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192 Cards in this Set
- Front
- Back
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Why are HIV pts more susceptible to TB?
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CD4+ cells that have an immune response to TB are depleted in HIV patients.
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What cytokines are involved in the host's cell mediated response?
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TNF-alpha and INF-gamma
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What is one way the TB resists host immune response?
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M. tuberculosis inhibits the fusion of lysosomes to phagosomes inside macrophages.
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How does primary infection of TB usually occur?
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inhaling airborne particles that contain M. tuberculosis
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What other ways can TB infection occur?
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ingestion and inoculation (puncture wound)
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What does the progression to clinical disease depend on?
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number of M. tuberculosis organisms inhaled
virulence of these organisms host's cell mediated immune response |
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What type of bacteria is M. tuberculosis?
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acid-fast bacilli
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How is M. tuberculosis identified?
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Ziehl Neelsen stain with carbol fuchsin
Will retain red color after acid-alcohol washes |
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How long does it take for M. tuberculosis to double?
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20 hours, compared to 30 minutes for most gram negative and gram positive bacteria
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What is the critical proportion for resistance for M. tuberculosis in the US?
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1%, anything greater and it is likely resistant
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How is M. tuberculosis transmitted from person-to-person?
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coughing or sneezing
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What form of TB can be transmitted by talking?
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laryngeal form
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Where does M. tuberculosis most commonly infect?
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posterior apical region of the lung
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What type of immunity from M. tuberculosis?
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cell-mediated immunity
large numbers of activated microbicidal macrophages surround the solid caseous tuberculous foci |
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What type of hypersensitivity reaction occurs with TB?
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delayed type hypersensitivity
through the activation and multiplication of T lymphocytes |
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When do granulomas form in TB?
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>3 weeks
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What is a granuloma in TB?
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activated macrophages accumulate around a caseous lesion and prevents further extension
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Who should be treated for latent or active TB?
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young, elderly, and IC
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In what percent of TB pts does reinfection occur?
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10%
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What is the most common site of reinfection?
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apices of the lungs
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What is the result of TB in the lungs?
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regional necrosis and structural collapse leading to a cavity in the lungs
results in hypoxia, respiratory acidosis, and eventually death |
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What are the most common forms of extrapulmonary TB?
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lymphatic and pleural
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What is miliary TB?
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massive inoculum of organisms enters the bloodstream causing a widely disseminated form of disease, can be fatal, medical emergency
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What is the largest risk factor for active TB?
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HIV
because CD4+ lymphocytes multiply in response to TB infection. HIV multiplies in these cells and selectively destroys them. This leadys to depletion of TB fishting lymphocytes |
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What should be treated first TB or HIV?
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TB
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Is the onset of TB fast or gradual?
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gradual
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Can swallowing infected sputum spread the disease to other areas of the body?
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yes
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What is the preferred TB test?
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Mantoux test
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What does the Mantoux test use?
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tuberculin purified protein derivative (PPD)
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What is different about the Mantoux test compared to the Heaf or tine test?
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it is quantitative
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How is the TB skin test given?
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standard 5-tuberculin-unit PPD dose is placed intracutaneously on the volar aspect of the forearm with a 26 or 27 gauge needle
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When should the TB test be read?
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48-72 hours
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What is the "booster effect"?
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pt initially doesn't respond to TB test, but if retested a week later tests positive
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Who usually has the "booster effect"?
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pts with past M. tuberculosis, past immunization with BCG (bacillus Calmette-Guerin) vaccine, past infection with other mycobacteria
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What type of test should healthcare workers initally have?
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two stage test. Once shown to be skin-test-negative any positive skin test later shows recent infection and requires tx
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What % of TB pts test negative with PPD skin test, why?
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20%, immune system overwhelmed
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What does QuantiFERON-TB Gold test measure?
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relase of INF-gamma in whole blood
happens in latent TB not in uninfected person |
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How long for results of QuantiFERON-TB Gold?
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hours instead of 2-3 days, no return visit needed
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When should sputum be collected to culture in suspected TB?
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in the morning for 3 days
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What should be used if pt can't expectorate to get sample?
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aerosolized hypertonic saline
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What can be used to diagnose extrapulmonary TB?
