience many adverse effects from the drugs. In some cases even more severe drug-resistant TB may develop. Extensively drug-resistant TB, XDR-TB, is a form of multidrug-resistant TB with additional resistance to more anti-TB drugs that therefore responds to even fewer available medicines. It has been reported in 117 countries worldwide. Drug resistance can be detected using special laboratory tests which test the bacteria for sensitivity to the drugs or detect resistance patterns. These tests can be molecular in type (such as Xpert MTB/RIF) or else culture-based. Molecular techniques can provide results within hours and have been successfully implemented even in low resource settings. New WHO recommendations aim to speed up detection and improve treatment outcomes for MDR-TB through use of a novel rapid diagnostic test and a shorter, cheaper treatment regimen. At less than US$ 1000 per patient, the new treatment regimen can be completed in 9–12 months. Not only is it less expensive than current regimens, but it is also expected to improve outcomes and potentially decrease deaths due to better adherence to treatment and reduced loss to follow-up. Solutions to control drug-resistant TB are to: cure the TB patient the first time around provide access to diagnosis ensure adequate infection control in facilities where patients are treated ensure the appropriate use of recommended second-line drugs. In 2015, an estimated 480 000 people worldwide developed MDR-TB, and an additional 100 000 people with rifampicin-resistant TB were also newly eligible for MDR-TB treatment. India, China, and the Russian Federation accounted for 45% of the 580 000 cases. It is estimated that about 9.5% of these cases were XDR-TB.

1. DRUG RESISTANT TUBERCULOSIS
DR. MUTAFUNGWA ,GODFREY
RESIDENT 1
INTERNAL MEDICINE
UDOM

2. Remembering Sir John Crofton (1912–2009)
• Giant in the history of TB control.
• Initiator of the clinical trials
against TB using combined
regimens in the early 1950s.
• First to study and recognize the
importance of drug resistance in
TB.

3. • Multidrug-resistant TB (MDR-TB) :is a form
of TB caused by Mycobacterium tuberculosis
that are resistant in-vitro to at least isoniazid and
rifampicin.

5. • Extensively drug-resistant TB (XDR-TB) is
a subset of MDR-TB where the bacilli, in
addition to being resistant to R and H, are also
resistant to any fluoroquinolones and any one
of the second-line injectable drugs (namely
Kanamycin, Capreomycin, or Amikacin).

7. • These forms of TB do not respond to the standard
six month treatment with first-line anti-TB drugs
and can take two years or
more to treat with drugs that are less effective,
more toxic and more expensive.

8. EPIDEMIOLOGY
• WHO estimates that there were about 4,50,000 new(incident) mdr-tb cases in
the world in 2012.
• More than one half of these cases occurred in CHINA,INDIA & the RUSSIAN
FEDERATION.
• Enrolments on MDR-TB treatment in 2012: were equivalent to one in four of
the mdr-tb cases estimated to occur among pulmonary TB patients notified in
the world.
• Treatment success: 48% of patients with MDR-TB enrolled on treatment in
2010 were reported to have been successfully treated
• WHO estimates that there are about 650,000 MDR-TB cases in the world at any
one time.
• Only a small proportion of these cases are detected and treated appropriately
given that many low and lower middle-income countries still lack sufficient
diagnostic capacity to detect MDR/XDR-TB.

9. PROBLEM STATEMENT
MDR- TB
• Globally Prevalence of MDR- TB
• 3.4% in new TB patients
• 20% in those previously treated
• By October 2011, 77 countries had reported at least one case of XDR.
• Coverage is low particularly in the African continent as a result of low
capacity for testing for second-line medicines.
• WHO estimate that some 5% of people with multi drug resistant TB may
actually have extensively drug resistant TB.
Source: TUBERCULOSIS MDR-TB & XDR-TB 2011 PROGRESS REPORT (WHO)

