For BSc Nursing students 1st year, under KU curriculum

1. Regimens, prophylaxis of TB
and DOTS for BSc Nursing,
KU curriculum
Dr. Jessica Dali
Department of Pharmacology

3. • Bacteriologically confirmed case of TB: A patient from whom a
biological specimen is positive by smear microscopy, culture or WHO-
approved rapid diagnostic test (such as Xpert MTB/RIF). All such cases
should be notified, regardless of whether TB treatment is started.
• Clinically diagnosed case of TB: A patient who does not fulfil the
criteria for bacteriologically confirmed TB but has been diagnosed
with active TB by a clinician or other medical practitioner who has
decided to give the patient a full course of TB treatment. (Diagnosed
on the basis of X-ray abnormalities or suggestive histology and extra
pulmonary cases without laboratory confirmation.)

4. • Cured: A pulmonary TB patient with bacteriologically-confirmed TB at the
beginning of treatment who was smear- or culture- negative in the last month of
treatment and on at least one previous occasion.
• Completed treatment: A TB patient who completed treatment without evidence
of failure but with no record to show that sputum smear or culture results in the
last month of treatment and on at least one previous occasion were negative,
either because tests were not done or because results are unavailable.
• Died: A TB patient who died from any cause during treatment.
• Failed: A TB patient whose sputum smear or culture is positive at month five or
later during treatment.
• Lost to follow-up: A TB patient who did not start treatment or whose treatment
was interrupted for two consecutive months or more.
• Not evaluated: A TB patient for whom no treatment outcome is assigned. This
includes cases ‘transferred out’ to another treatment unit as well as cases for
whom the treatment outcome is unknown to the reporting unit.
• Successfully treated: A patient who was cured or who completed treatment.

5. Case of pulmonary TB: Any bacteriologically confirmed or clinically diagnosed case
of TB involving the lung parenchyma or the tracheobronchial tree.
Case of extra pulmonary TB: Any bacteriologically confirmed or clinically diagnosed
case of TB involving organs other than the lungs, e.g. abdomen, genitourinary tract,
joints and bones, lymph nodes, meninges, pleura, skin.
New case of TB: A patient who has never been treated for TB or has taken anti-TB
drugs for less than one month.
Retreatment case of TB: A patient who has been treated for one month or more
with anti-TB drugs in the past. Retreatment cases are further classified by the
outcome of their most recent course of treatment into four categories.
1. Relapse patients have previously been treated for TB, were declared cured or
treatment completed at the end of their most recent course of treatment, and are
now diagnosed with a recurrent episode of TB (either a true relapse or a new
episode of TB caused by reinfection).
2. Treatment after failure patients have previously been treated for TB and their
most recent course of treatment failed i.e. they had a positive sputum smear or
culture result at month 5 or later during treatment.
3. Treatment after loss to follow-up patients have previously been treated for TB
and were declared ‘lost to follow-up’ at the end of their most recent course of
treatment.

6. • Case of multidrug-resistant TB (MDR-TB): TB resistant to two first-
line drugs: isoniazid and rifampicin. For most patients diagnosed with
MDR-TB, WHO recommends treatment for 20 months with a regimen
that includes second- line anti-TB drugs.
• Case of rifampicin-resistant TB (RR-TB): A patient with TB that is
resistant to rifampicin detected using phenotypic or genotypic
methods, with or without resistance to other anti-TB drugs. It
includes any resistance to rifampicin, whether mono-resistance,
multidrug resistance, poly-drug resistance or extensive drug
resistance.

7. DOTS
• Single daily dose of all first line anti-TB drugs is preferred for TB. The
“directly observed treatment short course” (DOTS) was
recommended by WHO in 1995.
• Response is fast in the first few weeks as the fast dividing bacilli are
eliminating rapidly. Symptomatic relief is evident within 2-4 weeks.
• All regimens have an initial intensive phase lasting 2-3 months, aimed
to kill the bacilli rapidly to bring about sputum conversion and afford
symptomatic relief. This is followed by a continuation phase lasting 4-
6 months during which the remaining bacilli are eliminated so that
the relapse doesn’t occur.

8. • Drug- resistant TB: resistant to one first line anti-TB drug, either INH
or R
• MDR TB: resistant to INH and R, possibly additional agents
• XDR TB( Extensively Drug resistant TB) :resistant to INH, R, FQ, and
either Aminoglycosides or capreomycin or both

9. Anti-tubercular Drugs
• First line- Isoniazid, Rifampicin, Pyrazinamide, Ethambutol,
Streptomycin
• Second line- FQs- Moxifloxacin, Levofloxacin, Injectable drugs like-
Kanamycin, Amikacin, Capreomycin

10. Isoniazid (INH)
• Fast multiplying organisms are rapidly killed; bactericidal
• Inhibits the synthesis of mycolic acid present in the mycobacterial cell
wall
• About 1 in 106 bacilli resistant to INH. If given alone, these bacteria
proliferate causing resistance
• Interactions :
• retards Phenytoin, Carbamazepine, Warfarin metabolism
• Aluminium hydroxide inhibits INH absorption

