Lecture 17 - Antimicrobials III Flashcards Preview

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Flashcards in Lecture 17 - Antimicrobials III Deck (51):
1

Antimicrobials that bind to 30s ribosomal subunit

Aminogycosides, tetracyclines

2

Antimicrobials that target 50s ribosomal subunit

Chloramphenicol, macrolides

3

What does chloramphenicol target?

Peptidyl transfer

4

What do macrolides target?

Translocation

5

What does mupirocin target?

Isoleucyl tRNA synthesis

6

What do oxazolidones target?

Formation of initiation complex

7

What was the first aminoglycoside?

Streptomycin

8

What is tobramycin good for?

Treating pseudomonas

9

What is gentamicin good for?

A general-purpose anti-G- antimicrobial

10

Why do aminoglycosides need to be injected?

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

11

How are aminoglycosides administered?

injected

12

Are aminoglycosides bacteriostatic or bactericidal?

Bactericidal

13

Stages of aminoglycodside bactericidal action
1)
2)

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

14

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

Aminoglycosides are lipid-insoluble.
Have difficulty passing through cell membrane, cell wall

15

What is a benefit of amikacin?

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

16

Three types of bacteria, with respect to growth under streptomycin

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

17

Why are StrD bacteria dependent on aminoglycoside presence?

Ribosomes are defective. Aminoglycosides correct this defect.

18

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

1) Phosphorylation
2) Adenylation
3) Acetylation

19

Methods of microbial resistance to aminoglycosides
1)
2)
3)
4)

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

20

Example of resistance by drug inactivation
1)
2)

1) Beta lactams by beta lactamases (hydrolysis)
2) Covalent modification - aminoglycosides, chloramphenicol

21

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

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

22

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

1) Reduced entry into a cell - Aminoglycosides
2) Increased efflux from a cell - Aminoglycosides, tetracycline

23

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

1) Metronidazole
2) Isoniazid

24

How is metronidazole activated?

Is reduced in hydrogenosome

25

What is metronidazole effective aginst?

Obligate anaerobes

26

Examples of organisms susceptible to metronidazole

Giardia, entamoeba, trachomatis

27

Bacteria resistant to carbapenems

Enterobacteriaceae

28

Examples of innate resistance
1)
2)
3)

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

29

Two cycles of phage infection

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

30

Example of bacterium with temperate cycle bacteriophage DNA

Vibrio cholerae, with choleratoxin gene from a phage

31

Difference in ability to share genetic information between conjugation and transformation

Transformation requires that bacteria are closely-related

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

32

Most important type of bacterial horizontal transfer

Plasmid-mediated

33

Ways to test bacterial antimicrobial resistance
1)
2)

1) Dilution tests
2) Diffusion tests

34

What do minimum inhibitory concentration tests test?

Bacteriostatic action

35

How do you test bactericidal action from a MIC test?

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

36

MIC test
1)
2)

1) Doubling dilutions of antimicrobial of interest
2) Add bacteria of interest, see which grow, which are inhibited

37

Potential problems with dilution tests
1)
2)

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

Solution to issues with dilution tests

Use diffusion tests
Disc susceptibility test

39

Advantages of disc susceptibility test

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

40

Drawbacks of disc susceptibility test

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

41

Two types of antibiotic susceptibility data

1) Two distinct populations on graph - Beta-lactamase
2) Continuous gradient of susceptibility - Altered penicillin-binding proteins

42

Break-points for pneumococci

Fully-susceptible MIC 1mg/L

43

How to determine disc susceptibility breakpoints

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

Two types of error in testing with MIC and disc susceptibility

1) False susceptible
2) False resistant

45

Worse type of error

False susceptible
Results in patient being given an antimicrobial that isn't effective

46

Less severe type of error

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

47

What is a false susceptible result?

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

What is a false resistant result?

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

Acceptable error for false susceptible

Under 1%

50

Acceptable error for false resistant

Under 4%

51

Drawbacks of E test strip

Expensive, because under intellectual property