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samples of draining fluid or biopsies of infected site
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What criteria to diagnose TB if skin test 5mm?
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- HIV pts
- recent contacts of TB pts - fibrotic changes on chest radiograph consistent with prior TB - pts with organ transplants and othe immunosuppressed patients receiving>/= 15mg/day or predisone for 1 month |
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What criteria to diagnose TB if skin test >/= 10mm?
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- recent immigrants (last 5 years)
- injection drug user - high risk resident/employee - mycobacteriology lab personnel - persons with clinical conditions that place them at high risk - children younger than 4 and adolescents exposed to adults at high risk |
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What criteria to diagnose TB if skin test >/= 15mm?
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no risk factors for TB
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What conditions place a person at high risk for TB?
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silicosis, DM, chronic renal failure, hematologic disorders (leukemia, lymphomas), malignancies (carcinoma of head, neck or lungs), wt loss >/= 10% of IBW, gastrectomy, jejunoileal bypass
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How long is tx usually for TB?
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at least 6 months
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Who uses monotherapy in TB?
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infected patients who do not have active TB
minimum of 2 drugs, genrally 3-4 if active |
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How long is tx usually for multidrug resistant TB?
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2-3 years
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What is the bacillary load for asymptomatic pt?
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10^3 organisms
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What is the bacillary load for cavitary pulmonary TB?
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10^11
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What is the rate for naturally occurring mutants for the antituberculosis drugs?
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1 in 10^6 to 1 in 10^8
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Why is isoniazid monotherapy ok for monotherapy in latent infection?
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isoniazid resistant organis occurs about 1 in 10^6 organism, but only 10^3 organisms present
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What are the best drugs for preventing drug resistance in active TB?
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rifampin and isoniazid
also, ethambutol, streptomycin, and pyrazinamide |
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What are the 3 subpopulations of mycobacteria in the body?
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extracellular - rapidly dividing bacteria found in cavities (10^7 to 10^9 organisms)
group in caseating granulomas (10^5 to 10^7) - semidormant with occasional bursts of metabolic activity intracellular mycobacteria in macrophages (10^4 to 10^6) |
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What is the best tx for extracellular?
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isoniazid
also, refampin, streptomycin |
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What is best tx for granulomas?
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pyrazinamide that is converted to pyrazinoic acid by M. tuberculosis
also, rifampin and isoniazid |
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What is best tx for intracellular?
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rifampin, isoniazid, and quinolones
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Should anyone be notified of new cases of TB?
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yes, the local health department
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What are the vaccines against TB?
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BCG and M. vaccae
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Do the vaccines prevent infection by M. tuberculosis?
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no
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What is the preferred tx for latent infection?
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300mg isoniazid for 9 months
(5-10mg/kg) |
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What pt counseling should be included with isoniazid?
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give on an empty stomach
antacids should be avoided within 2 hours of dosing |
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What isoniazid dosing is available if adherance is a problem?
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900mg twice weekly dose
9 months of therapy is recommended but 6 months provides considerable benefit HIV must do 9 month therapy |
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What can be used in latent infection if pt is isoniazid resistant or does not tolerate isoniazid?
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rifampin 600mg daily for 4 months
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What can be used in latent infection if pt is at high risk for DI from rifampin?
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rifabutin 300mg daily
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Why is pyrazinamide plus rifampin combo not recommended anymore for latent infection?
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hepatotoxicity
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What should be used if pt is isoniazid and rifampin resistant in latent infection?
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no regimen proved to be effective
ethambutol plus levofloxacin might be effective |
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What should pregnant women, alcoholics, and pts with poor diets who are treated with isoniazid receive?
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pyridoxine (Vitamin B6) 10-50mg daily to reduce CNS effects or peripheral neuropathies
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How often should pts treated for latent TB be monitored?
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monthly
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What are the main antiTB drugs used for active TB?
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isoniazid and rifampin
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What is a drug-o-gram?
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shows the start and stop dates of all antimycobacterial drugs on a horizontal bar graph
should be used for retreatment patients |
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What is the standard tx for active TB?
