TUBERCULOSIS

Dr.Sadaf farooqui
 TUBERCULOSIS
 TB remains a leading infectious killer globally.
 1/3 of the world’s population currently is infected &
drug resistance is increasing in many areas.
 Risk factors for infection: location & place of birth; race,
ethnicity & gender; co-infection with HIV.
 Etiology: M. tuberculosis. Grow slowly, doubling time 20
h.
 Transmission: droplet infection (person to person);
coughing or sneezing.
 PATHOPHYSIOLOGY
 Primary infection: by inhaling droplet nuclei that
containing M. tuberculosis.
 Progression to clinical disease depends on: number of
organism (infection dose), virulence, host cell-
mediated immune response. It infects the posterior
apical region of the lungs.
 Infection ► T-cell activation & secreting INF-gamma
& cytokines stimulating macrophages to form
granuloma ► +ve Mantoux test.
 Reactivation of the disease ► Inflammation ►
Granuloma.
TYPES
 Pulmonary
 Extra-Pulmonary

 Miliary (Widely disseminated)

 SYMPTOMS: wt loss, fatigue, productive cough, fever

& night sweats.
 Diagnosis: Dullness to chest percussion, rales
(abnormal sounds like bubbling or crackling).
 Lab:▲no. of Lymphocytes (predominance of
lymphocytes)
DIAGNOSIS
 Mantoux test
 Tuberculin is a glycerol extract of the tubercle bacillus. Purified protein
derivative (PPD) tuberculin is a precipitate of species-nonspecific
molecules obtained from filtrates of sterilized, concentrated cultures.
 Sputum

 Bronchoscopy
( 2 smears are
Negative)

 Chest Radiograph

 Biopsy for those with extra-pulmonary TB

 Blood culture are +ve with AIDS patients.
 TREATMENT OF TB: GENERAL APPROACH
LTBI (Latent Tuberculosis Infection in ACTIVE TB
Adults)

Not have active tb & +ve skin Disease present

test.
Monotherapy 2 & generally 3 or 4 drugs must be used
simultaneously.
Isoniazid, Rifampicin The shortest duration of treatment generally is 6
months & 2 to 3 years of treatment in the
presence of MDR

Nonpharmacological therapy: prevent spread, find where already spread, replenish well-
being, public health, surgery to remove destroyed lung tissue.

Directly Observed Therapy (DOT)

The practice of a health care provider or other responsible person observing as the patient ingests
and swallows the TB medications.
Purpose:
 ensure adherence to TB therapy
 reduce the risk of developing drug resistance
 reduces the risk to the community.
 observe the patient for any apparent toxicities.
 A person with latent TB infection
•Usually has a skin test or blood test result indicating TB infection
•Has a normal chest x-ray and a negative sputum test
•Has TB bacteria in his/her body that are alive, but inactive
•Does not feel sick
•Cannot spread TB bacteria to others
•Needs treatment for latent TB infection to prevent TB disease; however, if
exposed and infected by a person with multidrug-resistant TB (MDR TB) or
extensively drug-resistant TB (XDR TB), preventive treatment may not be an
option
 LATENT TUBERCULOSIS INFECTION TREATMENT
 Isoniazid is the preferred drug for treating latent TB infection. Generally, isoniazid alone is
given for 9 months.
 The keys to successful treatment of LTBI are

infection by an isoniazid-susceptible isolate

adherence to the 9-month regimen,

and no exogenous reinfection

 Isoniazid adult doses are usually 300 mg daily (5–10 mg/kg of body weight)
 When adherence is an issue, twice-weekly isoniazid (900 mg in an adult) can be given using
DOT.
 Pregnant women, alcoholics ,and patients with poor diets who are treated with isoniazid should
receive pyridoxine (vitamin B6) 10–50 mg daily to reduce the incidence of central nervous
system (CNS) effects or peripheral neuropathies.
 Rifampin 600 mg daily for 4 months can be used when isoniazid resistance is suspected or
when the patient cannot tolerate isoniazid.
PHARMACOLOGICAL THERAPY
TREATING LTBI
 STANDARD TREATMENT OF TB
 INH + RIF + PZA+ EMB ►FOR 2 month. FOLLOWED
BY INH + RIF FOR 4 month.
 Patients with cavitation ► 9 months INH+ RIF.

 Doses missed during an intermittent TB regimen

decrease its efficacy & ▲ relapse rate.
 It is critical to avoid monotherapy & it is critical
to avoid adding a single drug to a failing regimen.
 CNS TB requires longer treatment period 9-12 months
instead of 6 months.
 Extrapulmonary TB of soft tissues treated with
conventional therapy.
 TB of bone treated for 9 months + surgical debridement.

