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2. HDS Pulmonary > Mycobacteria, Other AFB, Antimycotic Agents > Flashcards

Mycobacteria, Other AFB, Antimycotic Agents Flashcards

1
Q

Mycobacteria

Morphology and Cultivation

A
  • Slender, straight or slightly curved rods (1-4 cm)
  • Colonies appear rough, granular, and buff-colored
  • Some atypical mycobacteria are rapid growers
  • Most very slow growing, including M. tuberculosis
    • Generation time up to 18 hrs
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2
Q

Mycobacteria

Species

A
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3
Q

Mycobacterial Infection

Classification

A
  • Mycobacerium tuberculosis
    • ~ ⅓ of world population infected
    • Humans only known reservoir
    • 85% of TB cases present with pulmonary sx
  • Mycobacterium avium-intracellular
    • Atypical mycobacteria
    • Ubiquitously found in fresh and salt water worldwide
    • Usu. only infects immunocompromised pts
    • Mostly pulmonary disease but also infects other tissues
  • Mycobacterium leprae
    • Causes leprosy
    • Infects skin and peripheral nervous system
    • Very slow growing ⇒ progressive course over a long time
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4
Q

Mycobacteria

Properties

A
  • Aerobic
  • Bacillus ⇒ slender straight or curved rods
  • Highly resistant to:
    • Drying
    • Many disinfectants
    • Acids
    • Alkalis
  • Heat sensitive
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5
Q

Mycobacteria

Cell Wall

A

Lipids are 60% of cell wall structure

Inside ⇒ outside:

  1. Cytoplasmic membrane
  2. Lipoarabinomannan (LAM)
    • Anchored to cell membrane
    • Functionally related to O-antigen of LPS
  3. Murein ⇒ thick peptidoglycan layer
    • 2 chains of alternating sugars linked by polypeptide chains
  4. Arabinogalactan ⇒ polymer consisting of arbinose and galactose
    • Attached to cell wall & mycolic acid chains
  5. Mycolic acids ⇒ long alkyl chains
    • Each arabinogalactan attached to 60-90 myolic acid chains
    • Forms waxy protective lipid shell
    • Additional lipids also present
    • Reason for resistance to acid decolorization
      • Do not take up dyes in gram staining
    • Contributes to abx resistance
  6. Outer membrane of secreted phospholipids
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6
Q

Mycobacteria

Visualization

A
  • Ziehl-Neelson or Kinyoun stains ⇒ bacteria that retain the primary stain after decolorization are called acid-fast ⇒⇒ Mycobacteria called acid fast bacilli (AFB)
    1. Apply primary stain, carbol fuchsin
    2. Decolorize with acid alcohol
    3. Counterstain with methylene blue
  • Visualize by fluorescent staining ⇒ Auramine-rhodamine
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7
Q

Tuberculosis

Epidemiology

A
  • Globally:
    • ~ 2.3 billlion Latent TB Infections (LTBI)
    • ~ 9 million new active cases / yr
    • ~ 1.4 million deaths / yr
    • 22 countries have 80% of all TB cases
  • USA:
    • ↑ incidence since 1985
      • Likely d/t AIDS epidemic
    • ↓ since 1993
      • TB control programs
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8
Q

Tuberculosis

Transmission

A
  • Via inhalation of mycobacteria in droplet nuclei
    • ~ 3,000 in a single cough
  • < 10 bacilli may initiate infection
  • Droplet nuclei dry and may become airborne
    • Remains infectious for extended periods
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9
Q

Tuberculosis

Transmission Risk Factors

A
  • Overcrowded areas
  • Prisons
  • Foreign born
  • HIV-infection
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10
Q

Tuberculosis

Invasion

A

Facultative intracellular pathogens

  • Ingested by alveolar macrophages
  • Grow within non-activated MΦ and outside of them
  • Prefers sub-pleural location near fissures
  • Lesion development, progression, and resolution depends on:
    • # of mycobacteria inhaled
    • Subsequent multiplication
    • Host immune response
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11
Q

M. tuberculosis

Virulence Factors

A
  • Facultative intracellular pathogen
    • Able to grow within MΦ
  • Liproarabinomannan (LAM)
    • ⊗ MΦ activation
    • Scavenges oxygen radicals
    • ⊗ Phagolysosome fusion
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12
Q

TB

Exposure

A
  • ⊕ Contact with a person w/ contagious pulmonary TB
  • ⊖ PPD skin test
  • Normal CXR
  • Some exposed persons develop infection w/ subsequent PPD conversion, others do not
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13
Q

Tuberculosis

Infection

A
  • ⊕ PPD skin test
  • No physical findings of disease
  • CXR normal or reveals old granulomas or calcifications in lung or regional lymph nodes
  • Requires preventative therapy
  • 90% remain asymptomatic
  • ~ 5% develop disease within 2 years of infection ⇒ primary TB
  • ~ 5% develop disease at some later time ⇒ reactivation disease
    • Usually d/t ↓ immune response with age, immunosuppressive disease, or therapy
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14
Q

Tuberculosis

Disease

A

Infected individual with signs, symptoms, and/or radiographic findings consistent with disease.

