Lecture 17 - Antimicrobials III Flashcards

1
Q

Antimicrobials that bind to 30s ribosomal subunit

A

Aminogycosides, tetracyclines

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2
Q

Antimicrobials that target 50s ribosomal subunit

A

Chloramphenicol, macrolides

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3
Q

What does chloramphenicol target?

A

Peptidyl transfer

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4
Q

What do macrolides target?

A

Translocation

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5
Q

What does mupirocin target?

A

Isoleucyl tRNA synthesis

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6
Q

What do oxazolidones target?

A

Formation of initiation complex

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7
Q

What was the first aminoglycoside?

A

Streptomycin

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8
Q

What is tobramycin good for?

A

Treating pseudomonas

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9
Q

What is gentamicin good for?

A

A general-purpose anti-G- antimicrobial

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10
Q

Why do aminoglycosides need to be injected?

A

Not absorbed through epithelium, so if ingested would only be active in the GIT

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11
Q

How are aminoglycosides administered?

A

injected

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12
Q

Are aminoglycosides bacteriostatic or bactericidal?

A

Bactericidal

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13
Q

Stages of aminoglycodside bactericidal action
1)
2)

A

1) Binds 30s subunit, makes recognition of mRNA codons defective. Abnormal proteins form.
2) Abnormal proteins cause membrane to become more permeable. More aminoglycosides enter bacterium, cause complete ribosomal blockade

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14
Q

Why does a small amount of aminoglycoside initially enter a bacterium?

A

Aminoglycosides are lipid-insoluble.

Have difficulty passing through cell membrane, cell wall

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15
Q

What is a benefit of amikacin?

A

Resistant to a lot of enzymes which modify aminoglycosides, so as to inactivate them

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16
Q

Three types of bacteria, with respect to growth under streptomycin

A

1) StrS - Susceptible
2) StrR - Resistant
3) StrD - Dependent

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17
Q

Why are StrD bacteria dependent on aminoglycoside presence?

A

Ribosomes are defective. Aminoglycosides correct this defect.

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18
Q

Ways that aminoglycosides are modified by bacteria
1)
2)
3)

A

1) Phosphorylation
2) Adenylation
3) Acetylation

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19
Q
Methods of microbial resistance to aminoglycosides
1)
2)
3)
4)
A

1) Efflux
2) Modified outer membrane leading to reduced entry
3) Enzymatic modification of aminoglycoside, leading to reduced entry
4) Modified 30s subunit

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20
Q

Example of resistance by drug inactivation
1)
2)

A

1) Beta lactams by beta lactamases (hydrolysis)

2) Covalent modification - aminoglycosides, chloramphenicol

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21
Q

Example of resistance by altering target of drug
1)
2)

A

1) Modify target to a less-sensitive form - Beta-lactams, vancomycin
2) Overproduce target - Vancomycin

22
Q

Example of resistance by reducing drug access to target
1)
2)

A

1) Reduced entry into a cell - Aminoglycosides

2) Increased efflux from a cell - Aminoglycosides, tetracycline

23
Q

Example of resistance by failing to activate drug precursor
1)
2)

A

1) Metronidazole

2) Isoniazid

24
Q

How is metronidazole activated?

A

Is reduced in hydrogenosome

25
Q

What is metronidazole effective aginst?

A

Obligate anaerobes

26
Q

Examples of organisms susceptible to metronidazole

A

Giardia, entamoeba, trachomatis

27
Q

Bacteria resistant to carbapenems

A

Enterobacteriaceae

28
Q

Examples of innate resistance
1)
2)
3)

A

1) Mycoplasma - lack cell wall
2) Cell wall impenetrability (G- resistant to vancomycin)
3) Pseudomonas - beta-lactam resistance gene on chromosome

29
Q

Two cycles of phage infection

A

1) Temperate cycle - gene integrates into genome, cell isn’t lysed
2) Lytic cycle

30
Q

Example of bacterium with temperate cycle bacteriophage DNA

A

Vibrio cholerae, with choleratoxin gene from a phage

31
Q

Difference in ability to share genetic information between conjugation and transformation

A

Transformation requires that bacteria are closely-related

Conjugation can occur between unrelated bacteria (even between G+ and G- bacteria)

32
Q

Most important type of bacterial horizontal transfer

A

Plasmid-mediated

33
Q

Ways to test bacterial antimicrobial resistance
1)
2)

A

1) Dilution tests

2) Diffusion tests

34
Q

What do minimum inhibitory concentration tests test?

A

Bacteriostatic action

35
Q

How do you test bactericidal action from a MIC test?

A

Take samples from inhibited samples, culture them on a gel without antimicrobials. See which grow.
This gives MBC (minimum bactericidal concentration)

36
Q

MIC test
1)
2)

A

1) Doubling dilutions of antimicrobial of interest

2) Add bacteria of interest, see which grow, which are inhibited

37
Q

Potential problems with dilution tests
1)
2)

A

1) Takes up space. If have to test many samples, can quickly run out of room in lab
2) Patient samples often contain several bacterial species

38
Q

Solution to issues with dilution tests

A

Use diffusion tests

Disc susceptibility test

39
Q

Advantages of disc susceptibility test

A

Can test several different antimicrobials at once (each on a different disc), on the one plate

40
Q

Drawbacks of disc susceptibility test

A

Can’t directly compare diameters of inhibition, as different antimicrobials have different rates of diffusion

41
Q

Two types of antibiotic susceptibility data

A

1) Two distinct populations on graph - Beta-lactamase

2) Continuous gradient of susceptibility - Altered penicillin-binding proteins

42
Q

Break-points for pneumococci

A

Fully-susceptible MIC 1mg/L

43
Q

How to determine disc susceptibility breakpoints

A
Chart MIC (from dilution test) for different bacteria on a graph
On same axes, for the same bacteria, chart disc susceptibility test zone diameter.

Negative correlation between MIC and width of zone diameter

44
Q

Two types of error in testing with MIC and disc susceptibility

A

1) False susceptible

2) False resistant

45
Q

Worse type of error

A

False susceptible

Results in patient being given an antimicrobial that isn’t effective

46
Q

Less severe type of error

A

False resistant

Results in patient being denied an effective antibiotic, but given a similarly effective one instead

47
Q

What is a false susceptible result?

A

When there is a high MIC, but large zone diameter.
MIC correctly reflects bacterial susceptibility.
Will result in an ineffective antimicrobial testing as efective

48
Q

What is a false resistant result?

A

When there is a low MIC, but a small zone diameter.
MIC correctly reflects bacterial susceptibility
Will result in an effective antimicrobial testing as ineffetive

49
Q

Acceptable error for false susceptible

A

Under 1%

50
Q

Acceptable error for false resistant

A

Under 4%

51
Q

Drawbacks of E test strip

A

Expensive, because under intellectual property