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isoniazid, rifampin, pyrazinamide, and ethambutol for 2 months
isoniazid and rifambin for 4 months |
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When can ethambutol be stopped?
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if susceptibility to isoniazid, rifampin, and pyrazinamide is shown
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How long should rifampin and isoniazid therapy be if pyrazinamide isn't used?
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9 months
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When should pts be removed from respiratory isolation?
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when the pt sputum smears convert to negative, but should be careful because still may be able to give TB to someone
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What pts are typically slow to respond to therapy?
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pt with cavitary lesions, HIV +
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How should pt slow to respond to therapy be treated?
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9 months and at least 6 months from the time they convert smear and culture negative
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If smear is negative, wil culture be negative?
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not always
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How long is tx when isoniazid and rifampin can't be used?
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2 years or more
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What are 2 things that should be avoided in active TB tx?
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monotherapy
adding a single drug to a failing regimen |
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Why should adding one drug to a failing therapy be avoided?
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leads to sequential selection of drug resistance until no drugs are left
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When should drug resistant TB be suspected?
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- patients who have prior therapy for TB
- pts from areas of high resistance - homeless, institutionalized, IV drug abusers, HIV+ - +acid fast bacilli sputum after 1-2 months tx - + cultures after 2-3 months of therapy - pt who fails tx or relapse after tx - pt exposed to MDR-TB |
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What is XDR-TB?
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extensively drug resistan TB
resistant to at least isoniazid, rifampin, FQ, and a second line injectable drug (amikacin, capreomycin, kanamycin) |
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What drugs have better CNS penetration for CNS TB?
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isoniazid, pyrazinamide, ethionamide, and cycloserine
tx is longer for CNS |
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What FQ is preferred for CNS TB?
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levofloxacin
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How is extrapulmonary TB of soft tissue treated?
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conventional regimens
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When are corticosteroids stongly recommended for extrapulmonary TB?
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pericarditis
CNS TB, including meningitis |
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What is tx for TB in children?
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regimen similar to adult
prefer extended tx - 9 months pediatric rifampin and isoniazid dosing mg/kg is higher than adults |
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Does TB pose a risk to the baby in pregnant women?
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yes
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What is tx for pregnant women?
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isoniazid, rifampin, and ethambutol for 9 months
B vitamins should also be provided |
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What rare SE does rifampin have in pregnant women?
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birth defects, limb reduction and CNS lesions
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Why should streptomycin be avoided in pregnancy?
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can cause hearing loss or complete deafness to baby
other AG also only use in critical situations when alternatives do no exist |
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Why should ethionamide be avoided in pregnancy?
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may cause premature delivery and congenital deformities
may cause mongolism |
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Why is cycloserine not used in pregnancy?
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crosses placenta
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Why should FQ be avoided in pregnancy?
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may cause permanent damage to cartilage in weight bearing joints
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Are TB drugs excreted in milk?
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most are, but not enough to cause toxicity
FQ should be avoided |
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How should latent TB be tx in pregnant?
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wait until after pregnancy and treat with isoniazid
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Are intermittent regimens recommended for HIV?
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no
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How long should TB tx be in HIV?
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9 months
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Is isoniazid or rifampin renally dosed?
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typically no, excreted through liver
if peripheral neuropathies develop decrease frequency of dosing |
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What TB drugs are renally dosed?
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pyrazinamide and ethambutol
decrease dose from daily to three times weekly AG (amikacin, kanamycin, streptomycin), capreomycin, ethambutol, cycloserine, and levofloxacin extend dosing interval |
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What drug metabolites are cleared by kidneys?
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isoniazid, pyrazinamide, and p-aminosalicylic acid
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What drug metabolites are cleared hepatically?
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ethionamide
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What should be performed in renal failure pts taking cyclosering to avoid dose related toxicities?
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serum concentrations
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What drugs are mostly hepatic cleared?
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isoniazid, refampin, pyrazinamide, ethionamide, and p-aminosalicylic acid
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What drugs may cause hepatotoxicity?
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isoniazid, reifampin, pyrazinamide mainly
less: ethionamide, p-aminosalicylic acid rarely: ethambutol |
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What drugs can be used as "liver sparing" regimen?
