Tuberculosis suspect. Productive cough for more than 2 weeks, which may be accompanied by other respiratory symptoms and/or constitutional symptoms Case of tuberculosis. A definite case of TB or one in which a health worker (clinician or other medical practitioner) has diagnosed TB and has decided to treat the patient with a full course of TB treatment. Any person given treatment for TB should be recorded as a case. Incomplete “trial” TB treatment should not be given as a method for diagnosis.

1. UPDATE IN
TUBERCULOSIS
Dr. Sachin Verma MD, FICM, FCCS, ICFC
Fellowship in Intensive Care Medicine
Infection Control Fellows Course
Consultant Internal Medicine and Critical Care
Ivy Hospital Sector 71 Mohali
Web:- http://www.medicinedoctorinchandigarh.com
Mob:- +91-7508677495
Page 1

2. Discovery of Mycobacterium
tuberculosis
Tribute to Robert Koch
Page 2

3. Outline
• Why a fourth edition
• New recommendations
• Integrating MDR prevention, diagnosis,
and treatment into the National TB
Program (NTP).
3 Page 3

4. Universal access to quality TB care
for all TB patients
•No longer assign lower priority to patients
with smear negative or MDR disease
(formerly Category 3, 4)
•Detection and treatment of MDR-TB should
be an integral part of NTP activities
4 Page 4

5. Prior WHO guidelines
• Not evidence-based
• Too much dependence on expert
opinion
• Decisions not transparent
Oxman, Lancet 2007; 369
5 Page 5

6. New WHO requirements for guidelines:
formulate questions
• Duration of rifampicin in new patients
• Dosing frequency in new patients
• TB treatment in people living with HIV
• Sputum monitoring and treatment extension
• Regimen for new TB patients in countries with
high levels of isoniazid resistance
• Use of the 8 month retreatment regimen with first
line drugs (“Cat 2”)
6 Page 6

7. Strength of recommendations
• Strong (“should”): desirable effects clearly
outweigh undesirable
– High quality evidence, large certain benefit
• Conditional (“may”): trade offs are uncertain
– Evidence is lacking or low quality
– Benefits small or difficult to quantify, may not justify
cost
• Weak: insufficient evidence (based on field
application and expert opinion)
• Not rated: quality of evidence not assessed.
7 Page 7

8. Key changes since the third
edition
Instead of “Diagnostic categories I–IV”,
this edition uses the same patient
registration groups used for recording
and reporting, which differentiate new
patients from those with prior treatment
and specify reasons for retreatment.
Page 8

9. Page 9

10. NO category, NO 2HRZ/4HR,NO 2HRZE/6HE
Page 10

11. Registration group by outcome of most recent TB treatment
Page 11

12. New guideline
1. New patient regimen : 2 HRZE/4HR Cat I
2. Retreatment regimen with first line
Cat II
drug : 2SHRZE/HRZE/5HRE
Page 12

13. New guideline
• Tuberculosis suspect. Productive cough for more than 2
weeks, which may be accompanied by other respiratory
symptoms and/or constitutional symptoms
• Case of tuberculosis. A definite case of TB or one in
which a health worker (clinician or other medical
practitioner) has diagnosed TB and has decided to treat the
patient with a full course of TB treatment.
• Any person given treatment for TB should be recorded as
a case. Incomplete “trial” TB treatment should not be given
as a method for diagnosis.
Page 13

14. New guideline
• The recent WHO case definition for sputum smear-positive
pulmonary TB has been applied to a definite case of TB.
• A patient with one positive AFB smear is considered a
definite case. (In the third edition, two positive smears were
required before a patient could be considered a definite
case.)
• There is reduction in the number of specimens from three
to two for screening patients suspected to have TB.
Page 14

15. Duration of rifampicin in new patients
Should new pulmonary TB patients be treated with the
6-month rifampicin regimen (2HRZE/4HR)
or
2-month rifampicin regimen (2HRZE/6HE)?
Page 15

