Mycobactreria Flashcards
Leprosy is also called
Hansen disease
Leprosy (Hansen disease) is caused by
Mycobacterium leprae
Mycobacterium leprae - stracture
acid-fast bacillus
Mycobacterium leprae - reservoir in US
amradilos
Mycobacterium leprae - area of infection
it likes cool temperatures (infect skin and superficial nerves - glove and stocking loss of sensation
Mycobacterium leprae - in vitro
cannot grow
Leprosy (Hansen disease) - how many forms and which
- Lepromatous
2. Tuberciloid
Leprosy (Hansen disease) - lepromatous form - clinical manifestation
presents diffusely over the skin, with leonine (lion-like) facies, and is communicable
Leprosy (Hansen disease) - lepromatous form - immune system
low cell-mediated immunity with humoral Th2 response
Leprosy (Hansen disease) - Tuberciloid form - clinical manifestation
limited to few hypoesthetic. hairless skin plaques
Leprosy (Hansen disease) - Tuberciloid form - immune system
high cell-mediated immunity with a largely Th1 type response response
Leprosy (Hansen disease) - Treatment
dapsone with rifampin for tuberciloid dorm
clofazimin is added n lepromatous form
primary tuberculosis is caused by
infection with Mycobacterium tuberculosis of a Nonimmune host (usually host) (infection of previous unexposed individual)
secondary tuberculosis is caused by
- reinfection (infection with Mycobacterium tuberculosis of a partially immune hypersensitized host - usually adult)
- Reactivation due to immunosuppression
primary tuberculosis - lesion
Ghon complex: Hilar nodes + Ghon focus (calcified TB granuloma forming a nodule) usually in lower to middle lung
secondary tuberculosis after reactivation - lesion
fibrocaseous cavitary lesion (usually upper lobes)
Primary tuberulosis may lead to
- heals by fibrosis (immunity and hypersensitivity/PPD+)
- progressive lung disease (hiv/malnutrition)
- Miliary tuberulosis –> Death
- Preallergic lymphatic or hematogenous dissemination (dormant tubercle bacilli in several organs/reactivation in adult life)
Extrapulmonary tuberculosis - sites?
- CNS (parencymal tuberculoma or meningitis)
- Vertebral body (Pott disease)
- Lymphadenitis
- Renal
- GI
- Adrenals
Reactivation of tuberculosis in the lung lead to
- secodary tuberculosis fibrocaseous cavitary lesion (usually upper lobes)
- extrapulmonary tuberculosis
TB - primary tuberculosis occurs most commonly in
TB - secondary tuberculosis occurs most commonly in
1ry: children
2ry: adults
priamry tuberculosis - next step (and proportions)
- healing by fibrosis calcification (more than 90%)
2. Progressive 1ry tuberculosis esp on AIDS, malnutrition (less than 10%
Pott disease
tb in vertebral body
CNS TB?
parencymal tuberculoma or meningitis
TB - PDD positive if
- current infection or past exposure
2. false positive with BCG vaccination (further workup required)
TB - PDD negative if
- no infection
- anergic (steroids, malnutrition, immunocompromised)
- sarcoidosis
tests to diagnose TB
- PPD
2. Interferon-γ release assays (IGRA)
PPD vs Interferon-γ release assays (IGRA)
IGRA has fewer false positives from BCG vaccination
Mycobacteria - bugs?
- Mycobacterium tuberculosis
- Mycobacterium avium-intracellulare
- Mycobacterium scrofulaceum
- Mycobacterium marinum
- Mycobacterium leprae
Mycobacterium tuberculosis - clinical manifestation
TB - fever, night sweats, weight loss, cough (non-productive or productive), hemoptysis
TB - cough - non-productive or productive?
both
Mycobacterium avium-intracellulare - causes
disseminated non-TB disease in AIDS
Mycobacterium avium-intracellularee - prophylaxis
azithromycin when CD+ cound under 50
or rifabutin
Mycobacterium scrofulaceum causes
cervical lymphadenitis in children
Mycobacterium marinum causes
hand infection in aquarium handlers
Cord factor is found in
the cell wall of Mycobacterium (in virulent stains) –> creates a “serpentine cord” appearance in virulent M. tuberculosis
Cord factor - function
inhibits macrphage maturation and induces releases of TNF-α
Mycobacterium - Sulfatides?
surface glycolipids inhibit phagolysosomal fusion
Mycobacteria - bugs and diseases
- Mycobacterium tuberculosis –> TB
- Mycobacterium avium-intracellulare –> disseminated non-TB disease in AIDS
- Mycobacterium scrofulaceum –> cervical lymphadenitis in children
- Mycobacterium marinum –> hand infection in aquarium handlers
- Mycobacterium leprae –> Leprosy (Hansen disease)
Ziehl-Neelsen (carbol fuschin) stains
Acid-Fast bacteria (Nocardia, Mycobaceria) and protozoa (Cryptosporidium oocysts)
mycobacteria - special characteristic of the structure (and clinical relevance)
cell wall are high in mycolic acid - detected by carbolfuchin in acid-fast stain
Special culture requirements - Mycobabterium Tuberculosis - media?
