1. TUBERCULOSIS REGIMEN:
DOTS/WHO AND INDIAN
GUIDELINES
DR PRATYUSH KUMAR
MODERATOR :- Dr. UJJWAL
PAREKH

2. Epidemilogy

3. Definition
• New A TB patient who has never had
treatment for TB or has taken anti-TB drugs
for less than one month
• Relapse A TB patient who was declared
cured or treatment completed by a physician
and who reports back to the health facility
and is now found to be sputum smear-
positive
• Treatment after default: A patient, who has
received treatment for TB for a month or
more from any source and returns for
treatment after having defaulted i.e., not
taken anti-TB drugs consecutively for two

4. • Treatment failure Any TB patient who is
smear-positive at 5 months or more after
initiation of treatment
• Defaulted A Patient after treatment
initiation has interrupted treatment
consecutively for >2 months

5. Case definitions - WHO
• Tuberculous intrathoracic
lymphadenopathy (mediastinal and/or
hilar) or tuberculous pleural effusion,
without radiographic abnormalities in the
lungs, constitutes a case of
extrapulmonary TB
• A patient with both pulmonary and
extrapulmonary TB should be classified as
a case of pulmonary TB.
• The case definition of an EPTB case with
several sites affected depends on the site

8. AFB on ZN stain

9. New patients
• Presumed to have drug-susceptible TB with
two exceptions:
– Where there is a high prevalence of isoniazid
resistance in new patients or
– If they have developed active TB after known
contact with a patient documented to have drug-
resistant TB; they are likely to have a similar drug
resistance pattern to the source case and DST
should be carried out at the start of treatment.
• While DST results of the patient are awaited,
a regimen based on the DST of the
presumed source case should be started.

10. DOTS TB regimen
• For all “new” pulmonary (smear positive and
negative), extra-pulmonary and other TB patients
regimen is: 2 H3R3Z3E3 / 4H3R3.
• All “relapses, treatment after default, failures and
others” are treated with the regimen for previously-
treated cases: 2S3H3R3Z3E3 /1 H3R3Z3E3 / H3R3E3.
• The PWB has a color code indicating the two
regimens—red for “new”, blue for “previously
treated”

11. Regimens for previously treated patients

12. Non-DOTS Treatment Regimen
under RNTCP
• Treatment regimen of 12-month duration
comprising 2 months of she and 10
months of he (2 SHE/10 HE).
• Adverse reactions to rifampicin and/or
pyrazinamide

13. • Revised National Tuberculosis Control
Program uses short course chemotherapy
given intermittently—thrice weekly under
direct observation (DOTS) for both
pulmonary and extra-pulmonary
tuberculosis patients.

14. INTRODUCTION

15. WHO guidelines
• Wherever feasible, the optimal dosing
frequency for new patients with pulmonary
TB is daily throughout the course of therapy
• New patients with pulmonary TB may receive
a daily intensive phase followed by three
times weekly continuation phase
[2HRZE/4(HR)3 ] provided that each dose is
directly observed
• 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

16. Follow up
• If the sputum smear is positive after 2 months
of treatment, the IP of four drugs (H, R, Z and
E) is continued for another 1 month
• sputum examined after the completion of the
extension of IP. Irrespective of the sputum
results after this extension of the IP, 4 months
of the CP is started.
• If the sputum smear is positive after 5 or
more months of treatment, the patient is
declared as a “Failure” and is placed on the
“Previously Treated” treatment regimen
afresh

17. Co-existent TB and diabetes
• Hospitalization in patients with poor
diabetic control
• Ideally insulin should be used
• Maintain fasting blood sugar<100 mg %
and glycosylated HB <6%
• Use of potentially neuropathic agents in
patients with peripheral neuropathy
demands special consideration and
administration of pyridoxine

18. Definitions
• MDR-TB is defined as tuberculosis disease where the
bacilli is resistant to isoniazid (H) and rifampicin (R),
with or without resistance to other drugs
• 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
fluoroquinolones and any one of the second-line
injectable drugs (namely Kanamycin, Capreomycin or
Amikacin)
• Totally Drug–Resistant Tuberculosis (TDR-TB) TB
strains that showed in-vitro resistance to all first and
second line drugs tested (isoniazid, rifampicin,
streptomycin, ethambutol, pyrazinamide, ethionamide,
para-aminosalicylic acid, cycloserine, ofloxacin,

19. Who - data
• At the global level, 15% of previously
treated patients have MDR
• MDR to be 32% in patients returning after
defaulting or relapsing and significantly
higher (49%) in patients whose prior
treatment has failed

20. Multidrug Resistant TB and DOTS-
Plus
• Prevention of MDR-TB is given priority under
RNTCP rather than its treatment
• The following are the criteria to label a patient as
MDR-TB suspect.
• A new smear-positive patient remaining smear-
positive at the end of fifth month.
• A new smear-negative patient becoming smear-
positive at the end of fifth month.
• A patient treated with regimen for previously
treated remaining positive at fourth month
• Smear-positive contacts of an
established/confirmed MDR-TB case

