Antimycobacterial Therapies I Flashcards
1
Q
Reduces the bacillary population rapidly thereby decreasing severity of the disease, preventing death and halting transmission
A
Antituberculosis therapy
2
Q
Eradicates persisting bacilli in order to achieve durable cure (prevent relapse) after completion of therapy
A
Antituberculosis therapy
3
Q
Source of streptomycin & other antibiotics
A
Streptomyces griseus
4
Q
Indicated for multi-resistant TB, which is resistant to both isoniazid and rifampin
A
Second-line anti-TBs
5
Q
Multi-resistant TB (MDR-TB) is resistant to both
A
Isoniazid and Rifampin
6
Q
Extensively drug-resistant TB (XDR-TB) is an MDR + resistance to a
A
Fluoroquinolone and an injectable aminoglycoside
7
Q
Less effective and have significant toxic-side effects
A
Second-line anti-TBs
8
Q
Kills Mtb by targeting arabinogalactan synthesis
A
Ethambutol
9
Q
INH, ETA and PAS inhibit
A
Mycolic acid synthesis
10
Q
Inhibits DNA synthesis and supercoiling by targeting topoisomerase
A
Fluoroquinolone
11
Q
Inhibits RNA synthesis by targeting RNA polymerase
A
Rifampin
12
Q
Inhibits protein synthesis by targeting the 30S ribosomal subunit
A
Streptomycin
13
Q
Targets 23S ribosomal RNA, inhibiting peptidyl transferase
A
Macrolides
14
Q
Inhibits protein synthesis in dormant bacteria Most likely has other targets
A
Pyrazinamide
15
Q
Isoniazid, ethaionamide, and p-aminosalicylic acid inhibit
A
Mycolic acid synthesis
16
Q
Inhibits cell wall synthesis (arabinogalactan synthesis)
A
Ethambutol
17
Q
TMC-207 (bedaquiline) inhibits
A
ATP synthase
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
19
Q
4-9 months of treatment is needed for
A
TB
20
Q
How long does it take to identify resistant strains of TB?
A
3-8
21
Q
Natural resistance is always due to
A
Chromosomal mutation
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
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
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)
25
Envelopes of Mycobacterium and related genera contain long-chain
Mycolic acids
26
A non-pathogenic genus of mycobacteria, and is the source of many antibiotics
Streptomyces
27
Fungi are the commercial source of
B-lactams
28
Gram-positive rods in which the long sides of the rods are not parallel, so cells are spindle- or club-shaped
Corynebacterium
29
On smears cells often form ‘V’ or ‘W’ forms.
-The group is large and taxonomically complex and its classification changes rapidly
Corynebacterium
30
Humans are its only host; transmission is by the respiratory route
Corynebacterium diphtheriae
31
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
Corynebacterium diphtheriae
32
C. diphtheriae secretes an AB toxin: the B subunit binds to tracheal cells, the A subunit enters the cytosol and ADP ribosylates
EF-2
33
Essential for the translocation step in protein synthesis and blocks protein synthesis
Elongation Factor 2 (EF-2)
34
C. diphtheriae forms black colonies on selective
-Cells are Gram-positive rods, in smears often in V- or L-shaped pairs
Tellurite Agar
35
The DTP vaccine contains
Diptheria toxoid
36
Multiply intracellularly - cell-mediated immunity plays the major role in defense
Mycobacteria
37
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
Mycobacteria
38
What are the three species of mycobacteria that are highly pathogenic for humans?
M. Tuberculosis, M. bovis, and M. Leprae
39
Exclusively a human pathogen, transmitted by the respiratory route.
-Not strikingly contagious, transmission requires prolonged close contact
M. tuberculosis (MTB)
40
Primary infections occur by inhalation of respiratory droplets
MTB
41
Infection develops at foci in well-aerated parts of the lung
-Acute inflammation develops at these sites and bacteria spread to local lymph nodes
MTB
42
Occurs at the initial foci and lymph nodes, forming the ‘tubercules’ [= small lumps] for which the disease is named
Granulomatous inflammation
43
A granuloma is a site of persistent cell-mediated inflammation. The chief inflammatory cells are macrophages. The exterior of the lesion contains
Mononuclear cells and fibroblasts
44
The center of the lesion becomes necrotic and the periphery fibrotic and ultimately calcified. These calcified lesions are the spots picked up by
Chest X-ray
45
If a cavity erodes into an airway, exudate from the lesion, containing bacteria, is coughed up, and the person becomes
Infectious to others
46
Active tuberculosis is a chronic, slowly progressive disease. The characteristic cachexia [weight loss] is thought to produced by cytokines released by activated
Macrophages and T lymphocytes
47
TB can present as a disease of any
Organ
48
Prevents healing of primary lesions so infection proceeds directly to cavitary and/or disseminated disease
Defective cell-mediated immunity
49
Chronic fever and weight loss, Bloody sputum [hemoptysis]. and Chest pain are symptoms of
MTB
50
Which three laboratory tests do we want to order, in order of speed, if we suspect TB?
