Tuberculosis remains a major global infectious disease threat. It is caused by the bacterium Mycobacterium tuberculosis, which is spread through airborne droplets. Latent TB infection occurs when a person is infected by TB bacteria but does not have active disease. Active TB disease may develop when bacteria become active in the body and cause pulmonary or extrapulmonary disease. Diagnosis involves tests such as the Mantoux test, sputum smear, and chest x-ray. Treatment requires a multi-drug regimen over a period of 6-24 months to prevent drug resistance.
Tuberculosis remains a major global infectious disease threat. It is caused by the bacterium Mycobacterium tuberculosis, which is spread through airborne droplets. Latent TB infection occurs when a person is infected by TB bacteria but does not have active disease. Active TB disease may develop when bacteria become active in the body and cause pulmonary or extrapulmonary disease. Diagnosis involves tests such as the Mantoux test, sputum smear, and chest x-ray. Treatment requires a multi-drug regimen over a period of 6-24 months to prevent drug resistance.
Tuberculosis remains a major global infectious disease threat. It is caused by the bacterium Mycobacterium tuberculosis, which is spread through airborne droplets. Latent TB infection occurs when a person is infected by TB bacteria but does not have active disease. Active TB disease may develop when bacteria become active in the body and cause pulmonary or extrapulmonary disease. Diagnosis involves tests such as the Mantoux test, sputum smear, and chest x-ray. Treatment requires a multi-drug regimen over a period of 6-24 months to prevent drug resistance.
Tuberculosis remains a major global infectious disease threat. It is caused by the bacterium Mycobacterium tuberculosis, which is spread through airborne droplets. Latent TB infection occurs when a person is infected by TB bacteria but does not have active disease. Active TB disease may develop when bacteria become active in the body and cause pulmonary or extrapulmonary disease. Diagnosis involves tests such as the Mantoux test, sputum smear, and chest x-ray. Treatment requires a multi-drug regimen over a period of 6-24 months to prevent drug resistance.
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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
& 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)