Lowenstein-Jensen agar
M. tuberculosis - prophylaxis and treatment
prophylaxis: isoniziad
treatment: 1. rifampin 2. Isoniazid 3. Pyrazinamide 4. Ethambutol (RIPE)
M. intracellulare-avium - prophylaxis and treatment
prophylaxis: azithromycin, rifabutin
treatment: Azithromycin or clarithromycin + ethambutol
Can add rifabutin or ciprofroloxacin
M leprae - prophylaxis and treatment
prophylaxis: N/A
treatment: Long-term treatment with dapsone and rifampin for tubrrculoid form. Add clofazimine for Lepromatous form
Antimycobacterial drugs - groups and drugs
- Mycolic acid synthesis –> isoniazid
- Arabinoglycan synthesis (Arabinosyl tranferase) –> ethambutol
- mRNA synthesis (DNA-dependent RNA polymerase) –> Rifamycins (rifabutin, rifampin)
- Intracellular (unclear mechanism) –> pyrazinamide
- streptomycin
mycobacterial cell is composed by - from outer to inner
outer - acyl lipids, complex free lipids - mycolic acid - arabynogalactan - peptidoglycan - inner
Rifamycins - drugs and mechanism of action
Rifampin, rifabutin
inhibit DNA-dependent RNA polymerase
Rifamycins - drugs and clinical use
Rifampin, rifabutin
- Mycobacterium tuberculosis treatment
- Leprosy: delay resistance to dapsone
- Meningicoccal prophylaxis
- Chemoprophylaxis in contacts of children with H. influenzae type B
- Can add in M. Avium-intracellulare (rifabutin)
- M. Avium-intracellulare prophylaxis
Rifamycins - action on leprosy
delay resistance to dapsone
Rifamycins - toxicity
- Minor hepatotoxicity
- Drug interactions (increases cytochrome P-450) - esp rifampin
- orange body fluids (nonhazardous side effect)
Rifamycins - drugs interaction by
increases cytochrome P-450 - esp rifampin
Rifamycins - HIV
RIfabutin favored over rifampin in HIV patients due to LESS cytochrome P-450 stimulation
Rifampin vs rifabutin according to side effects
Rifampin increases P450 much more than Rifabutin
Rifamycins - resistance
mutation reduce drug binding to RNA polymerase
–> monotherapy leads to resistance
Isonizid (INH) - mechanism of action / aka
Bacterial catalase peroxidase (encoded by KatG) needed to convert Isonizid (INH) to active metabolite –> decreases synthesis of mycolic acid. aka: INH
what is needed to convert Isonizid (INH) to active metabolite
Bacterial catalase peroxidase (encoded by KatG)
Isonizid (INH) - clinical use
- Mycobaterium tuberculosis prophylaxis
2. Mycobaterium tuberculosis treatment
Isonizid (INH) - resistance
Mutation leading to underexpression of KatG (bacterial catalase peroxidase)
bacterial catalase peroxidose is encoded by
KatG
Isonizid (INH) - toxicity
- hepatotoxicity
- P-450 inhibition
- drug induced SLE
- vitamin 6 - pyridoxine (B6) deficiency (–> peripheral neuropathy, siderblastic anemia)
Isonizid (INH) - solution of toxicity
vitamine 6 (Pyridoxine) can prevent neurotoxicity and anemia
Isoniazid - half-lives
different Isonizid (INH) half-lives in fast vs slow acetyators
Pyrazinamide - mechanism
mechanism uncertain
Pyrazinamide is a prodrug that is converted to tha active compound pyrazinoic acid
WORKS BEST at acidic ph (eg. in host phagolysosomes)
Pyrazinamide - active compound
pyrazinoic acid
Pyrazinamide - clinical use
treatment of Mycobacterium Tuberculosis
Pyrazinamide - toxicity
- hyperuricemia
2. hepatotoxicity
Ethambutol - mechanism of action
decreases carbohydrate polymerization of mycobacterium cell wall by blocking arabinosyltranferase
Ethambutol - clinical use
- treatment of Mycobacterium Tuberculosis
2. treatment of Mycobacterium acium-intracellulare
Ethambutol - toxicity
Optic neuropathy (red green color blindness)
M. tuberculosis and M.avium-intracellulare - prophylaxis and prevention
M. TUBERCULOSIS:
prophylaxis: isonizid
treatment: 1. rifampin 2. Isoniazid 3. Pyrazinamide 4. Ethambutol (RIPE)
M. avium-intracellulae
prophylaxis: azithromycin, rifabutin
treatment: Azithromycin or clarithromycin + ethambutol
Can add rifabutin or ciprofroloxacin
M leprae - prophylaxis and treatment
prophylaxis: N/A
treatment: Long-term treatment with dapsone and rifampin for tubrrculoid form. Add clofazimine for Lepromatous form
TB - PDD positive if
- current infection or past exposure
2. false positive with BCG vaccination (further workup required)
TB - PDD negative if
- no infection
- anergic (steroids, malnutrition, immunocompromised)
- sarcoidosis
Streptomycin - mechanism of action
inerferes with 30S compoment of ribosome
Streptomycin - clinical use
M. tuberculosis
Streptomycin - adverse effects
- Tinnitus
- Vertigo
- ataxia
- nephrotoxicity