16.  Recommendation 1
New patients with pulmonary TB should receive a
regimen containing 6 months of rifampicin: 2HRZE/4HR
Also applies to extrapulmonary TB, except TB of the
central nervous system, bone or joint for which some expert
groups suggest longer therapy
(Strong/High grade of evidence)
Recommendation 2
The 2HRZE/6HE treatment regimen should
be phased out*
(Strong/High grade of evidence)
Page 16

17. Initial regimen in countries with high
levels of isoniazid resistance
Recommendation 1
2HRZE/4HRE
In populations with known or suspected
high levels of isoniazid resistance,
new TB patients may receive HRE as
therapy
in the continuation phase as an acceptable
alternative to HR
(Weak/Insufcient evidence, expert opinion)
Page 17

18. Why concern about Isoniazid
resistance in new patients?
• Outcomes are significantly worse than for patients with
isoniazid susceptible disease
– Risk of failure 11x higher, and relapse 2x higher
• It’s a stepping stone to MDR
– 5x higher risk of acquired drug resistance
• It’s common: Globally, 7% of new patients resistant to at
least isoniazid (but not yet to rifampin).
18 Page 18

19. Standard Regimens For New TB patients
In presumed, or known, to have drug-susceptible TB
who no longer recommends omission of ethambutol during the intensive
phase of treatment for patients with non-cavitary, smear-negative pTB or
epTB who are known to be HiV-negative. in tuberculous meningitis,
ethambutol should be replaced by streptomycin.
In settings where the level of isoniazid resistance among new TB cases
is high and isoniazid susceptibility testing is not done (or results are not
available) before the continuation phase begins)
Page 19

20. Dosing frequency in new patients
Recommendation 1
Wherever feasible, the optimal dosing frequency for new patients
with pulmonary TB is daily throughout the course of therapy
(Strong/High grade of evidence)
Recommendation 1.1
New patients with pulmonary TB may receive a daily intensive
phase followed by a three times weekly continuation phase
[2HRZE/4(HR)3]provided that each dose is directly observed
(Conditional/High and moderate grade of evidence)
Recommendation 1.2
Three times weekly dosing throughout therapy 2(HRZE)3/4(HR)3]
may be used as another alternative to Recommendation 1.1,
provided that every dose is directly observed and the patient is NOT
living with HIV or living in an HIV-prevalent setting
(Conditional/High and moderate grade of evidence)
Page 20

21. Dosing frequency for new TB patient
Page 21

22. Recommendation 2
New patients with TB should not receive twice
weekly dosing for the full course of treatment unless
this is done in the context of formal research
(Strong/High grade of evidence)
Page 22

23. Tb treatment in persons living with HIV TB
patients living in HIV prevalent settings
Recommendation 1
TB patients with known positive HIV status and all TB patients living
in HIV prevalent settings should receive daily TB treatment at least
during the intensive phase
(Strong/High grade of evidence)
Remark
HIV-prevalent settings are defined as countries, subnational administrative units,
or selected facilities where the HIV prevalence among adult pregnant women is
≥1% or among TB patients is ≥5%
Page 23

24. Page 24
World health Organization Global Tuberculosis Control A short update to the 2009 report

25. Recommendation 2
For the continuation phase, the optimal dosing frequency is
also daily for these patients
(Strong/High grade of evidence)
Recommendation 3
If a daily continuation phase is not possible for these
patients, three times weekly dosing during the continuation phase is
an acceptable alternative
(Conditional/High and moderate grade of evidence)
 Recommendation 4
It is recommended that TB patients who are living with HIV
should receive at least the same duration of TB treatment as HIV-
negative TB patients
(Strong/High grade of evidence)
Page 25

26. Page 26

27. Treatment extension in new pulmonary
Tb patients
Recommendation 1
In patients treated with the regimen containing
rifampicin throughout treatment, if a positive sputum
smear is found at completion of the intensive phase, the
extension of the intensive phase is not recommended
(Strong/High grade of evidence)
Page 27