10. COUNTRIES THAT HAD REPORTED AT LEAST
ONE
XDR-TB CASE BY OCT 2011

11. 1.3
MILLION
8.6 MILLION
estimated TB cases
5.7 MILLION
new cases diagnosed
and treated
MDR-TB
450,000
estimated new cases
the
burden
77,000
MDR-TB cases
diagnosed and on
treatment
XDR
45, 000
（10%）
estimated
cases of
XDR

12. GLOBAL TB
PROGRAMME
The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning
the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border
lines for which there may not yet be full agreement.
 WHO 2012. All rights reserved
Estimated number of MDR-TB Cases, 2011
>60% of all cases are in 6 countries
Russian Federation
44,000
(14% of global MDR burden)
India
66,000
(21% of global MDR
burden)
China
61,000
(20% of global MDR
burden)
Philippines
11,000
(4% of global
MDR burden)
Pakistan
10,000
(3% of global MDR
burden)
South Africa
8,100
Based on old
survey data

13. TANZANIAN SCENARIO
Tanzania : Tuberculosis profile
• High TB burden
• High HIV burden
• High MDR-TB burden

14. MDR-TB (Tanzania)
• 1.3% OF NEWLY DIAGNOSED TB CASES ARE MDR-TB CASES
• 4.7 % OF PREVIOUSLY TREATED TB CASES ARE MDR-TB CASES.
( Reported cases of MDR-TB 2015)
• Estimated MDR TB cases among notified PTB Cases 730
• Laboratory-confirmed MDR-TB cases 178 ,XDR TB 0
• Patients started on MDR-TB treatment 123
• Patients started on MDR-TB treatment 0
Data are as reported to WHO. Estimates of TB and MDR-TB Burden

15. Treatment Success rate
• New and relapse cases
registered in 2014 – 90%
• Previously treated cases
excluding relapse in 2014 –
81%
• HIV pos TB cases, all types
– 87%
• MDR/RR-TB cases on
second line, 2013 – 68%
• XDR TB on second line,2013
- 0

17. • XDR-TB has been reported in Tanzania by isolated studies
with non-representative and highly selected clinical samples.
• The magnitude of the problem remains to be determined due
to the absence of laboratories capable of conducting quality
assured second line DST.
• Preliminary results of second-line DST for MDR-TB patients
from DOTS Plus sites and also isolates collected from
Kibong’oto drug resistance surveys show that there is not yet
any XDR-TB amongst new cases and ~0.5% amongst re-
treatment cases.

18. WHY THIS EMERGENCE:CAUSES
• MULTIPLE INEFFECTIVE TB REGIMENS
• DELAYED DIAGNOSIS
• WRONG DOSE
• NON COMPLIANCE
• WRONG DURATION OF TREATMENT
• POOR QUALITY OF DRUGS
• CONTACT WITH A DRUG RESISTANT TB PATIENT
• CO-MORBIDITIES– HIV POSITIVE

19. MDR TB is a manmade
problem…..It is costly, deadly,
debilitating, and the biggest threat to
our current TB control strategies.

20. RISK FACTOR
• THE MOST IMPORTANT RISK FACTOR
FOR THE DEVELOPMENT OF DR-TB IS
PREVIOUS TREATMENT

21. DEVELOPMENT OF ANTI-TUBERCULOSIS
DRUG RESISTANCE
• PRIMARY or PRE-TREATMENT RESISTANCE-
When drug resistance is demonstrated in a patient who has never
received anti-TB treatment previously, it is termed primary resistance
• SECONDARY or ACQUIRED RESISTANCE-
Here the bacteria were sensitive to the drug at the start of the treatment
but became resistant to the particular drug during the course of the
treatment with it.