Acid-fast stain, chest x-ray, and skin test
51
In the classic acid-fast technique the red dye carbol-fuchsin is caused to penetrate the cells by
1. ) Heat (Ziehl-Neelsen)
| 2. ) Detergent (Kinyoun)
52
After de-colorizing with acid alcohol, a blue or green counterstain is applied; bacteria appear
Brilliant Red
53
Most labs now use a fluorescent dye [such as Auramine O]: this improves contrast and allows slides to be scanned at
Lower power
54
With auramine O, bacteria apear
Yellow against a black background
55
Presence of more than one acid-fast bacterium is considered significant in a
Sputum smear
56
Tuberculin testing detects the cell-mediated immune response to
MTB
57
The current gold-standard for TB testing is the
Mantoux test
58
In immunocompetent persons induration of more than 10 mm is taken as
Positive
59
This demonstrates prior infection with M. tuberculosis but not necessarily active disease. A person becomes tuberculin-positive only
1-2 months after ifnection
60
Patients with advanced tuberculosis may be tuberculin-negative , i.e.
Anergic
61
A tuberculin test does not provide enough antigen to cause conversion to a tuberculin-positive state, but it is sufficient to ‘boost’
Pre-existing immunity
62
Sputum cultures for TB grow slow. Colonies maynot appear for 3-4 weeks, and cultures are considered negative only after
8 weeks of incubation
63
What is the standard solid media for TB sputum culturing?
Lowenstein-Jensen and Middlebrook agars
64
Both contain antibiotics and the dye malachite green to inhibit other bacteria and fungi
Lowenstein-Jensen and Middlebrook agars
65
Prefer fatty acids as a carbon/energy source and a source of these is added (for example, egg yolk)
Mycobacteria
66
Results are often positive in 7-14 days, faster than standard culture
BACTEC system
67
The BACTEC system relies on the ability of mycobacteria to metabolize
Long-chain fatty acids
68
The BACTEC system can be used to determine
Antibiotic sensitivity
69
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
M. tuberculosis
70
Attention has focused on MTB's lipid-rich impermeable envelope. It contains high molecular weight polysaccharides, some of which are covalently-linked to
Peptidoglycan
71
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
Gram-negative bcteria
72
Virulent mycobacteria grow in
Serpentine cords
73
This is associated with presence in the envelope of
'Cord factor" (Trehalose dimycolate)
74
Toxic to phagocytes and other cells and antibody to it is protective
Cord Factor
75
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
Wax D
76
Ability of macrophages to kill mycobacteria depends on their activation by
TH1 cytokines
77
The primary drug for treatment of tuberculosis.
- Inhibits mycolic acid synthesis
- Prophylaxis for recent converters to tuberculin-positive status, for 6-12 months
Isoniazid (INH)
78
Must be converted to an active form by a bacterial enzyme, catalase/peroxidase
INH
79
INH-resistant mycobacteria lose this enzyme activity by mutation, and maintain resistance to oxidants by overproduction of a second enzyme, a
Hydroperoxidase
80
Analogue of nicotinic acid.
-Active only against TB, not other mycobacteria
Pyrazinamide (PZA)
81
Inhibits transfer of arabinose to cell-wall polysaccharides.
-Mutations in genes encoding membrane proteins confer resistance
Ethambutol
82
Inhibits prokaryotic ribosomes
Streptomycin
83
Resistance to single agents arises frequently in M. tuberculosis but appearance of resistant strains is prevented by
Multiple Drug Regimens
84
Multiply-resistant strains are thought to arise through successive mutations. Failure to follow a treatment regimen may allow emergence of a strain resistant to
One Drug
85
“Multi-resistant’ strains of MTB are defined as those resistant at least to
INH and RIF
86
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?
Directly-Observed Therapy (DOT)
87
An attenuated strain of M. bovis, used as a vaccine in many countries
‘Bacillus of Calmette and Guerin’ [BCG]
88
Its use reduces TB cases by about 75%. It does not prevent infection but does prevent progression to active disease
BCG vaccine
89
Divides mycobacteria into four groups, based on pigment synthesis and growth rate
The Runyon Classification
90
Runyon group I are slow growers that pigment only when grown in light (photochromogens). The important species are
M. marinum and M. Kansasii
91
Runyon group II are slow growers that pigment when grown in either light or dark. The important species are
M. avium and M. Intracellulare
92
Inhabits fresh or salt water. Infections follow skin trauma, produce local ulceration and/or nodules that progress up the local lymphatics
M. marinum
93
Tend to occur in people who engage in boating or water sports, or who keep aquaria [“fish-tank granulomas”]
M. marinum infections
94
Widespread, especially in the SE U.S., where up to 80% of the population is skin-test positive
The M. avium/M. intracellulare complex [MAI]
95
Common in AIDS patients in whom it proceeds directly to disseminated disease
MAI infection
96
Resistant to most anti-TB drugs
MAI
97
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
M. Leprae
98
Arise from the tropism of M. leprae for Schwann cells
Peripheral neuropathy and sensory loss
99
The inflammatory response of the host is responsible for the nerve and tissue damage which occur over years of
M. Leprae infection
100
Immunity dominated by a TH1 response leads to
-lesions are few and circumscribed and contain small numbers of bacteria
Tuberculoid disease