May be pulmonary and/or extrapulmonary.

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15
Q

Tuberculosis

Clinical Infection

A

Characterized as a chronic pneumonia.

Onset is insidious.

Primary TB is usually mild.

  • TB is an indolent, wasting, fibrile illness
    • Chronic productive cough ± hemoptysis
    • Fatigue
    • Weight loss
    • Night sweats
    • Weakness
    • Fever
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16
Q

TB

Primary Infection

A

Varies: completely asymptomatic → primary progressive disease

  • Early during infection prior to immune response ⇒ organisms grow uninhibited @ pulmonary & additional sites
  • Tubercle or Ghon focus ⇒ productive granuloma caused by mycobacteria
    • Center ⇒ multinucleated giant cells containing organism ± caseous necrosis
    • Middle ⇒ epitheloid cells
    • Outer ⇒ fibroblasts, lymphocytes, and monocytes
  • Ghon complex ⇒ granuloma within the lung and within a draining hilar LN
  • Granuloma may heal by fibrosis and calcification ⇒ lung scarring
  • May result in lymphohematogenous spread throughout body & seeding of lung apices
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17
Q

Progressive Primary TB

A
  • May directly result from lesion eroding into bronchioles ⇒ cavitation & dissemination within lung
  • Lymphohematogenous spread ⇒ remote dissemination ⇒ miliary tuberculosis
  • Child < 5 y/o @ high risk for progressive 1° TB
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18
Q

Secondary Pulmonary TB

Etiology

A
  • Most cases d/t reactivation of latent TB
    • Usually in apical portion of lung
    • Leads to chronic pulmonary diseases w/ 1 or more productive lesions
    • Associated with conditions that ⊗ immune system
      • Alcoholism
      • DM
      • Old age
      • Immunosuppressive therapy
      • AIDS
  • Can result from an exogenous secondary infection
    • Exposed to TB again
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19
Q

Secondary Pulmonary TB

Manifestations

A
  • Cough
  • Fever
  • Fatigue
  • CXR ⇒ usually show upper lobe involvement with a cavitary lesion
  • ± TB pleurisy w/ rupture of cavity or granuloma into pleural space ⇒ empyema
  • Sputum smear and PPD usually ⊕
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20
Q

Miliary Tuberculosis

A

Dissemination and seeding of TB bacilli to various distant organs.

  • Develop infectious foci in meninges, urogenital tract, peritoneum, skin, bones, etc
  • Usually occurs in immunocompromised individuals
  • Most commonly occurs w/ primary infection
    • Can also occur during reactivation
  • Focal sx may be absent ⇒ difficult to dx
  • PPD skin test often ⊖
  • Communicability of miliary TB relatively low
  • If lungs involved, CXR shows “miliary” pattern
  • Clinical manifestations:
    • Fever
    • Night sweats
    • Weight loss
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21
Q

Extrapulmonary TB

Meningitis

A
  • Indolent onset HA with systemic sx
  • CSF ⇒ PMNs early then lymphocyte predominance, low glucose, high protein
  • Imaging ⇒ enhancement of basilar meninges
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22
Q

Extrapulmonary TB

Renal Disease

A
  • Infection of renal parenchyma
  • Sx ⇒ dysuria, frequency, flank pain
    • Fever and systemic sx uncommon
  • Sterile pyuria ⇒ WBC in urine with no organisms
  • Organism frequently grows from urine if repeated AFB urine cultures performed
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23
Q

Extrapulmonary TB

Bone Disease

A
  • Spine affected in 50% of cases w/ bone involvement ⇒ Potts disease
  • Hips and knees less affected
  • Pts usually c/o pain
  • ± Fever
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24
Q

Extrapumonary TB

Local LN Disease

A
  • Most commonly occurs in children < 15 y/o
  • Can be caused by M. tuberculosis or M. scrofulaceum
  • Cervical lymph nodes most commonly involved ⇒ Scrofula
  • Dx ⇒ excisional biopsy or fine-needle biopsy
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25
Q