22. CAUSES OF DRUG RESISTANCE
Microbial:
• In m. Tuberculosis, acquired drug resistance is caused mainly by
spontaneous mutations in chromosomal genes, producing the
selection of resistant strains during sub-optimal drug therapy.
Clinical
• Due to inadequate treatment

23. Mechanism of drug resistance
The TB bacteria has natural defenses against some drugs, and can acquire
drug resistance through genetic mutations.
Some mechanisms of drug resistance include:
1. Cell wall: The cell wall of M. tuberculosis (TB) contains
complex lipid molecules which act as a barrier to stop drugs from entering
the cell.
2. Drug modifying & inactivating enzymes: The TB genome codes for
enzymes (proteins) that inactivate drug molecules. These enzymes
usually phosphorylate, acetylate, or adenylate drug compounds.
3. Drug efflux systems: The TB cell contains molecular systems that actively
pump drug molecules out of the cell.
4. Mutations: Spontaneous mutations in the TB genome can alter proteins
which are the target of drugs, making the bacteria drug resistant.

24. MECHANISM OF RESISTANCE
ANTIMICROBIAL
AGENT
MECHANISM OF ACTION MECHANISM OF RESISTANCE
ISONIAZID Inhibition of mycolic acid biosynthesis -Mutations in katG
-overexpression of inhA
-ahpC mutation
RIFAMPICIN Inhibition of transcription Mutation of rpoB prevent interaction
with rifampicin
STREPTOMYCIN Inhibition of protein synthesis Mutation prevent interaction with
streptomycin resistance .

25. MECHANISM OF RESISTANCE
ANTIMICROBIAL
AGENT
MECHANISM OF ACTION MECHANISM OF RESISTANCE
ETHAMBUTOL Inhibition of arabinogalactan and
lipoarabinomannan biosynthesis
Overexpression or mutation of Emb B
allow continuation of arabinan
biosynthesis
PYRAZINAMIDE Unknown
???
FLUORO-
QUINOLONE
Inhibition of the DNA gyrase Mutation in gyr A prevent interaction
with fluoro-quinolones

26. Drugs and associated mutations
DRUG ASSOCIATED GENE MUTATION
ISONIAZID (H) katG, inh A
RIFAMPICIN (R) rpoB
PYRAZINAMIDE (Z) pncA
STREPTOMYCIN (S) rrs,rpsl
ETHAMBUTOL (E) embB

27. CAUSES OF INADEQUATE
TREATMENT

28. Causes of emergence and potential
threat of XDR-TB
• Like all forms of drug-resistant tuberculosis, XDR-TB is human-made.
• MDR-TB can be amplified into XDR-TB by:
 Inadequate/interrupted treatment with second line anti-TB drugs.
 Indiscriminate use of second-line drugs.
 Non-adherence to national and/or international guidelines.
• Increasing use of fluoro-quinolones in combination with standard
first-line drugs esp. in new cases .
• Weak systems to ensure standardized regimens and treatment
adherence for MDR-TB

29. Many failures are due to
“failure to take the treatment”
and not
“failure of the treatment”

30. IMPACT OF DRUG RESISTANCE
• Prolonged illness
• Increased mortality
• Prolonged periods of infectiousness with increased risk of
transmission of resistant pathogens to others
• Indirect costs (prolonged absence from work, etc)
• Increased direct cost (longer hospital stay, use of more expensive
2nd or 3rd line drugs)
Huge individual as well as public health consequences in
terms of

31. MDR TB SUSPECT CRITERIA
MDR Suspect Criteria
Criteria A –
All failures of new TB cases
Smear +ve previously treated cases who remain smear +ve at 4th month onwards
All pulmonary TB cases who are contacts of known MDR TB case
Criteria B – in addition to Criteria A:
All smear +ve previously treated pulmonary TB cases at diagnosis
Any smear +ve follow up result in new or previously treated cases
Criteria C – in addition to Criteria B
All smear -ve previously treated pulmonary TB cases at diagnosis,
HIV TB co-infected cases at diagnosis

32. XDR TB –SUSPECT
Patients on category IV treatment whose 4th month culture is
positive (available after 6th month of treatment )
Category IV patient who has culture converted but is found
subsequently to have 2 consecutive positive cultures,
Source: DOTS Plus Guidelines, 2010

33. DIAGNOSTICS
Currently 3 technologies are available for diagnosis of
MDR TB viz.
 The conventional solid egg-based lowenstein-
jensen (LJ) media
 The liquid culture (Mycobact Growth Indicator Tube),
 The rapid molecular assays such as Line probe assay
(LPA) and similar nucleic acid Amplification Tests like
Xpert MTB/Rif.