 Pregnant women INH+RIF+EMB

 Streptomycin, ethionamide, PASA,

 Quinolones are avoided in pregnancy as well as

nursing.
 intermitted regimens (Once & twice weekly) not
recommended for HIV- +ve patients.
 DRUG REGIMENS FOR CULTURE-POSITIVE PULMONARY
TUBERCULOSIS CAUSED BY DRUG-SUSCEPTIBLE ORGANISMS

 Each regimen has an initial phase of 2 months followed by a choice of several

options for the continuation phase of either 4 or 7 months.
 Initial phases are denoted by a number (1, 2, 3, or 4)

Continuation phases that relate to the initial phase are denoted by the number plus a
letter designation (a, b, or c).
 Because of the relatively high proportion of adult patients with tuberculosis caused by
organisms that are resistant to isoniazid, four drugs are necessary in the initial
phase for the 6-month regimen to be maximally effective.
 Thus, in most circumstances, the treatment regimen for all adults with previously
untreated tuberculosis should consist of a 2-month initial phase of isoniazid (INH),
rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB). (Table43__2,
Regimens1–3).
 For children whose visual acuity cannot be monitored, EMB is usually not
recommended except when there is an increased likelihood of the disease
being caused by INH-resistant organisms (Table 6) or when the child has
“adult-type” (upper lobe infiltration, cavity formation) tuberculosis.
 If PZA cannot be included in the initial phase of treatment, or if the isolate is
resistant to PZA alone (an unusual circumstance), the initial phase should
consist of INH, RIF, and EMB given daily for 2 months (Regimen 4).
Examples of circumstances in which PZA may be withheld include severe
liver disease, gout, and, perhaps, pregnancy.
 INITIAL PHASE(2 MONTH)

 Regimens1 and 4:The initial phase may be given daily

throughout
 Regimen 2: daily for 2 weeks and then twice weekly for 6
weeks
 Regimen 3: Three times weekly throughout.
 For patients receiving daily therapy, EMB can be discontinued
as soon as the results of drug susceptibility studies demonstrate
that the isolate is susceptible to INH and RIF.
 CONTINUATION PHASE (4-7MONTH)
 The 4-month continuation phase should be used in the large majority of
patients.
 The 7-month continuation phase is recommended only for three groups:
a) patients with cavitary pulmonary tuberculosis caused by drugs
susceptible organisms and whose sputum culture obtained at the time
of completion of 2 months of treatment is positive;
b) patients whose initial phase of treatment did not include PZA;
c)patients being treated with once weekly INH and rifapentine and
whose sputum culture obtained at the time of completion of the initial phase
is positive.
o The continuation phase may be given daily (Regimens 1a and 4a), two times
weekly by DOT (Regimens 1b, 2a, and 4b), or three times weekly by DOT
(Regimen 3a).
 TB+ HIV
 For human immunodeficiency virus (HIV)-seronegative patients with non cavitary
pulmonary tuberculosis (as determined by standard chest radiography),and negative
sputum smears at completion of 2 months of treatment, the continuation phase may
consist of rifapentine and INH given once weekly for 4 months by DOT (Regimens 1c
and 2b).
 If the culture at completion of the initial phase of treatment is positive, the once weekly
INH and rifapentine continuation phase should be extended to 7 months.
 All of the 6-month regimens, except the INH–rifapentine once weekly continuation
phase for persons with HIV infection (Rating EI), are rated as AI or AII, or BI or BII, in
both HIV-infected and uninfected patients.
 TB+ HIV(MAC)
 The once-weekly continuation phase is contraindicated (Rating EI) in patients with HIV
infection because of an unacceptable rate of failure/relapse, often with rifamycin
resistant organisms.
 For the same reason twice weekly treatment, either as part of the initial phase (Regimen
2) or continuation phase (Regimens 1b and 2a), is not recommended for HIV-infected
patients with CD4+ cell counts <100 cells/μl. These patients should receive either daily
(initial phase) or three times weekly (continuation phase) treatment.
 Regimen 4 (and 4a/4b), a 9-month regimen, is rated CI for patients without HIV
infection and CII for those with HIV infection.
SPECIAL CONDITIONS
 Renal failure: Dose modification for PZA & EMB (3
times weekly) as well as aminoglycosides (TDM is a
must) BUT not recommended for INH & RIF.
 Hepatic failure: ▲ liver transaminases are not
correlated with liver capacity for drug metabolism .So
these markers cannot be used as guides for drug dosing.
“Liver sparing” regimen may be used, at least
temporarily. It consists of streptomycin, levofloxacin,
and ethambutol.
 RETROBULLAR VESTIBULAR TESTING/AUDIOGRAM
NEURITIS/ VISUAL (STREPTOMYCIN)
ACUITY TEST
(ETHAMBUTOL)