28. Smear status at the end of the intensive
phase
1. Poor predictor of which new patients will relapse.
2. However, detection of a positive sputum smear remains
important as a trigger for the patient assessment,
quality of patient’s support and supervision and
intervention promptly if necessary
3. Continue HR and sputum monitoring on month 3 if
specimen obtained at the end of month 3 is smear
positive sputum culture and drug susceptibility testing
should be performed
Page 28

29. A positive sputum smear at the end of the intensive
phase may indicate any of following
1. the initial phase of therapy was poorly supervised and
patient adherence was poor
2. poor quality of anti-TB drugs
3. doses of anti-TB drugs are below the recommended
range
4. resolution is slow because the patient had extensive
cavitation and a heavy initial bacillary load;
5. non-viable bacteria remain visible by microscopy.
Page 29

30. Sputum monitoring, new patients
Recommendations (Strong): if specimen obtained at
end of intensive phase is smear +, repeat at end of
third month. If still positive, obtain culture and DST
Failure: + bacteriology
at 5th month or later, or
MDR detected any time
30 Page 30

31. Previously treated patients
Recommendation 1
Specimens for culture and drug susceptibility testing (DST)
should be obtained from all previously treated TB patients at or
QUESTION of treatment. DST should be performed for at least
before the start 1
isoniazid and rifampicin
Recommendation 2
In settings where rapid molecular-based DST is available, the
results should guide the choice of regimen
Page 31

32.  Recommendation 3
In settings where rapid molecular-based DST results are
not routinely available to guide the management of individual
patients, empirical treatment should be
started as follows:
Recommendation 3.1
TB patients whose treatment has failed or other patient
groups with high likelihood of multidrug-resistant TB
(MDR-TB) should be started on an empirical MDR regimen
Recommendation 3.2
TB patients returning after defaulting or relapsing from
their first treatment course may receive the retreatment
regimen containing first-line drugs 2HRZES/1HRZE/5HRE
if country-specific data show low or medium levels of MDR
in these patients or if such data are unavailable
Page 32

33. Recommendation 4
In settings where DST results are not yet routinely
available to guide the management of individual patients, the
empirical regimens will continue through out the course of
treatment
Page 33

34. Previously treated patients
Weighted mean of MDR-TB in new MDR in retreatment TB cases from drug
and retreatment TB cases from resistance surveysand surveillance in
drug resistance surveys, 1994–2007 10 countrieS, 1997–2007
Page 34

35. Type of Results Approach to retreatment
DST available
Rapid Hours to Use DST results to decide
days if MDR regimen needed
Conventional Days to Start empiric regimen while
weeks awaiting DST results.
Once DST results
available, may change
regimen.
None Not Use empiric regimen for
(Interim) available full course of treatment.
35 Page 35

36. MDR likelihood
(patient registration group)
Type of High Medium
DST (after failure) (relapse, default)
Rapid DST results guide choice of regimen
from the start
While awaiting DST results (empiric):
MDR regimen 2HRZES/HRZE/5HRE
Conventional
Modify on basis of DST results once
available
None Interim 36 Page 36

37. Country-specific drug resistance
data country-specific drug
NTPs should obtain and use their
resistance data on failure, relapse and default patient
groups to determine the levels of MDR (rec #7.5)
Need to verify or modify the assignment of:
• Failure patients to high likelihood of MDR
• Relapse and default patients to moderate likelihood of
MDR
37 Page 37

38. Sputum monitoring, previously treated
patients on first line drugs
Recommendation (Strong): if specimen obtained at
end of intensive phase is sm +, obtain culture, DST
38 Page 38

39. Multi-drug Resistant Tuberculosis
(MDR TB)
Page 39

40. DEFINATIONS
• MDR (Multidrug resistant tuberculosis)
resisted to at least H, R
• XDR (Extensive drug resistant tuberuculosis)
strain of MDR-TB which also resisted to any one
member of fluoroquinolones and one of injected
anti-TB drugs : kanamycin, amikacin,
capreomycin
Page 40

