Lecture 17 - Antimicrobials III

Question 1

Antimicrobials that bind to 30s ribosomal subunit

Answer 1

Aminogycosides, tetracyclines

Question 2

Antimicrobials that target 50s ribosomal subunit

Answer 2

Chloramphenicol, macrolides

Question 3

What does chloramphenicol target?

Answer 3

Peptidyl transfer

Question 4

What do macrolides target?

Answer 4

Translocation

Question 5

What does mupirocin target?

Answer 5

Isoleucyl tRNA synthesis

Question 6

What do oxazolidones target?

Answer 6

Formation of initiation complex

Question 7

What was the first aminoglycoside?

Answer 7

Streptomycin

Question 8

What is tobramycin good for?

Answer 8

Treating pseudomonas

Question 9

What is gentamicin good for?

Answer 9

A general-purpose anti-G- antimicrobial

Question 10

Why do aminoglycosides need to be injected?

Answer 10

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

Question 11

How are aminoglycosides administered?

Answer 11

injected

Question 12

Are aminoglycosides bacteriostatic or bactericidal?

Answer 12

Bactericidal

Question 13

Stages of aminoglycodside bactericidal action
1)
2)

Answer 13

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

Question 14

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

Answer 14

Aminoglycosides are lipid-insoluble.

Have difficulty passing through cell membrane, cell wall

Question 15

What is a benefit of amikacin?

Answer 15

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

Question 16

Three types of bacteria, with respect to growth under streptomycin

Answer 16

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

Question 17

Why are StrD bacteria dependent on aminoglycoside presence?

Answer 17

Ribosomes are defective. Aminoglycosides correct this defect.

Question 18

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

Answer 18

1) Phosphorylation
2) Adenylation
3) Acetylation

Question 19

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

Answer 19

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

Question 20

Example of resistance by drug inactivation
1)
2)

Answer 20

1) Beta lactams by beta lactamases (hydrolysis)

2) Covalent modification - aminoglycosides, chloramphenicol

Question 21

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

Answer 21

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

Question 22

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

Answer 22

1) Reduced entry into a cell - Aminoglycosides

2) Increased efflux from a cell - Aminoglycosides, tetracycline

Question 23

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

Answer 23

1) Metronidazole

2) Isoniazid

Question 24

How is metronidazole activated?

Answer 24

Is reduced in hydrogenosome

Question 25

What is metronidazole effective aginst?

Answer 25

Obligate anaerobes

Question 26

Examples of organisms susceptible to metronidazole

Answer 26

Giardia, entamoeba, trachomatis

Question 27

Bacteria resistant to carbapenems

Answer 27

Enterobacteriaceae

Question 28

Examples of innate resistance 1) 2) 3)

Answer 28

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

Question 29

Two cycles of phage infection

Answer 29

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

Question 30

Example of bacterium with temperate cycle bacteriophage DNA

Answer 30

Vibrio cholerae, with choleratoxin gene from a phage

Question 31

Difference in ability to share genetic information between conjugation and transformation

Answer 31

Transformation requires that bacteria are closely-related Conjugation can occur between unrelated bacteria (even between G+ and G- bacteria)

Question 32

Most important type of bacterial horizontal transfer

Answer 32

Plasmid-mediated

Question 33

Ways to test bacterial antimicrobial resistance 1) 2)

Answer 33

1) Dilution tests | 2) Diffusion tests

Question 34

What do minimum inhibitory concentration tests test?

Answer 34

Bacteriostatic action

Question 35

How do you test bactericidal action from a MIC test?

Answer 35

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

Question 36

MIC test 1) 2)

Answer 36

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

Question 37

Potential problems with dilution tests 1) 2)

Answer 37

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

Question 38

Solution to issues with dilution tests

Answer 38

Use diffusion tests | Disc susceptibility test

Question 39

Advantages of disc susceptibility test

Answer 39

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

Question 40

Drawbacks of disc susceptibility test

Answer 40

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

Question 41

Two types of antibiotic susceptibility data

Answer 41

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

Question 42

Break-points for pneumococci

Answer 42

Fully-susceptible MIC 1mg/L

Question 43

How to determine disc susceptibility breakpoints

Answer 43

``` 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

Question 44

Two types of error in testing with MIC and disc susceptibility

Answer 44

1) False susceptible | 2) False resistant

Question 45

Worse type of error

Answer 45

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

Question 46

Less severe type of error

Answer 46

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

Question 47

What is a false susceptible result?

Answer 47

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

Question 48

What is a false resistant result?

Answer 48

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

Question 49

Acceptable error for false susceptible

Answer 49

Under 1%

Question 50

Acceptable error for false resistant

Answer 50

Under 4%

Question 51

Drawbacks of E test strip

Answer 51

Expensive, because under intellectual property