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Microbiology Lecture Slides > Antimycobacterial Therapies I > Flashcards

Antimycobacterial Therapies I Flashcards

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1
Q

Reduces the bacillary population rapidly thereby decreasing severity of the disease, preventing death and halting transmission

A

Antituberculosis therapy

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2
Q

Eradicates persisting bacilli in order to achieve durable cure (prevent relapse) after completion of therapy

A

Antituberculosis therapy

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3
Q

Source of streptomycin & other antibiotics

A

Streptomyces griseus

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4
Q

Indicated for multi-resistant TB, which is resistant to both isoniazid and rifampin

A

Second-line anti-TBs

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5
Q

Multi-resistant TB (MDR-TB) is resistant to both

A

Isoniazid and Rifampin

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6
Q

Extensively drug-resistant TB (XDR-TB) is an MDR + resistance to a

A

Fluoroquinolone and an injectable aminoglycoside

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7
Q

Less effective and have significant toxic-side effects

A

Second-line anti-TBs

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8
Q

Kills Mtb by targeting arabinogalactan synthesis

A

Ethambutol

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9
Q

INH, ETA and PAS inhibit

A

Mycolic acid synthesis

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10
Q

Inhibits DNA synthesis and supercoiling by targeting topoisomerase

A

Fluoroquinolone

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11
Q

Inhibits RNA synthesis by targeting RNA polymerase

A

Rifampin

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12
Q

Inhibits protein synthesis by targeting the 30S ribosomal subunit

A

Streptomycin

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13
Q

Targets 23S ribosomal RNA, inhibiting peptidyl transferase

A

Macrolides

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14
Q

Inhibits protein synthesis in dormant bacteria Most likely has other targets

A

Pyrazinamide

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15
Q

Isoniazid, ethaionamide, and p-aminosalicylic acid inhibit

A

Mycolic acid synthesis

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16
Q

Inhibits cell wall synthesis (arabinogalactan synthesis)

A

Ethambutol

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17
Q

TMC-207 (bedaquiline) inhibits

A

ATP synthase

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18
Q

TB bacteria live (hide) within macrophages. As immunity decreases through aging and/or immune suppression, the dormant bacteria reactivate, causing

A

Outbreak of disease

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19
Q

4-9 months of treatment is needed for

A

TB

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20
Q

How long does it take to identify resistant strains of TB?

A

3-8

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21
Q

Natural resistance is always due to

A

Chromosomal mutation

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22
Q

For a smear-negative and culture-negative pulmonary tuberculosis in adults. The initial phase is

A

2 months of INH, RIF, EMB, and PZA daily

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23
Q

They are related to Gram-positives, but many members of the group have envelopes extremely rich in lipid and cannot be Gram-stained

A

Mycobacteria

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24
Q

Myobacteria cells, once stained, retain dye even under stringent decolorization with acid alcohol. Because of this they are designated

A

Acid-fast becateria (AFB)

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25
Q

Envelopes of Mycobacterium and related genera contain long-chain

A

Mycolic acids

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26
Q

A non-pathogenic genus of mycobacteria, and is the source of many antibiotics

A

Streptomyces

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27
Q

Fungi are the commercial source of

A

B-lactams

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28
Q

Gram-positive rods in which the long sides of the rods are not parallel, so cells are spindle- or club-shaped

A

Corynebacterium

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29
Q

On smears cells often form ‘V’ or ‘W’ forms.

-The group is large and taxonomically complex and its classification changes rapidly

A

Corynebacterium

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30
Q

Humans are its only host; transmission is by the respiratory route

A

Corynebacterium diphtheriae

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31
Q

Causes Diphtheria, a severe inflammation of the URT with formation of a thick grey ‘pseudomembrane’ composed of fibrin, leukocytes, and dead cells, on the surface of its epithelium

A

Corynebacterium diphtheriae

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32
Q

C. diphtheriae secretes an AB toxin: the B subunit binds to tracheal cells, the A subunit enters the cytosol and ADP ribosylates

A

EF-2

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33
Q

Essential for the translocation step in protein synthesis and blocks protein synthesis

A

Elongation Factor 2 (EF-2)

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34
Q

C. diphtheriae forms black colonies on selective

-Cells are Gram-positive rods, in smears often in V- or L-shaped pairs

A

Tellurite Agar

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35
Q

The DTP vaccine contains

A

Diptheria toxoid

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36
Q

Multiply intracellularly - cell-mediated immunity plays the major role in defense

A

Mycobacteria

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37
Q

Because of their lipid-rich envelopes, they are highly resistant to heat, cold, and drying, can persist for long times in the environment, and require high-level disinfection for killing

A

Mycobacteria

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38
Q

What are the three species of mycobacteria that are highly pathogenic for humans?

