Treatment of Tuberculosis

Short course chemotherapy

SCC recognized by WHO as the most cost effective method Aims of SCC: To cure the patient of tuberculosis To prevent death from active TB & its complications To prevent TB relapses To decrease TB transmission to others

SCC- Principles

Drugs for TB treatment can be given daily or intermittently Intermittent regimens are either bi- weekly or thrice weekly regimens Therapy is supervised or unsupervised Course divided into two phases: initial / intensive phase & continuation / maintenance phase Priority is given to sputum positive cases

Intermittent Chemotherapy

Drugs are given either twice weekly or thrice

weekly.

Rationale: Organism multiplication time is 18 hrs Lag period exhibited by Mycobacterium 24 hours maintenance of MIC not necessary. Achievement of serum peak levels of all drugs simultaneously is essential.

RNTCP terms & definitions

Smear positive pulmonary TB: TB in a patient with at least two initial sputum smears examinations positive for AFB OR One smear positive with radiographic abnormalities consistent with TB / culture positive for TB Smear negative pulmonary TB: Patient with symptoms suggestive of TB with at least three sputum smears negative for AFB OR diagnosed on basis of positive culture but negative smear for AFB

Type of cases
New case: Patient who has not received ATT or has received treatment for < one month Relapse: Patient declared cured but reports back & sputum is positive for AFB Treatment after default: Patient who receives ATT for a month or more but stops taking drugs for two months or more consecutively

Type of cases
Failure

case: Patient who is smear positive after 5 months or more after starting treatment OR patient initially smear negative but becomes smear positive during treatment Chronic case: Patient who remains smear positive after completing a retreatment regimen

Types of bacillary population

Rapidly multiplying bacilli: Those

within cavities
macrophages

Intracellular bacilli: Those within Persisters or semi dormant bacilli:

Show occasional spurts of metabolism

Dormant bacilli

Modes of action of Anti TB drugs

INH: Acts against rapidly growing bacilli. Kills 90% of bacilli in the first few weeks & reduces bacillary load Rifampicin: Acts on semi dormant bacilli or persisters PZA : Kills intracellular bacilli in an acidic environment, in the macrophages Sterilizing action: Effective on all kind of bacillary population. Rifampicin & PZA are good sterilizing agents & prevent relapses

First line chemotherapeutic drugs

Isonioazid (INH) : Synthetic bactericidal drug Inhibits mycolic acid synthesis in the cell wall Side effects are hepatotoxicity & peripheral neuropathy Absorption impaired by Aluminum Hydroxide

Rifampicin:

Macrocyclic antibiotic produced by Streptomyces

Meditarraneae

Bactericidal & inhibits DNA dependent RNA polymerase Active against persisters Absorbed better on an empty stomach Side affects- Anorexia, nausea, vomiting, abdominal pain, diarrhoea, immune mediated flu like syndrome, thrombocytopenia & ARF Increase dosage requirements of corticosteroids, OCP, oral anti coagulants, phenytoin, digitalis, cyclosporine's

Ethembutol: Bacteriostatic

Inhibits RNA arabinogalactan synthesis Side effect is retro bulbar neuritis Contra indicated in children

Streptomycin: First ATT to be discovered

Bactericidal, kills extra cellular organisms at high PH Inhibits ribosomal RNA synthesis Administered IM Side affects: Hypersensitive reactions, vestibular & oto toxicity, renal failure

Pyrazinamide :
Synthetic

pyrazine analogue of nicotinamide Bactericidal in acidic PH Acts by inhibiting nicotinic acid metabolism Adverse effect: Hepatotoxicity, arthralgia, hyperurecemia

Doses of essential Anti TB drugs

Drugs Daily (mg / kg) Thrice weekly (mg / kg) Twice weekly (mg / kg)

INH Rifampicin
PZA

5 10
25

10 10
35 15 30

15 10
50 15 45

Streptomyc 15 in Ethambutol 15

TB treatment regimens
TB TB patients category Initial phase Continuation phase
2EHRZ or 2E3H3R3Z3 4HR or 4H3R3

New

cases Seriously ill cases Severe EP TB

Relapses Treatment Defaults

sputum positive

failures

2SHERZ+1EHRZ Or 2S3E3R3H3Z3+1E3 H3R3Z3 2HRZ Or 2H3R3Z3

5HRE Or 5H3R3E3 4HR Or 4H3R3

Sputum

negative PTB Less severe EP TB

Direct Observed Therapy Short course - DOTS

Implemented

by WHO as essential strategy in TB control Enforced due to rising incidence of HIV and MDR-TB

Principles of DOTS are:

1. 2. 3.

4.
5.

Political commitment Passive case finding by sputum smear examination Continuous & uninterrupted supply of anti TB treatment System to report & monitor the outcome of treatment Compliance achieved by monitoring drug intake by health workers, community volunteers, family members or after hospitalization

Diagnosis of Pulmonary TB
Cough 3 weeks If 1 positive, X-ray and evaluation

AFB X 3

If 2/3 positive: Anti-TB Rx

If negative: Broad-spectrum antibiotic 10-14 days If symptoms persist, X-ray If consistent with TB

Anti-TB Treatment

TB treatment in special situations

Pregnant women: Streptomycin contraindicated, PZA ? Women on OCPS: Decreased efficacy due to Rifampicin. So OCP with higher estrogen dosage or alternate form of contraception used Chronic liver diseased: 2SHRE+6HR or 2SHE+10HE Renal failure: 2HRZ+6HR

Corticosteroids in TB

In drug hypersensitive reactions In some cases of TB meningitis TB pericarditis Hypoadrenalism TB laryngitis Renal TB Massive Lymph node enlargement with pressure effects Some cases of TB pleural effusion