34. MDR Diagnostic Technology Choice
Molecular DST (e.g. LPA DST) 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

35. The Line Probe assay (LiPA)
• Detect rpoB mutations of rifampicin and INH
• Rapid processing and reporting in less than 48
hours
• Drug susceptibility testing to second-line agents
(MTBDRsl)

37. Line Probe Assay (LPA)

38. Xpert MTB/RIF
• The Xpert MTB/RIF is based on the GeneXpert platform, a highly
sensitive, rapid and simple-to-use nucleic acid amplification
test (NAAT).
• The Xpert® MTB/RIF purifies, concentrates, amplifies (by real-time
PCR) and identifies targeted nucleic acid sequences in the TB
genome, and provides results from unprocessed sputum samples in
90 minutes, with minimal biohazard and very little technical training
required to operate

41. Reverse Line Blot Hybridization
Assay(RLBH).
• An in-house assay that could rapidly detect
resistance to drugs involved in the definition of
XDR-TB directly from smear-positive specimens.
• The results of RLBH are as accurate as other drug
susceptibility tests.
• RLBH testing only take 3 days to determine how
resistant the strain of bacteria was.

42. Direct nitrate reductase assay (D-NRA)
Showed efficient accuracy for the rapid and
simultaneous detection of resistance to isoniazid (INH),
rifampicin (RIF), kanamycin (KAN) and ofloxacin (OFL).
D-NRA results are obtained in 16.9 days,comparably
less than other drug susceptibility testing.
At the same time the D-NRA is a low-cost technology,
easy to set up in clinical laboratories and suitable to be
used for DST of M. tuberculosis in all smear-positive
samples

44. Summary of the study
• Conventional culture and drug susceptibility testing (DST)
methods for Mycobacterium tuberculosis are laborious and
time consuming.
• For this reason alternative rapid culture and DST techniques
are urgently needed to shorten the time for drug-resistance
detection.
• A total of 222 smear-positive sputum samples were evaluated
by the direct nitrate reductase assay (D-NRA) on
Lowenstein–Jensen medium, for the rapid and simultaneous
detection of resistance to isoniazid, rifampicin, kanamycin
and ofloxacin. p-Nitrobenzoic acid was also included for
identification of the M. tuberculosis complex.

45. • Results were compared with the BACTEC MGIT 960 as
gold standard.
• The general performance of the D-NRA was very good,
reaching a global value of 97%.
• D-NRA had a turn-around time of 16.9 days to obtain
results while that of the indirect MGIT 960 system was
29 days.
• D-NRA is a low-cost technology, easy to set up in
clinical laboratories and suitable to be used for DST of
M. tuberculosis in all smear-positive samples.

48. A NEWER CHEAP AND EFFECTIVE APPROACH IN TB
DIAGNOSTICS IS THE MODS(microscopic observation drug
sensitivity assay)
ADVANTAGE---
 cheaper,
 requires minimal staff training
 considerably faster compared to conventional liquid
culture based tests,
 can be implemented on a larger scale very rapidly as
compared to the very very costly equipments used for
LPA or NAAT

49. PRE-TREATMENT EVALUATION
• Since the drugs used for the treatment of
MDR-TB are known to produce adverse
effects, a proper pre-treatment evaluation is
essential to identify patients who are at
increased risk of developing such adverse
effects.

