Mechanisms of Antimicrobial Action and Resistance 2 Flashcards Preview

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Flashcards in Mechanisms of Antimicrobial Action and Resistance 2 Deck (76):
0

What does vancomycin do? Is it a different mechanism than penicillin?

Inhibits peptidoglycan synthesis
Yes

1

What does vancomycin bind to?

D Ala - D Ala substrate

2

Is vancomycin resistant to beta-lactamases?

Yes

3

Vancomycin: depsipentapeptide vs pentapeptide

Pentapeptide is vancomycin sensitive (binds to D alanyl - D alanine)
Depsipentapeptide is vancomycin resistant (can't bind to D alanyl - D lactate)

4

What did vancomycin used to be considered as?

Last resort

5

Vancomycin resistant bacteria do what?

Synthesize D-Ala - Lactate substrate and the depsipentapeptide
Destroy the D-Ala - D-Ala substrate and pentapeptide

6

What is single-gene resistance used for?

Screening

7

The bla gene encodes what?

Beta-lactamase enzyme

8

mecA gene encodes what?

PBP 2A - methicillin resistance

9

How many separate van genes are there?

5 - multiple gene resistance

10

Drugs that act on ribosomes do what?

Act on subunits of bacterial ribosome to disrupt translation

11

What do aminoglycosides do?

Affect the 30S subunit of ribosomes and are bactericidal (gram positives and negatives)

12

What does tetracycline do?

Affects 30S subunit and is bacteriostatic

13

Which drugs affect the 50S subunit?

Chloramphenicol, macrolides, clindamycin
Bacteriostatic

14

Gentamicin (aminoglycoside) inhibits what?

30S ribosomal subunit and mitochondrial ribosomes

15

What acts as a barrier to gentamicin?

Mammalian cells and mitochondrial membranes

16

Mechanism of resistance to gentamicin?

Proteins modify and inactivates gentamicin and other aminoglycosides
Resistance is additive
Proteins encoded on plasmids

17

Can there be resistant ribosomal proteins?

Its very rare but when it happens it is highly resistant

18

Types of kanamycin inactivation?

N-acetyl transferases
O-acetyl transferases
O-adenyl transferases
O-phosphatases

19

Chloramphenicol binds to what, inhibits and does not inhibit what?

Binds to 50S
Inhibits mitochondrial 70S
Does not inhibit mammalian 80S

20

Chloramphenicol can cause what, in what percent of cases?

Aplastic anemia in 1/25k-40k administrations

21

Erythromycin is what type of antibiotic?

Macrolide

22

Erythromycin inhibits, doesn't inhibit, doesn't cross?

Does not inhibit mammalian 80S
Inhibits mitochondrial 70S
Doesn't cross mitochondrial membrane

23

Mechanism of resistance to erythromycin?

Resistance by rRNA methylation

24

Erythromycin is often used as an alternative to what?

Penicillin because of allergies

25

Clindamycin has a similar spectrum as what? Binds to what?

Binds to 50S
similar spectrum as erythromycin

26

Clindamycin is frequently associated with what?

Bowel superinfection with clostridium difficile colitis
AKA pseudomembranous colitis

27

What is clindamycin used for?

Used to treat anaerobic infections

28

What are tetracyclines?

Bacteriostatic inhibitors with broad spectrum

29

What are tetracycline mechanism of action?

Block binding of aminoacyl-tRNAs to A site of 30S

30

Resistance to tetracyclines due to what?

Efflux and insensitive ribosomes

31

Quinupristin/Dalfopristin do what?

Act synergistically on the ribosome to prevent protein synthesis

32

Quinupristin/Dalfopristin are active against what?

VRSA and VRE (E. faecium not E. faecalis)

33

Quinupristin/Dalfopristin used often? Why?

No, lots of side effects and must be given IV

34

Linezolid (zyvox) mechanism of action? What bacteria does it work against?

Inhibits protein synthesis at the ribosome
Bacteriostatic against staphylococci and enterococci, VRSA and VRE (E. faecium not E. faecalis)

35

Linezolid (zyvox) is administered how? How is it tolerated?

Orally or IV
Generally well-tolerated

36

Telithromycin (ketek) is structurally related to what?

Macrolides, which include erythromycin

37

How does telithromycin work? Treats what?

Blocks protein synthesis
Treats gram positive staph aureus (not VRSA) and s. pneumoniae

38

Telithromycin (ketek) problem?

Reports of serious hepatotoxicity

39

Tigecycline (Tygacil) is active against what?

MRSA and probably VRE in vitro

40

Is tigecycline (tygacil) broad spectrum?

Yes

41

Is tigecycline a substrate for tetracycline antiporters?