Extrapumonary TB

Other Sites

A
  • GI tract
  • Pericarditis
  • Peritonitis
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26
Q

TB & HIV

A
  • ↑ Prevalence of TB in HIV infection
  • All pts w/ TB need HIV testing and vice versa
  • Early HIV infection ⇒ presentation similar to immunocompetent host
    • Indolent onset of cough, fever, sweats
    • Extrapulmonary manifestations in 10-15%
    • CXR shows upper lobe infiltrates ± cavitation
    • PPD usually ⊕
  • Advanced HIV infection ⇒ atypical presentation
    • PPD usually ⊖
      • No immune response
    • CXR shows lower lobe or diffuse infiltrates
      • Cavitation rare
    • Extrapulmonary disease in > 50%
      • Often occurs w/o pulmonary disease
  • M. avium-intracellulare complex ⇒ causative agent of disseminated infection in AIDS pts
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27
Q

Mycobacteria

Immunity

A
  • Grow uninhibited within non-activated MΦ early during infection
  • Ingestion by MΦ ⇒ innate immunity activation
    • Release IL-12, TNF-α, IL-6, IL-1
  • PMNs, MΦ, and T-cells recruited to site
    • Lymphocytes activated in nearby lymph nodes
      • Can take 6-8 weeks
  • T-cell mediated response ⇒ containment and/or resolution
    • Releases IFN-𝛾 ⇒ activate MΦ
  • Activated MΦ can partially inhibit mycobacterial growth
  • Activated MΦ ⇒ epithelioid cells ⇒ granuloma ⇒ walls off infected cells ⇒ fibrosis and calcification ⇒ tubercle formation
    • Type IV hypersensitivity
  • Immune response limits infection but damages lung
    • Elimination vs immune injury varies w/ # of organisms present & strength of immune response
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28
Q

Tuberculosis

Clinical Diagnosis

A
  • Hx of compatible sx in pt w/ potential exposure or risk factors ⇒ high suspicion
  • Physical exam often nonspecific
  • Routine labs often nonspecific
    • May see normocytic anemia
    • May have elevated ESR
    • WBC count varies/may be normal
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29
Q

Tuberculosis

CXR

A

1° TB ⇒ lower lobe infiltrate ± Ghon complex

2° TB ⇒ upper lobe involvement ± cavity

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30
Q

Tuberculosis

Dx Staining

A
  • ⊕ Acid-fast smears only presumptive e/o TB
  • False ⊕ can occur from environmental contamination
  • ~60% of positive cultures ⇒ ⊕ smears
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31
Q

Tuberculosis

Dx Culture

A

Definitive dx by culture isolation only

  • Inoculated on complex media w/ organic substances
    • Egg yolk, animal serum, tissue extracts
    • Often contain abx or malachite green to inhibit growth of other macteria
  • Lowenstein-Jensen (solid medium) ⇒ slow growth 3-8 wks
  • Middlebrook 7H10 (liquid broth) ⇒ 1-3 weeks
    • Cannot grow all strains
    • Both cultures must be done
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32
Q

Mycobacteria

Biochemical Tests

A

Production of niacin

Distinguishes M. tuberculosis from atypical mycobacteria.

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33
Q

Nucleic Acid

Amplification Techniques

A

Rapid tests that ID M. tuberculosis in clinical specimens within a few hours.

  • Sensitivity for smear ⊕ specimens very high
  • Sensitivity for smear ⊖ specimens ~ 45-75%
  • Must still perform culture for sensitivity testing
  • Technically complex and very expensive
34
Q

IFN-𝛾 Release Assay

(IGRA)

A

Measure in-vitro IFN-𝛾 response to specific Mtb antigens.

  • Ag not present in non-tuberculous mycobaceria or BCG strains
  • Useful to screen individuals vaccinated with BCG
  • Blood test ⇒ only 1 visit
  • Technical complexity limits use
35
Q

Tuberculin Skin Test

(TST)

A
  • Useful for dx and control of TB
  • ⊕ Result ⇒ recent or past TB exposure
    • Have T-cells against AFB ⇒ Type IV DTH
    • No info on activity of disease
  • Mantoux test ⇒ most accurate and reliable
    • Intracutaenous injection of 0.1 ml of purified protein derivative (PPD)
  • ⊕ Rxn indicated by erythematous indurated area > 5-10 mm
    • See ⊖ results with infection in AIDS or other T-cell deficiencies ⇒ anergic
  • Requires pt to return for reading in 48-72 hrs
  • Two-step TST testing
    • See initial false ⊖ result d/t waning cutaneous immunity in remote infections
    • Can convert to ⊕ if 2nd TST w/in 2-3 weeks of initial test
    • Recommended for healthcare workers and elderly pts
36
Q

