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Flashcards in Intro to antibacterial agents Deck (44):
1

What is meant by bacteristatic?

Antibiotics that inhibit bacterial growth, ie protein synthesis inhibitors.

2

What is meant by bactericidal?

Antibiotics that kill bacteria, ie cell wall-active agents

3

What is the minimum inhibitory concentration?

Minimum concentration of antibiotic at which visible growth is inhibited.

4

What is antimicrobial synergism?

Activity of two antimicrobials given together is greater than the sum of their activity if given separately.

5

Give a clinical example of synergism.

β-lactam/aminoglycoside combination therapy of streptococcal endocarditis.

6

What are possible antibiotic targets?

-Cell wall
-Protein synthesis
-DNA synthesis
-RNA synthesis
-Plasma membrane

7

What is the bacterial cell wall made of?

Peptidoglycan - Polymer of glucose-derivatives, N-acetyl muramic acid (NAM) and N-acetyl glucosamine (NAG)

8

Give example of antibiotics that inhibit cell wall synthesis.

β-lactams
Glycopeptides

(also cycloserine and fosfomycin)

9

Why are the beta-lactam antibiotics so-called?

Because they have a beta -lactam ring structure.

10

What was the first beta-lactam antibiotic?

Benzylpenicillin (penicillin G). Acid labile so must be delivered parenterally.

11

What was the first oral antibiotic?

Phenoxymethylpenicillin (penicillin V)

12

Describe the beta lactam ring

Four members - CCCN

13

How do beta lactams work?

Interfere with function of “penicillin binding proteins” - transpeptidases enzymes involved in the peptideoglycan cross-linking.

14

Give examples of classes of beta lactams.

Penicillins (relatively narrow spectrum), cephalosporins, carbapenems, monobactams (broad spectrum).

15

What kind of ribosomes do bacteria possess?

70s (30s+50s)

16

How do aminoglycosides such as gentamicin inhibit protein synthesis?

-Bind to 30S ribosomal subunit
-Mechanism of action not fully understood

17

How to macrolides (erythromycin), lincosamides (clindamycin) and the streptogramins work?

-Bind to 50S ribosomal subunit
-Blockage of exit tunnel
-Inhibit protein elongation

18

How do tetracyclines inhibit protein synthesis?

-Bind to 30S ribosomal subunit
-Inhibit RNA translation
-Interfere with binding of tRNA to rRNA

19

How do oxazolidinones inhibit protein synthesis?

-Inhibits initiation of protein synthesis
-Binds to 50S ribosomal subunit
-Inhibits assembly of initiation complex
-May also bind to 70S subunit

20

How do trimethoprim and the sulfonamides inhibit DNA synthesis.

-Inhibit folate synthesis - folic acid is a purine synthesis precursor
-Trimethoprim inhibits dihydrofolate reductase
-Sulfonamides inhibit dihydropteroate synthetase

21

How do the quinolones and flouroquinolones (ciprofloxacin) inhibit DNA synthesis?

Inhibit one or more of two related enzymes -DNA gyrase and topoisomerase IV

Involved in remodelling of DNA during DNA replication
Supercoiling/strand separation

22

How do RNA synthesis inhibitors like rifampicin work?

-RNA polymerase inhibitor
-Prevents synthesis of mRNA

23

How does the plasma membrane agent daptomycin work?

- Cyclic lipopeptide
- Inserts lipophilic tail into cell membrane resulting in depolarisation and ion loss
- Effective in Gram-positives only

24

What are the specific adverse effects associated with aminogylcosides?

-Reversible renal impairment on accumulation
-Therapeutic drug monitoring indicated

25

What are the main adverse effects of beta lactams?

- Main problems are allergic reactions
- Generalised rash 1-10%
- Anaphylaxis approx. 0.01%

26

What is the main adverse effect of linezolid?

Bone marrow depression

27

What factors are responsible for the clinical features and transmissability of C.diff infection?

Combination of enterotoxin (A and B) and spore production.

28

What is the assumed cause of C.diff infection?

Abolition of colonisation resistance (normal flora?).

29

What is the designation of the hypervirulent strain of C.diff?

027

30

What are the common precipitating antibiotics for C.diff?

- Cephalosporins
- Ciprofloxacin (esp. ribotype 027)
- Clindamycin
(may be precipitated by any antibiotic)

31

What are the less common precipitating antibiotics for C.diff?

- Benzylpenicillin
- Aminoglycosides
- Glycopeptides
- Piperacillin-tazobactam

32

What is empiric therapy?

Based on predicted susceptibility of likely pathogens and local policies.

33

What is targeted therapy?

Based on predicted susceptibility on infecting orginisms and local policy.

34

What is susceptibility-guided therapy?

Based on susceptibility testing results.

35

What bacteria is flucloxacillin most commonly used for

S. aureus

36

What bacteria is benzylpenicillin most commonly used for?

S. pyogenes

37

What are cephalosporins used for?

Gram -ve

38

What is metrindazole used for?

Anaerobes

39

What is vancomycin used for?

Gram +ve - MRSA

40

In what bodily fluid do beta lactams show good availability in the presence of inflammation?

CSF

41

Which antibiotics do not show good availability in CSF?

Aminoglycosides and vancomycin

42

Which antibiotics show good availability in urine?

Trimethoprim and β-lactams

43

Which antibiotics show poor availability in urine?

MLS Abx

44

What are the reasons for combining antibiotics?

1. To increase efficacy
- Synergistic combination may improve outcome

2. To provide adequately broad spectrum
- Single agent may not cover all required organisms
- Empiric treatment of sepsis
3. To reduce resistance
- Organism would need to develop resistance to multiple agents simultaneously
- Antituberculous chemotherapy

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