50. PRE-TREATMENT EVALUATION
The pre-treatment evaluation will include the following:
1. Detailed history (including screening for mental illness, drug/alcohol abuse etc.)
2. Weight
3. Height
4. Complete Blood Count with platelets count
5. Blood sugar to screen for Diabetes Mellitus
6. Liver Function Tests
7. Blood Urea and S. Creatinine to assess the Kidney function
8. TSH levels to assess the thyroid function
9. Urine examination – Routine and Microscopic
10. Pregnancy test (for all women in the child bearing age group)
11. Chest X Ray

51. ANTI-TUBERCULOSIS DRUGS BY
GROUP

52. TREATMENT
DOTS
PLUS(CAT 4)
REGIMEN
FOR MDR TB
DOTS CAT 5
REGIMEN
FOR XDR TB

53. DOTS PLUS
• DOTS-Plus refers to DOTS programmes that add
components for MDR-TB diagnosis, management and
treatment.
• The first WHO endorsed DOTS-Plus programmes began
in 2000.

54. STANDARDISED TREATMENT REGIMEN
For the treatment of MDR-TB cases
6 drugs
- kanamycin - ofloxacin
- ethionamide - pyrazinamide
- ethambutol - cycloserine
for 6-9 months of the Intensive Phase
56
TREATMENT

55. • CONTINUATION PHASE-
4 drugs
ofloxacin,
ethionamide
ethambutol
Cycloserine
for 18 months.
TREATMENT

56. FOR REGIMEN OF MDR TB
s.no drugs 16-25 Kg 26-45 Kg 46-70 Kg >70kg
1 Kanamycin(500&1G)
(IP)
500 mg 500mg 750mg 1000mg
2 Levofloxacin (250 &
500mg) (IP/CP)
250mg 750mg 1000mg 1000mg
3 Ethionamide (250mg)
(IP/CP)
375mg 500mg 750mg 1000mg
4 Ethambutol (200 &
800mg) (IP/CP
400mg 800mg 1200mg 1600mg
5 Pyrazinamide (500 &
750mg) (IP)
500mg 1250mg 1500mg 2000mg
6 Cycloserine (250mg)
(IP/CP)
250mg 500mg 750mg 1000mg
7 PAS (80%
Bioavailability)
5mg 10mg 12mg 12mg
8 Pyridoxine (100mg)
(IP/CP)
50mg 100mg 100mg 100mg

57. TREATMENT
• All drugs should be given in a single daily dosage
under directly observed treatment (DOT) by a DOT
Provider.
• If intolerance occurs to the drugs, ethionamide,
cycloserine and PAS may be split into two dosages.
• Pyridoxine at a dose of 100mg should be
administered to all patients on Category IV regimen.
• Patients which are not MDR but have any Rifampicin
resistance will also be treated with Cat IV regimen.

58. DOTS Plus Site
MDR TB Case admitted for evaluation and treatment
initiation
Patient discharged to the home
district with information to DTO
Daily DOT continued by a
trained DOT Provider
Follow up Protocol
Smear and Culture monthly during IP and Quarterly during CP
Physical evaluation monthly during IP and Quarterly during CP by the DTO
KFT and other investigations at regular intervals
Patient flow …. Treatment and follow up

59. Follow up smear and culture schedule
during treatment
Two specimens for AFB (one early
morning and one supervised spot) will
be collected and examined at the
respective DMC/DTC (at the end of the
months 3, 4, 5, 6, 7, 9, 12, 15, 18, 21
and 24).
Two specimens for culture (one early
morning and one supervised spot) will
be collected and transported in CPC
bottles from the respective DTC to the
RNTCP accredited laboratory (at the
end of the months 3, 4, 5, 6, 7, 9, 12,
15, 18, 21 and 24).
If any of the cultures in the last three quarters becomes positive, it will
be followed up by monthly cultures in the following 3 months

60. Contd.
After 6 months of
treatment (Intensive
phase)
Patient will be reviewed
and the treatment
changed to CP if the 4th
month culture result is
negative
If the result of the 4th
month culture is still
awaited after 6 months of
treatment, the IP is
extended until the result
is available.
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

61. TREATMENT INTERRUPTION AND
DEFAULT
• Cat IV patients in IP/CP who miss doses:
• All the missed doses during IP must be completed prior to switching
the patient to CP.
• Similarly all missed doses during CP must be administered prior to
ending treatment.
• Cat IV patients who interrupt treatment for less than 2 months
during IP:
• When the patient returns to resume treatment the IP will be
continued, however the duration of treatment will be extended to
complete IP.
• The follow up cultures will be done as per the revised schedule.