11. Isoniazid (INH)
• Adverse Effects
• Peripheral neuritis due to interference with Pyridoxine metabolism.
Hence, Pyridoxine given prophylactically 10 mg/day prevents
neurotoxicity
• Hepatitis

12. Rifampicin (R)
• Bactericidal drug that interrupts RNA synthesis by binding to DNA
dependent RNA polymerase and blocking its polymerizing function
• Interactions
• Microsomal enzyme inducer, enhances metabolism of many drugs
including itself, e.g. Warfarin, Theophylline, Phenytoin, Oral
contraceptive-failure
• Adverse Effects: HEPATITIS, Urine and mucous membrane become
orange-red

13. Rifampicin also used in
• Leprosy
• Prophylaxis of Meningococcal and H. influenza meningitis and carrier
state

14. Pyrazinamide (Z)
• Tuberculocidal
• Mechanism not well known, is converted inside the mycobacterial cell
into an active metabolite pyrazinoic acid and inhibits mycolic acid
synthesis
• Well penetrated in CSF- useful in meningeal TB
Adverse effects
• Hepatotoxicity
• Hyperuricemia- gout can occur

15. Ethambutol (E)
• Hastens the rate of sputum conversion, helps to prevent resistance
• Mechanism of action not fully understood. Found to interfere with
mycolic acid incorporation in the mycobacterial wall.
• Penetrates meninges inconsistently, when they are inflamed
• Adverse effects:
• Loss of visual acquity /color vision, field defects due to retro bulbar
neuritis- most important dose and duration of therapy dependent
toxicity
• Hyperuricemia/Gouty arthritis

16. Streptomycin (S)
• First clinically useful drug
• Poorly acts on extracellular bacilli
• Penetrates tubercular cavities, does not cross CSF
• Resistance against it worldwide
• IM injection, lower margin of safety
Adverse effects
• Ototoxic, nephrotoxic, Neuromuscular blockade

17. Category wise treatment for TB
TB category Initial phase(daily) Continuation
Phase
Total duration
I 2HRZE(S) 4HR
or 6HE
6
8
II 2HRZES+ 1 HRZE 5HRE 8
III 2HRZ 4HR
or 6HE
6
8
IV Chronic case
H-Isoniazid
R-Rifampcin
Z-Pyrazinamide
E-Ethambutol
S-Streptomycin

19. Category I patients
• New (untreated) smear positive pulmonary TB patients
• New smear negative pulmonary TB with extensive parenchymal
involvement
• New cases of severe forms of extra pulmonary TB, e.g. meningitis,
military, pericarditis, peritonitis, bilateral or extensive pleural effusion,
spinal, intestinal, genitourinary TB

20. Category II patients
• Treatment failure: A patient who remains or again becomes smear
positive 5 months or later after commencing treatment. Also one who
was smear negative at start of therapy and becomes smear positive
after the 2nd month
• Relapse: A patient declared cured from any form of TB in the past
after receiving one full course of chemotherapy and now has become
sputum positive
• Treatment after interruption or default: A patient who interrupts
treatment for 2 months or more and returns with sputum positive or
clinically active TB

21. Category III patients
• New cases of smear negative pulmonary TB with limited parenchymal
involvement or less severe forms of extra pulmonary TB, i.e. lymph
node, unilateral pleural effusion, bone excluding spine, peripheral
joint or skin TB

22. Category IV
• Chronic cases who have remained or have become smear positive
after completing fully supervised retreatment (Cat II regimen).
• They are most likely MDR cases.
• MDR TB is defined as resistance to both H and R and may be any
number of other anti-TB drugs. MDR-TB has a more rapid course
(some die in 4-16 weeks)

23. • TB in pregnant women
• Standard 6 month regimen 2 HRZ+4HR should be given. E can be
given during late but not early pregnancy. S can cause permanent
deafness in pregnancy.
• TB in breastfeeding women
• All anti TB drugs are compatible with breast feeding; full course
should be given to the mother, but the baby should be watched.
• The infant should receive BCG vaccination and isoniazid prophylaxis
• TB during contraception
• Rifampicin causes OCP failure. Either change the mode of
contraception or increase estrogen dose to 50 mcg

24. Chemoprophylaxis of TB
• Indications
• Contacts of open cases who show recent Mantoux conversion
• Children with positive Mantoux and a TB patient in the family
• Neonate of TB mother
• Patients of leukemia, diabetes, silicosis or those who are HIV positive
but are not anergic, or are on corticosteroid therapy who show a
positive Mantoux
• Patients with an old inactive disease who are assessed to have
received inadequate therapy

25. Drug used for prophylaxis
• Isoniazid 300 mg (10 mg/kg in children) daily for 6-12 months
• Now because of high incidence of H resistance, a combination of H (5
mg/kg) and R (10 mg/kg) given for 6 months is preferred.

26. TB in AIDS patients
• The initial 2HRZE phase is followed by a continuous phase of HR for 7
months ( total 9 months).Alternately 3 drugs HRE are used for 4
months in the continuation phase.