Urine Cultures

A

30-40% of urine cultures may be ⊕ in case of extrapulmonary infections

37
Q

Active TB

Treatment Overview

A
  • High mutation frequency leads to drug resistance ⇒ treat w/ multiple drugs simultaneously
  • Before abx sensitivity results available, treat according to risk for MDR infection
  • Initially all pts treated with 4 drugs
  • Susceptibility results w/o MDR disease ⇒ change to 3 drugs
  • Susceptibility results with MDR disease ⇒ change to 5 drugs based on resistance
  • Should have ⊖ sputum cultures in 85% after 2 months & 90-95% after 3 months
  • If sputum culture remains ⊕ after 3 months ⇒ consider non-adherence vs re-eval for resistance
38
Q

TB

Prevention

A
  • Purpose:
    • Prevent latent infection from progressing to clinical disease
    • Prevent initial infection
    • Prevent recurrence of past disease
  • Usual preventative therapy ⇒ isoniazid for 6 months in non-HIV pts
    • May be composed of up to 3 drugs
39
Q

TB

Vaccination

A
  • Give Bacillus Calmette-Guerin (BCG)
    • Attenuated strain of M. bovis
    • Used in several European and South American countries
  • 10-70% success rate in preventing TB infection
  • Effective in ↓ risk of miliary and meningeal forms of TB
  • Results in ⊕ PPD test
  • IGRA preferred screening test
40
Q

TB

Infection Control

A
  • Respiratory isolation when TB suspected
    • ⊖ Pressure room with doors closed
    • Providers use N95 masks
  • Respiratory isolation during first 2 weeks of treatment for confirmed TB
  • Contact tracing and screening programs
41
Q

Mycobacerium Avium Complex

(MAC)

A

M. avium-intracellulare

Common opportunist in immunocompromised pts esp. AIDS and transplant recipients.

  • Ubiquitous organism found in soil, fresh and salt water
  • Not transmitted person to person
  • Difficult to treat
    • More resistant to abx
    • Poor host immune status
42
Q

Norcardia

Overview

A
  • 3 species cause human disease
    • N. asteroides ⇒ most common
    • N. brasiliensis
    • N. cavae
  • Found in soil
  • Transmission
    • Inhalation ⇒ pulmonary infection
    • Direct inoculation into skin or subQ tissue
  • Infection may disseminate hematogenously ⇒ many organ systems
    • Predilection for brain abscess formation
43
Q

Norcardia

Morphology

A
  • Gram ⊕
  • Partially acid-fast
    • Have shorter myolic acid chains than Mycobacteria
  • Filamentous ⇒ looks like hyphal elements in tissue
    • Fragments ⇒ bacillary or coccoid forms
44
Q

Norcardia

Pathogenesis

A
  • Morbidity attack rate ~ 500-1K cases/yr
  • Non-communicable
  • Inhalation of organisms ⇒ lobar pneumonia
  • Metastatic foci may involve the brain, kidney, or skin
  • ⊗ Lysosome-phagosome fusion
45
Q

Norcadia

Pathological Features

A
  • Multiple abscesses w/ infiltration of PMNs and central necrosis
  • Burrowing sinuses and granulomas are not characteristic
46
Q

Norcardia

Diagnosis

A
  • Microscopic exam of sputum, skin lesions, and surgical materials
    • Look for gram ⊕ branched filaments
    • May mis-diagnose as TB
  • Grows on normal media over wide temp. range
    • Incubate @ 40-50°C ⇒ inhibit most other bacteria
  • Culture under aerobic conditions
47
Q

Norcardia

Treatment

A

Sulfonamides preferred

48
Q

Isoniazid

Indications

A

Part of drug combo for active and latent TB

Bactericidal against growing bacterial

Bacteriostatic against dormant bacteria

49
Q

Isoniazid

MOA

A
  • Prodrug activated via oxidation rxn by mycobacteria enzyme katG (catalase-peroxidase activity)
  • Active compound:
    1. Acylates inhA enzyme
      • Responsible for mycolic acid synthesis
    2. Acylates NADH dehydrogenase
      • Needed to catalyze the rxn
50
Q