41. Page 41

42. Page 42

43. Page 43

44. Page 44

45. Page 45

46. Management Side Effect Of
Antituberculosis
Page 46

47. Page 47

48. Page 48

49. management of cutaneous reactions
itching without a rash and there is no other obvious cause
symptomatic treatment with antihistamines and skin moisturizing,
and continue TB treatment while observing the patient closely
skin rash develop
all anti-TB drugs must be stopped. Once the reaction has
resolved, anti-TB drugs are reintroduced one by one,
starting with the drug least likely to be responsible for the
reaction (rifampicin or isoniazid) at a small challenge dose, such as
50 mg isoniazid
dose is gradually increased over 3 days. This procedure is
repeated, adding in one drug at a time. A reaction after adding in a
particular drug identifes that drug as the one responsible for the
reaction.
Page 49
WHO Treatment of tuberculosis guideline 2010

50. Management of antituberculosis induce hepatitis
Of the first-line anti-TB drugs, isoniazid, pyrazinamide and rifampicin
can all cause liver damage
The management of hepatitis induced by TB treatment depends on:
— whether the patient is in the intensive or continuation phase of
TB treatment;
— the severity of the liver disease;
— the severity of the TB
Page 50

51. All drugs should be stopped
If the patient is severely ill with TB and it is considered
unsafe to stop TB treatment, a non-hepatotoxic regimen
consisting of streptomycin, ethambutol and a
fuoroquinolone should be started.
If TB treatment has been stopped, it is necessary to wait
for liver function tests to revert to normal and clinical
symptoms (nausea, abdominal pain) to resolve before
reintroducing the anti-TB drugs.
Page 51

52. Once drug-induced hepatitis has resolved, the drugs are
reintroduced one at a time. If symptoms recur or liver
function tests become abnormal as the drugs are reintro-
duced, the last drug added should be stopped.
Some advise starting with rifampicin because it is less
likely than isoniazid or pyrazinamide to cause
hepatotoxicity and is the most efective agent After 3–7
days, isoniazid may be reintroduced.
In patients who have experienced jaundice but tolerate
the reintroduction of rifampicin and isoniazid, it is
advisable to avoid pyrazinamide.
Page 52

53. Alternative Regimen
If rifampicin cannot be used………………………2SHE/10HE)
regimen without rifampicin is 2 months of isoniazid, ethambutol
and streptomycin followed by 10 months of isoniazid and
ethambutol.
If isoniazid cannot be used………………………........(6-
9RZE)
6–9 months of rifampicin, pyrazinamide and ethambutol
If pyrazinamide cannot be used…………………..(2HRE/7HR)
before the patient has completed the intensive phase, the total
duration of isoniazid and rifampicin therapy may be extended to 9
months
If neither isoniazid nor rifampicin can be used….8-24 EOS)
the non-hepatotoxic regimen consisting of streptomycin,
ethambutol and a fuoroquinolone should be continued forPage 53 of
a total

54. Treatment of extrapulmonary TB
and of TB in special situations
Page 54

55. Treatment of extrapulmonary Tb
Pulmonary and extrapulmonary disease should be treated with
the same regimens
some experts recommend 9–12 months of treatment for TB
meningitis and 9 months of treatment for TB of bones or joints
Unless drug resistance is suspected
adjuvant corticosteroid treatment is recommended for TB
meningitis and pericarditis
In tuberculous meningitis,ethambutol should be replaced by
streptomycin.
fourth edition no longer includes the option of omitting
ethambutol during the intensive phase of treatment(2HRZ/4HR)
for patients with extrapulmonary disease who are known to be
HIV-negative
Page 55