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streptomycin, levofloxacin, and ethambutol
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What is a drawback of "live sparing" tx?
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18+ months of tx
usually switched to isoniazid and rifampin regimens as soon as able |
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How should drugs be dosed in morbidly obese pt?
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hydrophillic drugs dose with IBW initially, then adjust dose based on serum levels
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What are hydrophillic drugs?
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isoniazid, pyrazinamide, AG, capreomycin, ethambutol, p-aminosalicylic acid, and cycloserine
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What is isoniazid MIC against M. tuberculosis?
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0.01-0.25mcg/ml
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What routes can isoniazid be given?
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PO, IV (short), and IM
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Should isoniazid be taken with food or on an empty stomach?
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empty stomach
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What is metabolite of isoniazid?
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acetylisoniazid
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Why are some people slow acetylators of isoniazid?
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genetic, lack of N-acetyltransferase 2
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What population are mostly fast acetylators of isoniazid?
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asians and eskimos
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What population has a risk of hepatotoxicity when taking isoniazid fast or slow acetylators?
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slow
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What are risk factors for hepatotoxicity when taking isoniazid?
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patient age, preexisting liver disease, excessive alcohol intake, pregnancy, and postpartum state
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Who are at increased risk of neurotoxicity when taking isoniazid?
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pt with pyridoxine deficiency: pregnant women, alcoholics, children, malnourished
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What are symptoms of neurotoxicity in isoniazid?
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peripheral neuropathy
seizures and coma in overdose |
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What drugs does isoniazid inhibit metabolism of?
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phenytoin, carbamazepine, primidone, and warfarin
may need to adjust dose |
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What is the big advantage of the addition of rifampin to TB tx?
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shortens tx to 6-9 months compared to 18+
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What causes rifampin resistance?
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changes in rpoB gene
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What routes is rifampin given?
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oral and IV (short)
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Should oral rifampin be given with food or empty stomach?
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empty stomach
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What populations have difficulty absorbing rifampin?
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AIDS, diabetes, GI problems
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What is rifampins metabolite?
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25-desacetylrifampin
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Where is rifampin cleared?
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bile
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What are the most common adverse effects of rifampin?
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rash, fever, GI distress, increased hepatic enzymes
acute renal failure can also occur may turn urine and other secretions orange-red and may permanently stain some types of contact lenses |
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What drug interactions does rifampin have?
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induces CYP3A4, may enhance elimination of many drugs including:
protease inhibitors for HIV, oral contraceptives |
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What should HIV take instead of rifampin if on protease inhibitor?
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rifabutin
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What rifamycin can be used once weekly?
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rifapentine a long acting rifamycin
used in HIV negative pt only |
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What drug when given in the first 2 months with isoniazid and rifampin shortens duration to 6 months?
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pyrazinamide
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What are the most common toxicities for pyrazinamide?
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GI distress, arthralgia, and elevated serum uric acid (not true gout though)
hepatotoxicity is major limiting adverse effect and is dose related |
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What is Rifater?
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rifampin 120mg, isoniazid 50mg, and pyrazinamide 300mg
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What is Rifater typical daily dose?
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5-6 tablets daily
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What is Rifamate?
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isoniazid 150mg and rifampin 300mg
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What should ethambutol not be given with?
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antacids
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What is the renal dose for ethambutol?
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3x per week
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What is the major adverse effect of ethambutol?
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retrobulbar neuritis
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What other adverse effects does ethambutol have and how do you monitor?
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change in visual acuity - monitor using Snellen wall charts
inability to see the color green - monitor with Ishihara red-green color discrimination cards |
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What are the first line drugs for TB?
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isoniazid, rifampin, rifabutin, rifapentine, pyrazinamide, ethambutol
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What are the 2nd line drugs for TB?
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cycloserine, ethionamide, streptomycin, amikacin-kanamycin, capreomycin, p-Aminosalicylic acid(PAS), levofloxacin, moxifloxacin, gatifloxacin
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What AG are active against mycobacteria?
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streptomycin, amikacin, and kanamycin
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What route is streptomycin given?
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IV and IM
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Is streptomycin renally dosed?
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yes, give less often
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What adverse effects with streptomycin?
