T2 - L4 ANTIBACTERIAL AND ANTIFUNGAL AGENTS Flashcards

1
Q

what do bacteria and fungi have in common?

A
  • cell wall
  • cell membrane(s)
  • DNA
  • synthetic functions - protein synthesis
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2
Q

what are the differences in DNA between fungi and bacteria?

A

bacteria:

  • prokaryotes
  • DNA is ring like structure in cytoplasm

fungi:

  • eukaryotes
  • DNA is separated from cytoplasm by nuclear membrane
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3
Q

what are the differences in size between fungi and bacteria?

A

bacterial cells are much smaller than fungal cells

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4
Q

what do Bacteriostatic/fungistatic antimicrobials do?

A

inhibit growth

e.g. protein synthesis inhibitors

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5
Q

what do Bacteriocidal/fungicidal

antimicrobials do?

A

kill

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6
Q

what is meant by a minimum inhibitory concentration (MIC)?

A

Minimum concentration of antimicrobial agent at which visible growth is inhibited

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7
Q

what is meant by Minimum bactericidal/fungicidal concentration? (MBC/MFC)

A

Minimum concentration of antimicrobial agent at which most organisms are killed

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8
Q

a low MIC (e.g. 0.1mg/L) would indicate what?

A

sensitive organism

NB: sensitivity actually depends on the level available at the site of infection

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9
Q

what is meant by synergism?

A

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

the interaction or cooperation of two or more organizations, substances, or other agents to produce a combined effect greater than the sum of their separate effects.

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10
Q

what is antagonism?

A

One antimicrobial agent diminishes the activity of another, when given at the same time

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11
Q

what is indifference?

A

Activity unaffected by the addition of another antimicrobial agent

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12
Q

what are broad spectrum antimicrobials?

A

kills most types of bacteria/fungi encountered

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13
Q

what are narrow spectrum antimicrobials?

A

kills only a narrow range of organisms

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14
Q

what are the mechanisms of action of antimicrobials?

A

Inhibition of critical process in bacterial/fungal cells – ‘antimicrobial targets’

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15
Q

antimicrobials need to exhibit “selectivity toxicity” - what does this mean?

A

their target is not present or inaccessible in a human host

  • so they cause no harm to humans
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16
Q

list some antimicrobial targets

A
  • Cell wall
  • Protein synthesis
  • DNA synthesis
  • RNA synthesis
  • Plasma membrane
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17
Q

what are ‘antimicrobial targets’?

A

things antimicrobials try and target to inhibit critical processes in bacteria/fungi

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18
Q

what is a bacterial cell wall made up of?

A

peptidoglycan

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19
Q

why is a bacterial cell wall ideal for selective toxicity?

A

no cell wall in animal cells

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20
Q

what are some antibacterial agents that inhibit cell wall synthesis?

A
  • β-lactams

- Glycopeptides

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21
Q

list some β-lactams antibiotics.

A
  • Penicillins
  • Cephalosporins
  • Carbapenems
  • Monobactams
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22
Q

Benzylpenicillin is what type of antibiotic?

A

β-lactams antibiotics

  • penicillin
  • narrow spectrum
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23
Q

amoxicillin is what type of antibiotic?

A

β-lactams antibiotics

  • penicillin
  • narrow spectrum
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24
Q

flucloxacillin is what type of antibiotic?

A

β-lactams antibiotics

  • penicillin
  • narrow spectrum
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25
Q

Cefuroxime is what type of antibiotic?

A

β-lactams antibiotics

  • Cephalosporins
  • broad spectrum
  • arranged into “generations”
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26
Q

ceftazidime is what type of antibiotic?

A

β-lactams antibiotics

  • Cephalosporins
  • broad spectrum
  • arranged into “generations”
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27
Q

which β-lactams antibiotics are broad spectrum?

A

• Cephalosporins
- Cefuroxime, ceftazidime etc.