62. TREATMENT INTERRUPTION AND
DEFAULT
• Cat IV patients who interrupt treatment for less than 2 months
during CP:
• When the patient returns to resume treatment, the CP will be
continued, however the duration of treatment will be extended to
complete the CP.
• The follow up cultures will be done as per the revised schedule.
• Cat IV patients who default (interrupt treatment for 2 or more
months) and return back for treatment:
• Such patients will be given an outcome of “default” and then will be
re-registered for further treatment which is based on the duration of
default.
• Re-registration of patients will be done by the DOTS Plus site.

63. Standardised treatment outcome
definitions
• Cure: An MDR-TB patient who has completed treatment and has
been consistently culture negative (with at least 5 consecutive
negative results in the last 12 to 15 months).
• If one follow-up positive culture is reported during the last three
quarters, patient will still be considered cured provided this positive
culture is followed by at least 3 consecutive negative cultures, taken
at least 30 days apart, provided that there is clinical evidence of
improvement.
• Treatment completed:An MDR-TB patient who has
completed treatment according to guidelines but does not meet the
definition for cure or treatment failure due to lack of bacteriological
results.

64. Management Guidelines for
Patients with XDR-TB
• Use any Group 1 agents that may be effective.
• Use an injectable agent to which the strain is susceptible and
consider an extended duration of use (12 months or possibly the
whole treatment). If resistant to all injectable agents, it is
recommended to use one the patient has never used before.
• Use a later-generation fluoroquinolone such as moxifloxacin.
• Use all Group 4 agents that have not been used extensively in a
previous regimen or any that are likely to be effective.

65. Management Guidelines for
Patients with XDR-TB
• Use two or more agents from Group 5.
• Consider high-dose isoniazid treatment if low-level resistance is
documented.
• Consider adjuvant surgery if there is localized disease.
• Ensure strong infection control measures.
• Treat HIV
• Provide comprehensive monitoring

66. REGIMEN FOR XDR-TB
• Intensive phase (6-12 months) consist of 7
drugs –
capreomycin (cm), PAS,moxifloxacin (mfx), high
dose-inh, clofazimine, linezolid, and amoxyclav
• Continuation phase (18 months) consist of 6
drugs –
PAS, moxifloxacin (mfx),high dose-inh,
clofazimine, linezolid, and amoxyclav

67. DRUGS
Dosage/day
<= 45kgs >= 45kgs
Inj. Capreomycin(cm) 750mg 1g
PAS 10gm 12gm
Moxifloxacin (Mfx) 400mg 400mg
High dose INH (High
dose-H)
600mg 900mg
Clofazimine (Cfz) 200mg 200mg
Linezolid (Lzd) 600mg 600mg
Amoxyclav(Amx/Clv) 875/125mg bd 875/125 mg bd
Pyridoxine 100mg 100mg
DRUGS USED FOR XDR-TB

68. TREATMENT ALGORITHM OF DRUG RESISTANT TB
MDR TBMDR TB
START RNTCP MDR TB
REGIMEN
START RNTCP MDR TB
REGIMEN
AT THE END OF IP THE RESULT OF MOST
RECENT CULTURE
POSITIVE NEGATIVE
EXTEND IP FOR 1 MONTH AT A TIME, FOR UP TO 3 MONTHS MAX,
TILL AT LEAST A SUBSEQUENT NEGATIVE FOLLOW-UP CULTURE RESULT
IS OBTAINED.
START CP
CULTURE POSITIVE EVEN AFTER 9 MONTHS OR
CULTURE RE-VERSION
SECOND LINE DST
IF OFX & KM
SENSITIVE
IF OFX &/or KM
RESISTANT
CONTINUE MDR
TB REGIMEN
START REGIMEN
FOR XDR TB