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nephrotoxicity and ototoxicity
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What is Paser?
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p-Aminosalicylic Acid
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What route is p-Aminosalicylic Acid given?
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po as an enteric-coated sustained release granule
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What adverse effect is associated with p-Aminosalicylic acid?
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diarrhea, self limiting, usually improves over 1-2 weeks
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How often is p-Aminosalicylic acid given?
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BID or TID
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What should pt know about p-Aminosalicylic acid?
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granules will appear in stool
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What adverse effect can occur when p-aminosalicylic acid and ethionamide are given together?
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goiter
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What drug is only given for MDR-TB?
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cycloserine
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What can be given to imporve pt tolerance of cycloserine?
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pyridoxine
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How is cycloserine cleared?
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kidneys, reduce dose in renal failure
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What adverse effects with cycloserine?
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CNS toxicity: lethargy, confusion, unusual behavior
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What should serum concentration of cycloserine be for therapy?
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20-35mcg/mL 2 hours postdose
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Should dose of cycloserine be changed if having mild CNS effects like difficulty concentrating?
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no
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When should serum concentration for cycloserine be checked?
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1-2 weeks into therapy
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Is ethionamide static or cidal?
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static, need to high concentration for cidal
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What is dose limiting toxicity for ethionamide?
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GI toxicity
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Should ethionamide be given with food?
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may be given with light snack or before bedtime to minimize GI intolerance
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Is ethionamide renally dosed?
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no
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What are AE of ethionamide?
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gynecomastia, alopecia, impotence, menorrhagia, photodermatitis, acne
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When is clofazimine used?
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advanced cases of MDR-TB or MAC
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What are most important SE of clofazimine?
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GI distress and skin discoloration
severe GI pain may occur from deposition of crystals in intestines |
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Why is thiacetazone used sometimes?
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cheap
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What is major SE of thiacetazone?
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skin reaction and SJS
d/c permanently if rash appears |
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What FQ are used to tx MDR-TB?
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levofloxacin, ciprofloxacin, and moxifloxacin
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Which FQ is being studied to replace 1st line agents?
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moxifloxacin
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What B-lactam has some activity against rapidly growing mycobacteria?
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Cefoxitin, a B-lactamase stable cephalosporin
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When is the only time B-lactam with B-lactamase is used for TB?
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no other options
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Are macrolides used for TB?
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not frequently
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What drug chemically related to metronidazole has activity against TB?
|
nitroimidazopyran PA 824
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What must be monitored when taking linezolid?
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hematologic indices for anemia and thrombocytopenia
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What delivery system is bein investigated for TB use?
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liposomes
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What is BCG vaccine?
|
bacille Calmette-Guerin Vaccine
atenuated hybridized strain of M. bovis prophylactic vaccine against TB |
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How does BCG work?
|
produces a subclinical infection resulting in sensitization of T lymphocytes and cross immunity to M. tuberculosis
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What effect does BCG have on skin test?
|
gives a positive skin test
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What is primary benefit of BCG vaccine?
|
prevention of severe forms of TB in children
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Who should avoid BCG vaccine?
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pregnant and IC
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When should HIV receive BCG vaccine?
|
HIV infants who are asymptomatic with high risk of TB should be given vaccine at birth
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When is BCG used in US?
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in uninfected children where TB is unavoidable, used very little
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What is the most serious problem with TB therapy?
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nonadherence
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How often should acid-fast bacilli stains be done if positive?
|
every 1-2 weeks until 2 consecutive smears are negative
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How often should sputum cultures be done if on maintenance therapy?
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monthly until 2 consecutive negative, generally 2-3 months
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When should hepatotoxicity be suspected when on TB tx?
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if transaminase >5x upper limit of normal, or total bilirubin >3mg/dl
n/v and jaundice |
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What drug should audiometric testing be performed?
|
streptomycin for >1-2 months
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What drug should vision testing be performed for?
|
ethambutol
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What should all pts diagnosed with TB be tested for?
|
HIV
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What pts should therapeutic drug monitoring be used in?
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if failing therapy, AIDS, diabetes, cystic fibrosis, GI disorders, hepatic or renal disease
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