Isoniazide

Resistance

A

Due to mutation in KatG, inhA, or NADH dehydrogenase

51
Q

Isoniazid

Metabolism

A

Extensively metabolized to inactive compounds:

  • N-acetyltransferase converts to N-acetylisoniazide
    • Isozymes ⇒ rapid vs slow acetylators
    • May have to adjust dose for rapid type
  • N-acetylisoniazide ⇒ N-acetylhydrazine
    • Substrate for CYP-450 ⇒ reactive intermediates
      • Damages liver proteins ⇒ hepatotoxicity
        • Slow acetylators more prone d/t build-up of metabolites
52
Q

Isoniazid

Adverse Effects

A
  • Elevation of serum transaminase
  • Age-dependent hepatitis
  • Peripheral neuritis
    • Due to Vit B6 (pyridoxine) depletion
    • Prevent w/ supplemental Vit B6
  • Drug-induced lupus in slow-acetylators
53
Q

Isoniazid

Drug Interactions

A
  • Phenytoin toxicity in slow-acetylators
  • Extra isoniazide inhibits hepatic microsomal enzymes
54
Q

Ethambutol

Indications

A

Used in combo to treat active TB & M. avium-intracellular

Bacterostatic @ low doses

Bactericidal @ high doses

55
Q

Ethambutol

MOA

A

⊗ arabinosyl transferase ⇒ ↓ arabinogalactan synthesis

Enzyme adds arabinose units to arabinogalactan chain

56
Q

Ethambutol

Resistance

A

Via over-expression of arabinosyl transferase.

57
Q

Ethambutol

Metabolism

A

Majority excreted into urine unchanged

58
Q

Ethambutol

Adverse Effects

A
  • Optic neuritis ⇒ blindness and/or vision impairment
    • Monitor visual acuity and color perception
  • Impairs red-green color discrimination
    • Eye exam required
59
Q

Pyrazinamide

Indications

A
  • Shortens duration of treatment when used in combo
  • Some e/o activity against non-replicating persistent mycobacteria
  • Bactericidal against even slow growing TB
60
Q

Pyrazinamide

MOA

A
  • Pyrazinamide ⇒ pyrazinoic acid by deamination by pyrazinaminidase
  • Transported to extracellular compartment via efflux pump
  • Protonated in acidic environment of phagolysosome
  • Protonated lipid soluble compound re-enters mycobacterium
  • ⊗ fatty acid synthase type I ⇒ ⊗ mycolic acid synthesis
  • May also work by acidifying intracellular environment
61
Q

Pyrazinamide

Resistance

A

Via mutations of pyrazinaminidase

62
Q

Pyrizinamide

Metabolism

A

Mostly hepatic metabolism

63
Q

Pyrazinamide

Adverse Effects

A
  • Hepatotoxicity
    • Related to dose and length of treatment
    • Usu. when given for > 2 months
  • Hyperuricemia
    • Due to inhibition of excretion
    • Monitor uric acid
64
Q

Rifampin

Indications

A

Bactericidal

  • Used in combo to treat:
    • Active TB
    • Mycobacterium leprae (Leprosy)
    • Legionella pneumophilia (Legionnaire’s disease)
  • Used for prophylaxis:
    • When isoniazid resistant
    • Where risk of hepatotoxicity is significant
    • Exposure to Neisseria meningitidis
    • Exposure to Haemophilus influenza type b
65
Q

Rifampin

MOA

A
  • Binds β subunit of DNA-dependent RNA polymerase (rpoB)
  • Forms stable drug-enzyme complex
  • ↓ chain formation in RNA synthesis
  • Good penetration into tissues and TB lesions
66
Q

Rifampin

Resistance

A

Due to alteration of DNA-dependent RNA polymerase (rpoB)

Resistance develops rapidly if used as a monotherapy.

67
Q

Rifampin

Metabolism

A

Mostly hepatic metabolism

Undergoes enterohepatic cycling

  • Causes significant CYP-450 induction
  • Repeated admins will ↓ drug concentration
68
Q

Rifampin

Adverse Effects

A
  • Can impair liver function ⇒ hepatitis
    • Alcohol ↑ risk
  • Red-orange discoloration of urine, tears, and saliva
  • Hypersensitivity reaction common
    • See flu-like illness w/ fever, chills, fatigue, and HA
  • Multiple drug interactions
    • Due to CYP-450 induction
    • Can ↓ effectiveness of anticonvulsants, oral contraceptives, and other drugs
69
Q