A

M. Tuberculosis, M. bovis, and M. Leprae

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39
Q

Exclusively a human pathogen, transmitted by the respiratory route.

-Not strikingly contagious, transmission requires prolonged close contact

A

M. tuberculosis (MTB)

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40
Q

Primary infections occur by inhalation of respiratory droplets

A

MTB

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41
Q

Infection develops at foci in well-aerated parts of the lung

-Acute inflammation develops at these sites and bacteria spread to local lymph nodes

A

MTB

42
Q

Occurs at the initial foci and lymph nodes, forming the ‘tubercules’ [= small lumps] for which the disease is named

A

Granulomatous inflammation

43
Q

A granuloma is a site of persistent cell-mediated inflammation. The chief inflammatory cells are macrophages. The exterior of the lesion contains

A

Mononuclear cells and fibroblasts

44
Q

The center of the lesion becomes necrotic and the periphery fibrotic and ultimately calcified. These calcified lesions are the spots picked up by

A

Chest X-ray

45
Q

If a cavity erodes into an airway, exudate from the lesion, containing bacteria, is coughed up, and the person becomes

A

Infectious to others

46
Q

Active tuberculosis is a chronic, slowly progressive disease. The characteristic cachexia [weight loss] is thought to produced by cytokines released by activated

A

Macrophages and T lymphocytes

47
Q

TB can present as a disease of any

A

Organ

48
Q

Prevents healing of primary lesions so infection proceeds directly to cavitary and/or disseminated disease

A

Defective cell-mediated immunity

49
Q

Chronic fever and weight loss, Bloody sputum [hemoptysis]. and Chest pain are symptoms of

A

MTB

50
Q

Which three laboratory tests do we want to order, in order of speed, if we suspect TB?

A

Acid-fast stain, chest x-ray, and skin test

51
Q

In the classic acid-fast technique the red dye carbol-fuchsin is caused to penetrate the cells by

A
  1. ) Heat (Ziehl-Neelsen)

2. ) Detergent (Kinyoun)

52
Q

After de-colorizing with acid alcohol, a blue or green counterstain is applied; bacteria appear

A

Brilliant Red

53
Q

Most labs now use a fluorescent dye [such as Auramine O]: this improves contrast and allows slides to be scanned at

A

Lower power

54
Q

With auramine O, bacteria apear

A

Yellow against a black background

55
Q

Presence of more than one acid-fast bacterium is considered significant in a

A

Sputum smear

56
Q

Tuberculin testing detects the cell-mediated immune response to

A

MTB

57
Q

The current gold-standard for TB testing is the

A

Mantoux test

58
Q

In immunocompetent persons induration of more than 10 mm is taken as

A

Positive

59
Q

This demonstrates prior infection with M. tuberculosis but not necessarily active disease. A person becomes tuberculin-positive only

A

1-2 months after ifnection

60
Q

Patients with advanced tuberculosis may be tuberculin-negative , i.e.

A

Anergic

61
Q

A tuberculin test does not provide enough antigen to cause conversion to a tuberculin-positive state, but it is sufficient to ‘boost’

A

Pre-existing immunity

62
Q

Sputum cultures for TB grow slow. Colonies maynot appear for 3-4 weeks, and cultures are considered negative only after

A

8 weeks of incubation

63
Q

What is the standard solid media for TB sputum culturing?

A

Lowenstein-Jensen and Middlebrook agars

64
Q

Both contain antibiotics and the dye malachite green to inhibit other bacteria and fungi

A

Lowenstein-Jensen and Middlebrook agars

65
Q

Prefer fatty acids as a carbon/energy source and a source of these is added (for example, egg yolk)

A

Mycobacteria

66
Q

Results are often positive in 7-14 days, faster than standard culture

A

BACTEC system

67
Q

The BACTEC system relies on the ability of mycobacteria to metabolize

A

Long-chain fatty acids

68
Q

The BACTEC system can be used to determine

A

Antibiotic sensitivity

69
Q

Causes disease by virtue of its ability to cause intense inflammation and persist in the face of it.