21. RNTCP MDR-TB Treatment
Regimen
The
• Diagnosis of MDR-TB should be done
through culture and drug susceptibility
testing
• 6 drugs(kanamycin [km], levofloxacin(lvx),
ethionamide [eto], pyrazinamide [Z],
ethambutol [E] and cycloserine [cs]) during
6-9 months of an intensive phase
• 4 drugs (lvx, eto, E and cs) during the 18
months of the continuation phase

23. Dosages of drugs are based upon
three weight bands

24. Treatment regime
• All drugs should be given in a single daily dosage
under DOT by a DOT Provider
• On the 7th day (Sunday), the oral drugs will be
administered unsupervised and kanamycin will be
omitted
• If intolerance occurs to the drugs, ethionamide,
cycloserine and PAS may be split into two
dosages
• Intensive Phase (IP) should be given at least 6
months. It is extended up to seven/eight/nine
months in patients who have a positive culture
result taken in fourth/fifth/sixth month of treatment
correspondingly. Continuation Phase (CP) is given

25. Follow-up Schedule (RNTCP)
• Smear examination should be conducted
monthly during the IP
• at least quarterly during the CP
• Culture examination should be done at
least at 4, 6, 12, 18 and 24 months

26. Monitoring the MDR-TB patient
(who)
• sputum smears and cultures should be
performed monthly until smear and culture
conversion
• Conversion is defined as two consecutive
negative smears and cultures taken 30
days apart
• After conversion, the minimum frequency
recommended for bacteriological
monitoring is monthly for smears and
quarterly for cultures.

27. Symptom-based approach to side
effects of anti-TB drugs
Symptom Drug Management
Gastrointestinal
(vomiting or
epigastric
discomfort)
Any oral
medication
Maintain hydration
Consider treatment with antiemetics
(e.g. domperidone)
and proton pump inhibitors (eg.
Omeprazole)
Itching/Rashes Isoniazid (and
other drugs
also)
Itching without rash or a mild rash
Continue treatment antihistamines
Itching with moderate to severe rash
Stop all drugs till symptoms subside
Treat with antihistamines
Patients with mucosal involvement, fever and
hypotension will requiretreatment with corticosteroids
When the reaction subsides reintroduce drugs one-
by-one in this order
1. INH. 2. Rifa. 3. Pyra. 4. Etham
Re-introduce each drug in a small dose and gradually
increase over 3 days before introducing the next

28. Tingling/
burning/
numbness in
the
hands and feet
Isoniazid Give pyridoxine 100 mg/day orally
or parenterally until symptoms subside.
Patients not responding to pyridoxine will
require treatment with amitryptiline
Joint pains Pyrazinamid
e
Give NSAIDs like paracetamol, Aspirin or
Ibuprofen and in severe cases Indomethacin for a
week to 10 days
In severe cases, estimate serum uric acid levels
If uric acid levels are significantly raised, treat
with NSAIDs and colchicine. Allopurinol is not
effective.
In severe cases with normal or slightly elevated
uric acid, consider reduction of the dose of
Pyrazinamide.
Impaired vision Ethambutol Impaired vision usually returns to normal within a
few weeks of stopping ethambutol.
Ringing in the
ears, Loss
of hearing,
dizziness and
loss of balance
Streptomycin As hearing loss is usually not reversible, do not
restart Streptomycin

29. Hepatitis:
Anorexia
nausea
/Vomiting/
Jaundice
Isoniazid,
Rifampicin
or
Pyrazinamid
e
Rule out other causes of hepatitis
Do not restart treatment till symptoms
resolve and liver enzymes return to
baseline levels
If liver enzymes cannot be performed, wait
for 2 weeks after jaundice has disappeared
to
restart treatment
Restart treatment with one drug at a time
starting with 1. INH 2. Pyra 3. Rifa
In patients with severe disease in whom
treatment cannot be stopped, use a non
hepatotoxic regimen consisting of
Streptomycin and Ethambutol

30. Management of drug-induced
hepatitis
• 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; and
— the capacity of the health unit to manage
the side-effects of TB treatment

31. • If it is thought that the liver disease is
caused by the anti-TB drugs, 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
fluoroquinolone should be started.

32. • wait for liver function tests to revert to
normal and clinical symptoms (nausea,
abdominal pain) to resolve before
reintroducing the anti-TB drugs
• drugs are reintroduced one at a time
• If symptoms recur or liver function tests
become abnormal, the last drug added
should be stopped

33. • starting with rifampicin because it is less
likely than isoniazid or pyrazinamide to
cause hepatotoxicity and is the most
effective agent
• After 3–7 days, isoniazid may be
reintroduced
• patients who have experienced jaundice
but tolerate the reintroduction of rifampicin
and isoniazid, it is advisable to avoid
pyrazinamide

34. • If rifampicin is implicated, a suggested
regimen without rifampicin is 2 months of
isoniazid, ethambutol and streptomycin
followed by 10 months of isoniazid and
ethambutol.
• If isoniazid cannot be used, 6–9 months of
rifampicin, pyrazinamide and ethambutol can
be considered.
• If pyrazinamide is discontinued 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, the non-hepatotoxic regimen consisting
of streptomycin, ethambutol and a