Rifabutin

A
  • Similar indications and MOA as rifampin
  • Less potent inducer to CYP-450
  • Used instead of rifampin to treat TB in HIV pts
  • Used for prevention and treatment of M. avium complex
70
Q

MDR-TB

Medications

A

Streptomycin and Amikacin

(aminoglycosides)

• Given parenterally, not as convenient

71
Q

TB Treatment

Challenges

A
  • Replicate more slowly
  • Can exist in a dormant state
  • Intracellular organisms
72
Q

TB Therapy

Principles

A
  • Drug combos always given to minimize development of resistance
    • Also shortens duration of therapy
  • Meds must be taken regularly
  • Therapy must continue for a period sufficient to resolve the illness
73
Q

Active Tuberculosis

Treatment

A
  • Confirm dx by culture and test for susceptibility
  • Standard initial phase treatment ⇒ daily doses of “RIPE”
    1. Rifampin
    2. Isoniazid
    3. Pyrazinamide
    4. Ethambutol or streptomycin
  • Once susceptibility shown ⇒ ethambutol/streptomycin can be discontinued
  • After 2 months ⇒ pyrazinamide stopped
    • Isoniazid and rifampin continued for 4 more months
      • 2-3 times per week
  • Rifabutin used in HIV pts for entire 6 month period
  • Normal course of treatment lasts 6 months
    • Pts with other comorbidities will require prolonged treatment
  • Sputum monitored weekly until no e/o TB
74
Q

Latent Tuberculosis

Treatment

A

~10% develop active TB over lifetime s/p infection

Must exclude active disease before treatment for latent TB

  • Candidates for prophylaxis
    • Known exposure to someone with active TB until ⊖ TST
    • Pts who recently converted to ⊕ TST
    • ⊕ TST w/ risk for progression from latent to active TB
  • Possible drug regimens
    • Isoniazid (INH) 300 mg/d x 6-9 months
    • Rifampin (RIF) daily for 3-4 months
    • Weekly isoniazid + rifapentine for 3 months
      • Only with directly observed treatment (DOT)
75
Q

Drug-resistant TB

A
  • Improper drug use ⇒ resistance
  • 17% of newly dx TB cases resistant to 1 or more first-line agents
    • Isoniazide most common (10%)
  • Treat longer with drugs that are active
  • Multidrug-resistant TB (MDR-TB) ⇒ caused by organism that is resistant to at least isoniazid and rifampin
  • Extensively drug resistant TB (XDR-TB) ⇒ caused by organism resistant to isnoiazid, rifampin, and other drugs
    • Fluoroquinolones and one of Amikacin, Kanamycin, Capreomycin
76
Q

Mycobacterium avium-intracellulare

Treatment

A
  • Must determine if disease actually present or part of environmental contamination
  • Triple therapy for newly dx patients ⇒ administered 3x/week and 12 months after last negative culture
    (Put your MAC to REM sleep)
    1. Rifampin
    2. Ethambutol
    3. Macrolide ⇒ charithromycin or azithromycin
  • Azithromycin used for prophylaxis in immunocompromised pts
77
Q

Mycobacterium leprae

Treatment

A
  • ↓ Prevalence worldwide since WHO provided free multidrug therapy
  • Therapy depends on severity of disease
    • Tuberculoid leprosy (paucibacillary)
      • Bacterial burden low
      • Only 2 drugs recommended
        1. Dapsone
        2. Rifampin
    • Lepromatous leprosy
      • Most severe form
      • Requires 3 drugs
        1. Dapsone
        2. Rifampin
        3. Clofazimine (orphan drug)
      • Treatment is for 2-5 years
78
Q

Dapsone

Indications

A

Used primarily to treat leprosy.

May be used for other indications.

79
Q

Dapsone

MOA

A
  • Competitive ⊗ of dihydropteroate synthase
  • Analogue of para-aminobenzoic acid
  • Similar to sulphonamides ⇒ wide spectrum of activities
    • Antibacterial
    • Antiprotozoal
    • Antifungal
80
Q

Dapsone

Metabolism

A
  • Retained up to 3 weeks in skin, muscle, and esp. liver & kidney
  • Primarily metabolized in the liver
  • 70-85% slowly excreted in urine
  • Enterohepatic recirculation of free drug prolongs half-life
81
Q

Dapsone

Adverse Effects

A
  • Severe hemolysis in pts with G6PD deficiency
  • Skin rashes
  • Reversible peripheral neuropathy
  • Blurred vision
82
Q

Mycobacteria Drugs

Summary

2. HDS Pulmonary (28 decks)

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