-It can multiply within macrophages and kill them

A

M. tuberculosis

70
Q

Attention has focused on MTB’s lipid-rich impermeable envelope. It contains high molecular weight polysaccharides, some of which are covalently-linked to

A

Peptidoglycan

71
Q

Polysaccharides heavily substituted with long-chain mycolic acids, long-chain branched fatty acids containing 60-90 carbon atoms, are thought to form an “outer membrane” of MTB, analogous to that of

A

Gram-negative bcteria

72
Q

Virulent mycobacteria grow in

A

Serpentine cords

73
Q

This is associated with presence in the envelope of

A

‘Cord factor” (Trehalose dimycolate)

74
Q

Toxic to phagocytes and other cells and antibody to it is protective

A

Cord Factor

75
Q

A fraction prepared from the envelope of MTB that contains lipid, polysaccharide, and fragments of peptidoglycan; it is highly stimulatory to the immune system, especially to TH cells

A

Wax D

76
Q

Ability of macrophages to kill mycobacteria depends on their activation by

A

TH1 cytokines

77
Q

The primary drug for treatment of tuberculosis.

  • Inhibits mycolic acid synthesis
  • Prophylaxis for recent converters to tuberculin-positive status, for 6-12 months
A

Isoniazid (INH)

78
Q

Must be converted to an active form by a bacterial enzyme, catalase/peroxidase

A

INH

79
Q

INH-resistant mycobacteria lose this enzyme activity by mutation, and maintain resistance to oxidants by overproduction of a second enzyme, a

A

Hydroperoxidase

80
Q

Analogue of nicotinic acid.

-Active only against TB, not other mycobacteria

A

Pyrazinamide (PZA)

81
Q

Inhibits transfer of arabinose to cell-wall polysaccharides.

-Mutations in genes encoding membrane proteins confer resistance

A

Ethambutol

82
Q

Inhibits prokaryotic ribosomes

A

Streptomycin

83
Q

Resistance to single agents arises frequently in M. tuberculosis but appearance of resistant strains is prevented by

A

Multiple Drug Regimens

84
Q

Multiply-resistant strains are thought to arise through successive mutations. Failure to follow a treatment regimen may allow emergence of a strain resistant to

A

One Drug

85
Q

“Multi-resistant’ strains of MTB are defined as those resistant at least to

A

INH and RIF

86
Q

Many TB patients in the U.S. are alcoholic, drug-addicted, or homeless, and in the face of such problems compliance with treatment plans is often poor and drug-resistance is common. In such groups, what is recommended?

A

Directly-Observed Therapy (DOT)

87
Q

An attenuated strain of M. bovis, used as a vaccine in many countries

A

‘Bacillus of Calmette and Guerin’ [BCG]

88
Q

Its use reduces TB cases by about 75%. It does not prevent infection but does prevent progression to active disease

A

BCG vaccine

89
Q

Divides mycobacteria into four groups, based on pigment synthesis and growth rate

A

The Runyon Classification

90
Q

Runyon group I are slow growers that pigment only when grown in light (photochromogens). The important species are

A

M. marinum and M. Kansasii

91
Q

Runyon group II are slow growers that pigment when grown in either light or dark. The important species are

A

M. avium and M. Intracellulare

92
Q

Inhabits fresh or salt water. Infections follow skin trauma, produce local ulceration and/or nodules that progress up the local lymphatics

A

M. marinum

93
Q

Tend to occur in people who engage in boating or water sports, or who keep aquaria [“fish-tank granulomas”]

A

M. marinum infections

94
Q

Widespread, especially in the SE U.S., where up to 80% of the population is skin-test positive

A

The M. avium/M. intracellulare complex [MAI]

95
Q

Common in AIDS patients in whom it proceeds directly to disseminated disease

A

MAI infection

96
Q

Resistant to most anti-TB drugs

A

MAI

97
Q

Its temperature optimum is below body temperature, so it grows best in the cooler parts of the body.

-In vivo its doubling time is about two weeks

A

M. Leprae

98
Q

Arise from the tropism of M. leprae for Schwann cells

A

Peripheral neuropathy and sensory loss

99
Q

The inflammatory response of the host is responsible for the nerve and tissue damage which occur over years of

A

M. Leprae infection

100
Q

Immunity dominated by a TH1 response leads to

-lesions are few and circumscribed and contain small numbers of bacteria

A

Tuberculoid disease

Microbiology Lecture Slides (24 decks)

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