35. Co-management of HIV and active
TB disease
• Three I’s for reducing the burden of TB in
persons living with HIV: Intensified case-
finding (ICF), Isoniazid preventive
therapy (IPT) and TB Infection control
(IC) for people living with HIV
• WHO recommends HIV testing for patients
of all ages who present with signs or
symptoms that suggest tuberculosis

36. Recommendation
• receive daily TB treatment at least during the
intensive phase
• For the continuation phase, the optimal
dosing frequency is also daily
• three times weekly dosing during the
continuation phase is an acceptable
alternative
• TB patients who are living with HIV should
receive at least the same duration of TB
treatment as HIV-negative TB patients
• Co-trimoxazole preventive therapy

37. Antiretroviral therapy
• 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

38. Art regimen
• two nucleoside reverse transcriptase
inhibitors (NRTIs) plus one non-nucleoside
reverse transcriptase inhibitor (NNRTI)
• NRTI backbone is zidovudine (AZT) or
tenofovir disoproxil fumarate (TDF),
combined with either lamivudine (3TC) or
emtricitabine (FTC). For the NNRTI, WHO
recommends either efavirenz (EFV) or
nevirapine (NVP)
• recommended first-line ART regimens for TB
patients are those that contain efavirenz
(EFV)

39. • ART regimen containing a boosted protease
inhibitor (PI), it is recommended to give a
rifabutin-based TB treatment.
• If rifabutin is not available, the use of
rifampicin and a boosted antiretroviral
regimen containing lopinavir or saquinavir
with additional ritonavir dosing is
recommended
• dosage of Rifabutin during the administration
of second line ART regimen containing LPV/r
shall be 150 mg Rifabutin, dosed thrice-
weekly for all patients>30 kg weight.

40. Complications
• Mild to moderate IRIS is relatively common
• reported in up to one-third of patients
• present as fever, enlarging lymph nodes,
worsening pulmonary infiltrates, or
exacerbation of inflammatory changes at
other sites
• presents within 3 months of the start of ART
• more common when CD4 cell count is low
(<50 cells/mm3)
• Most cases resolve without intervention and
ART can be safely continued
• IRIS is a diagnosis of exclusion.

41. Monitoring drug treatment
• smear microscopy may be performed at completion of
the intensive phase .
• Smear status at the end of the intensive phase is a
poor predictor of which new patients will relapse
– therapy was poorly supervised and poor patient adherence
– poor quality of anti-TB drugs
– Doses below the recommended range;
– resolution is slow because the patient had extensive
cavitation and a heavy initial bacillary load;
– co-morbid conditions interfering with adherence or with
response
– drug-resistant M. tuberculosis that is not responding to
first-line treatment;
– non-viable bacteria remain visible by microscopy

42. • It is unnecessary, unreliable and wasteful of
resources to monitor the patient by chest
radiography
• specimen obtained at the end of the intensive
phase (month 2) is smear-positive, sputum
smear microscopy should be obtained at the
end of the third month
• at the end of month 3 is smear-positive,
sputum culture and drug susceptibility testing
(DST) should be performed
• pulmonary smear-negative disease and
extrapulmonary TB the weight of the patient

43. Definitions of treatment
outcomes

45. Treatment of extra pulmonary
TB
• Pulmonary and extrapulmonary disease
should be treated with the same regimens
• some experts recommend 9–12 months of
treatment for TB meningitis
• 9 months of treatment for TB of bones or
joints
• adjuvant corticosteroid treatment is
recommended for TB meningitis and
pericarditis
• In tuberculous meningitis, ethambutol should
be replaced by streptomycin

46. Treatment regimens in special
situations
• Pregnancy :-
– streptomycin is ototoxic to the fetus and should
not be used during pregnancy
• Lactation:-
– Mother and baby should stay together and the
baby should continue to breastfeed.
– After active TB in the baby is ruled out, the baby
should be given 6 months of isoniazid preventive
therapy, followed by BCG vaccination
• Women on OCPs :-
– increase OCP dose, or choose alternative
contraception

47. Liver disorders
• If the serum alanine aminotransferase level is more than 3
times normal
• Possible regimens include:
Two hepatotoxic drugs (rather than the three in the standard
regimen):
— 9 months of isoniazid and rifampicin, plus ethambutol (until or
unless isoniazid susceptibility is documented);
— 2 months of isoniazid, rifampicin, streptomycin and
ethambutol, followed by 6 months of isoniazid and rifampicin;
— 6–9 months of rifampicin, pyrazinamide and ethambutol.
One hepatotoxic drug:
— 2 months of isoniazid, ethambutol and streptomycin, followed
by 10 months of isoniazid and ethambutol.
No hepatotoxic drugs:
— 18–24 months of streptomycin, ethambutol and a
fluoroquinolone.

48. Renal failure
• Isoniazid and rifampicin are eliminated by
biliary excretion
• significant renal excretion of ethambutol
and metabolites of pyrazinamide
• Three times per week administration:
pyrazinamide (25 mg/kg), and ethambutol
(15 mg/kg)
• if streptomycin must be used, the dosage
is 15 mg/kg, two or three times per week