56. Length Of tuberculosis therapy
Page 56
MMWR 200352:63-64

57. HIV
• Irrespective of epidemic setting, WHO recommends HIV
testing for patients of all ages who present with signs or
symptoms that suggest tuberculosis , whether TB is
suspected or already confirmed.
• The first priority for HIV-positive TB patients is to initiate
TB treatment, followed by co-trimoxazole and ART .
• ART should be initiated for all people living with HIV with
active TB disease irrespective of CD4 cell count.
• TB treatment should be started first, followed by ART as
soon as possible and within the first 8 weeks of starting
TB treatment
Page 57

58. • WHO recommends that the first-line ART regimen contain two
.
nucleoside reverse transcriptase inhibitors (NRTIs) plus one
non-nucleoside reverse transcriptase inhibitor (NNRTI).
• The recommended first-line ART regimens for TB patients are
those that contain efavirenz (EFV), since interactions with anti-
TB drugs are minimal.
• efavirenz should not be used in women of childbearing potential
without adequate contraception, nor should it be used for
women who are in the first trimester of pregnancy.
• WHO recommends that NTPs undertake DST at the start of TB
therapy in all HIV-positive TB patients, to avoid mortality due to
unrecognized drug-resistant TB .
Page 58

59. NACO GUIDELINE
TYPE OF TB CD4 COUNT INITIATION OF ART
PULMONARY < 350 BETWEEN 2 WEEKS
TO 2 MONTHS
ZDV(D4T)+3TC+EFV
EXTRAPULMONARY ALL HIV + BETWEEN 2 WEEKS
TO 2 MONTHS
ZDV(D4T)+3TC+EFV
Page 59

60. CDC GUIDELINE
For patients with a CD4+ count <100/cc, ART should be started
after >2 weeks of TB treatment to reduce confusion about
overlapping toxicities, drug interactions, and the occurrence of
paradoxical reactions or IRIS.
• For persons with a CD4+ count of 100–200/cc,delay ART until
the end of the 2-month intensive phase of anti-TB treatment.
• In those with a sustained CD4+ count 200-350/cc, ART could
be started during the anti-TB maintenance phase.
Page 60

61. renal failure and severe renal insuffciency
RIF and INH are metabolized by the liver, so
conventional dosing may be used in the setting of renal
insufficiency
PZA is also metabolized by the liver but its metabolites
may accumulate in patients with renal insufficiency
EMB is about 80% cleared by the kidneys and may
accumulate in patients with renal insufficiency
Page 61
MMWR 2003;52:63-64

62. Decrease dose or increasing the dosing interval ?
• Decreasing the dose of selected antituberculosis drugs
may not be the best method of treating tuberculosis
because,although toxicity may be avoided, the peak
serum concentrations may be too low.
• Therefore increasing the dosing interval of pyrazinamide
and ethambutol are recommended and doses should be
adjusted Three times per week
Page 62
MMWR 2003;52:63-64

63. Page 63
MMWR 2003;52:63-64

64. pregnancy and breastfeeding
A pregnant woman
The first line anti-TB drugs are safe for use in pregnancy With the
exception of streptomycin, streptomycin is ototoxic to the fetus and
should not be used during pregnancy.
A breastfeeding woman
should receive a full course of TB treatment. Timely and properly
applied chemotherapy is the best way to prevent transmission to the
baby. After active TB in the baby is ruled out, the baby should be
given 6 months of isoniazid preventive therapy,
Pyridoxine supplementation is recommended for all pregnant or
breastfeeding women taking isoniazid
Page 64

65. LIVER DISEASE
If the serum alanine aminotransferase level is more than 3 times
normal before the initiation of treatment,1 of the following regimens
should be considered :
• Two hepatotoxic drugs (rather than the three in the standard
regimen):
— 9 HRE
— 2 HRSE followed by 6 HR
— 6–9 RZE
• One hepatotoxic drug:
— 2 HES followed by 10 HE
• No hepatotoxic drugs:
— 18–24 months of streptomycin, ethambutol and a fluoroquinolone.
Page 65

66. .
THANK YOU
Page 66