69. ROLE OF SURGERY
• In MDR-TB patients with localized disease, surgery, as an adjunct to
chemotherapy, can improve outcomes provided skilled thoracic surgeons
and excellent post-operative care are available.
• When unilateral resectable disease is present, surgery should
be considered for the following cases:
• Absence of clinical or bacteriological response to chemotherapy despite six
to nine months of treatment with effective anti-tuberculosis drugs;
• High risk of failure or relapse due to high degree of resistance or extensive
parenchymal involvement;

70. ROLE OF SURGERY
• Morbid complications of parenchymal disease e.g. haemoptysis,
bronchiectasis, broncho-pleural fistula, or empyema;
• Recurrence of positive culture status during course of treatment
• Relapse after completion of anti-tuberculosis treatment.
• If surgical option is under consideration at least six to nine
months of chemotherapy is recommended prior to surgery.

71. MDR-TB IN SPECIAL SITUATIONS
PREGNANCY
All women of childbearing age who are receiving MDR-TB therapy
should be advised to use birth control measures because of the
potential risk to both mother and foetus
CONSENT
FOR MTP?
NO
YES
<12 WEEKS
GESTATION
>12 WEEK
GESTATION
Km & ETO ARE REPLACED
WITH PAS
ONLY Km IS REPLACED
WITH PAS
REPLACE PAS WITH Km AFTER DELIVERY

72. MDR- TB is more common in HIV positive patients because
• People living with HIV
– have weakened immune systems which left them vulnerable to
TB.
– socially vulnerable populations, including injecting drug users
– Socio-behavioural problems and/or lack of access to proper care
may make these populations, as TB patients,
– vulnerable to developing drug resistance as a result of poor
adherence to treatment or suboptimal treatment.
MDR- TB AND HIV

73. MDR- TB AND HIV
The epidemiological impact of HIV infection on the transmission of
MDR-TB :
• HIV positive TB cases are more likely to be sputum smear negative,
and therefore less likely to transmit TB.
• Delayed diagnosis of drug resistance have led to high death rates in
people living with HIV, which may also result in a lower rate of TB
transmission.

74. Challenges in the treatment of MDR- TB with HIV
• Diagnosis of TB is more difficult in HIV positive people
– Smear negative; Extra-pulmonary
• Treatment is challenging
– Drug interactions
– Intolerance and non-adherence
• Protecting health care workers (HCWs) is important
– Special risk for HIV+ MDR - TB
MDR- TB AND HIV

75. RENAL IMPAIRMENT
• Drugs, which might require dose or interval
adjustment in presence of mild to moderate renal
impairment are:
ethambutol, quinolones, cycloserine and PAS in
addition to aminoglycosides
• Blood and serum creatinine every month for the first
3 months and then every 3 months

76. Liver impairement
• In the Regimen for MDR TB, Pyrazinamide, PAS
and Ethionamide are potentially hepatotoxic drugs.
• The further management should be on the same
guidelines as in non- MDR-TB patients
• Pyrazinamide should be avoided in such patients.

77. Seizure disorder
• Among second line drugs, Cycloserine, Ethionamide and
fluoroquinolones have been associated with seizures, and
hence should be used carefully amongst MDR-TB patients
with history of seizures
• Pyridoxine should be given with Cycloserine to prevent
seizures
• Cycloserine should however be avoided in patients with
active seizure disorders that are not well controlled with
medication.
• when seizures present for the first time during anti-TB
therapy, they are likely to be the result of an adverse effect of
one of the anti-TB drugs.

78. Psychosis
• Fluoroquinolones ,cycloserine and Ethionomide
have been associated with psychosis.
• Cycloserine may cause severe psychosis and
depression leading to suicidal tendencies.
• If patient on Cycloserine therapy develops psychosis,
anti-psychotic treatment should be started and
Cycloserine therapy should be temporarily suspended.
• Pyridoxine prophylaxis may minimize risk of neurologic
and psychiatric adverse reactions.