No

42

What is tigecycline approved to treat? Administration?

Complicated intra-abdominal and skin suture infections.
IV, bacteriostatic

43

Nystatin binds to what?

Binds to ergosterol (found in fungi membranes)

44

Nystatin mechanism of action?

Forms pores, leading to potassium efflux, depolarization, and cell death

45

Nystatin used to treat what?

Mold and yeast infections

46

Polymyxins effective against what gram?

Gram negative but not gram positive
Bactericidal, affecting outer membrane

47

Polymyxins are used as what?

Topical creams because they are too toxic for systemic use

48

Daptomycin (cubicin) is what?

lipopeptide

49

Daptomycin: how does it work, what is it effective against?

Binds to membrane of gram positives and depolarizes it
Effective against VRSA and VRE

50

How is daptomycin administered and what is it approved for?

IV
Treatment of complicated skin and skin suture infections

51

What is sulfanilamide?

First sulfonamide discovered 4 years after penicillin (1932)
Red dye that cured strep/staph in mice

52

Sulfonamide antagonizes what?

para-aminobenzoic acid (PABA)

53

Sulfonamides vs PABA (compete for uptake by bacteria)

PABA is 1000 times more effective
Small amounts PABA negate sulfonamides
Not a problem because we don't get a lot of PABA in our diets and it is rapidly excreted

54

We lack dihydropteroic acid synthase, so we require what in our diet?

Folic acid

55

How are bacteria different from humans when it comes to folic acid?

Bacteria must synthesize it with dihydropteroic acid synthase
They can't use an external source

56

Are sulfonamides effective in the presence of folic acid?

Yes

57

What happens when sulfonamides are used?

There is a deficit in tetrahydrofolic acid

58

Sulfonamides bacteriostatic or bactericidal?

They are bacteriostatic if they block RNA/protein synthesis
They are bactericidal if RNA/protein synthesis continues (if there are methionine and purines in the environment such as in blood or urine)

59

Why are sulfonamides ineffective in purulent lesions?

Rich in methionine, purines, and thymidine from lysed cells so RNA/DNA/protein synthesis can continue

60

Sulfonamides introduced the problem of what?

Bacterial resistance to drugs

61

Sulfonamides were introduced to treat what?

Bacterial dysentery in WWII

62

How many years did it take for bacteria to become resistant to sulfonamides?

4 years
And about 10% of cases were resistant to other drugs

63

True/False: resistance to multiple drugs is more common than resistance to a single drug. Why?

True
R factors (transposons) carry multiple resistance genes

64

What are three mechanisms of resistance to sulfonamides?

Reduced uptake (antiporter)
Altered dihydropteroic acid synthase
Increased synthesis of PABA (rare)

65

Trimethoprim: what does it do?

Trimethoprim blocks a step in biosynthesis of tetrahydrofolic acid
It is a competitive inhibitor of dihydrofolic acid reductase

66

Trimethoprim is a competitive inhibitor of dihydrofolate reducate: do humans or bacteria have this?

Both humans and bacteria have dihydrofolate reductase

67

If humans have dihydrofolate reductase, which trimethoprim is a competitive inhibitor for, how is it ok for us to use it?

The human dihydrofolate reductase is 60k fold less sensitive to trimethoprim than the bacterial dihydrofolate reductase

68

Resistance to trimethoprim?

Dihydrofolate reductases with reduced sensitivity to trimethoprim
It is not a mutant form of the bacterial enzyme, but a new gene

69

How do sulfonamides and trimethoprim work together?

They are synergistic, meaning you can use smaller doses.
Use of the drugs together (5 parts sulfamethoxazole: 1 part trimethoprim) reduces the frequency of resistance

70

What is bactrim?

5 parts sulfamethoxazole: 1 part trimethoprim

71

Which drug was the first quinolone?

Naldixic

72

Naldixic was used for what?

Treatment of UTIs
Rapidly excreted in urine but too toxic for systemic use

73

How does naldixic work?

Inhibits A subunit of DNA gyrase - rapidly inhibits DNA synthesis
The human analog (topoisomerase II) is several hundred fold less sensitive
Bactericidal unless growth is prevented

74

What are three mechanisms of resistance to quinolones?

Missense mutations in DNA gyrase subunit A
Reduced uptake
Plasmid-encoded resistance genes that reverses the inhibition of DNA gyrase subunit A

75

Ciprofloxacin (a quinolone) resistance stats in nosocomial infections
Why did resistance increase so quickly?

Between 1989 and 1992 resistance among S. aureus increased 123%
1/4 of all S. aureus were resistant
Drug was used at levels close to MIC