79. Extra pulmonary mdr tb
• Treatment regimen and schedule for EP MDR TB
cases will remain the same as for pulmonary MDR
TB.

80. Contacts of mdr tb
• If the contact is found to be suffering from
pulmonary TB disease irrespective of the Smear
results, he/she will be identified as an “MDR-TB
suspect”
• The patient will be initiated on Regimen for new or
previously treated case based on their history of
previous anti-TB treatment.
• Simultaneously two sputum samples for culture

81. Laboratory networking in Tanzania
L
A
B
O
R
A
T
O
R
Y
S
E
R
V
I
C
E
S
The program laboratory networking consists of three levels;
one central reference laboratory at
Muhimbili National Hospital also called the Central
Tuberculosis Reference Laboratory (CTRL),
Two TB zone laboratories (Bugando Medical Centre and
Kilimanjaro Christian Medical Centre) and
995 diagnostic centres at peripheral health centres levels.

82. • In 2010 the Kibong’oto hospital received approval
from the World Health Organisation (WHO) to be
responsible for all treatment of patients with
multiresistant tuberculosis (MDR-TB) in Tanzania.

83. BCG Vaccine
The BCG vaccine prevents severe forms of TB in children, such
as TB meningitis.
It would be expected that BCG would have the same effect in
preventing severe forms of TB in children, even if they were
exposed to XDR-TB.
The vaccine has shown to be less effective at preventing the
most common strains of TB and in blocking TB in adults.
The effect of BCG against XDR-TB would therefore likely be
very limited.
New vaccines are urgently needed, and WHO and members of
the Stop TB Partnership are actively working on new vaccines.

84. Totally drug-resistant
tuberculosis (TDR-TB)
• Is a generic term for tuberculosis strains that
showed in vitro resistance to all first and
Second line drugs tested.
• TDR-TB has been identified in three countries;
India, Iran, and Italy.
• Center for disease control and prevention
termed the disease “untreatable”

85. • TDR-TB has resulted from further mutations within
the bacterial genome to confer resistance, beyond
those seen in XDR- and MDR-TB.
• Development of resistance is associated with poor
management of cases.
• Drug resistance testing occurs in only 9% of TB
cases worldwide.

86. • Without testing to determine drug resistance
profiles, MDR- or XDR-TB patients may develop
resistance to additional drugs.
• TDR-TB is relatively poorly documented, as many
countries do not test patient samples against a
broad enough range of drugs to diagnose such a
comprehensive array of resistance.

87. The case of Mumbai and the
“TDR-TB outbreak”
Udwadia ZF, Amale RA, Ajbani KK, Rodrigues C. Totally drug-resistant
tuberculosis in India. Clin Infect Dis. 2012 Feb 15;54(4):579–81.

88. PREVENTION
There are several ways that drug resistance to TB, and drug
resistance in general, can be prevented:
 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.
 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.

89. 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.
Identify contacts who could have contracted TB: i.e.
family members, people in close contact, etc.
Research: Much research and funding is needed in
the diagnosis, prevention and treatment of TB and
MDR TB.

90. FUNDING FOR MDR
• According to the 2011 WHO Global TB report, funding for MDR-TB in
2011 was US$0.7 billion, US$ 0.2 billion less than the need
estimated in the Global Plan to Stop TB.
• The funding required for MDR-TB to reach the 2015 target of
universal access to care rises from US$ 0.9 billion in 2011 to US$ 2
billion in 2015; most of this funding is needed in middle-income
countries.
• Thus, much more funding needs to be mobilized in high MDR-TB
burden countries to ensure proper diagnosis and treatment.

92. Bill Gates' donates millions to battle
TB
• Many more
powerful hands
needed to
Control
Tuberculosis

93. Contribute your Knowledge, Wisdom, to
prevent spread and control of Tuberculosis