• Carbapenems
- Meropenem, imipenem

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28
Q

Meropenem is what type of antibiotic?

A

β-lactams antibiotics

  • carbapenems
  • extremely broad spectrum
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29
Q

imipenem is what type of antibiotic?

A

β-lactams antibiotics

  • carbapenems
  • extremely broad spectrum
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30
Q

which β-lactams antibiotics are narrow spectrum?

A

• Penicillins

- Benzylpenicillin, amoxicillin, flucloxacillin

31
Q

which β-lactams antibiotics are gram-negative acting only?

A

• Monobactams

- Aztreonam

32
Q

what type of an antibiotic is Aztreonam?

A

β-lactams antibiotics
• Monobactams
• gram-negative activity only

33
Q

what are β-lactamase enzymes?

A

Enzymes that hydrolyse (inactivate) β-lactams

34
Q

what is a common mechanism or resistance to β-lactam antibiotics?

A

β-lactamase enzymes

35
Q

the β-lactamase enzyme, Staphylococcal β-lactamase, has resistance against what?

A

some penicillins only

36
Q

the β-lactamase enzyme, ‘Extended spectrum β-lactamase’ (ESBL), has resistance against what?

A

penicillins and cephalosporins

37
Q

the β-lactamase enzyme, Carbapenemases (eg NDM1), has resistance against what?

A

carbapenems

38
Q

list some β-lactam/β-lactamase inhibitor combinations (BLBLI).

A

Amocixillin-clavulanate (Augmentin)

Piperacillin-tazobactam (Tazocin)

39
Q

what are some problems with BLBLIs?

A

• Very broad spectrum, so predispose to C. difficile infection

• Names do not end with –illin or start with cef-
- Importance of penicillin allergy may be missed

40
Q

antibacterial glycopeptides inhibit what?

A

bacterial cell wall synthesis

41
Q

give some examples of antibacterial glycopeptides.

A

vancomycin

teicoplanin

42
Q

what type of antibiotic is vancomycin?

A

Glycopeptides

  • inhibit bacterial cell wall synthesis
43
Q

what type of antibiotic is teicoplanin?

A

Glycopeptides

  • inhibit bacterial cell wall synthesi
44
Q

what is a fungal cell wall made of?

A
  • β-1,3-glucan
  • chitin
  • synthesised by β-1,3-glucan synthase
45
Q

what anti fungal agents inhibit cell wall synthesis?

A

Echinocandins

  • Anidulafungin
  • Caspofungin
  • Micafungin
46
Q

how do Echinocandins inhibit cell wall synthesis of fungi?

A
  • Inhibition of β-1,3-glucan synthase

- Construction of severely abnormal cell wall

47
Q

what type of antimicrobial is Anidulafungin?

A
  • anti fungal agent: Echinocandins

- inhibits cell wall synthesis in fungi

48
Q

what type of antimicrobial is

Caspofungin?

A
  • anti fungal agent: Echinocandins

- inhibits cell wall synthesis in fungi

49
Q

what type of antimicrobial is - Micafungin?

A
  • anti fungal agent: Echinocandins

- inhibits cell wall synthesis in fungi

50
Q

what are the 6 types of protein synthesis inhibitors in bacteria?

A
  1. Aminoglycosides
  2. MLS antibiotics
  3. Tetracyclines
  4. Oxazolidinones
  5. Mupirocin
  6. Fusidic acid
51
Q

list some aminoglycosides

A
  • Gentamicin, amikacin

* Bind to 30S ribosomal subunit

52
Q

what type of antibiotic is Gentamicin?

A
  • aminoglycosides

- targets protein synthesis in bacteria

53
Q

what type of antibiotic is amikacin?

A
  • aminoglycosides

- targets protein synthesis in bacteria

54
Q

list some MLS antibiotics

A

• Macrolides, Lincosamides, Streptogramins

  • Erythromycin, clarithromycin (macrolides)
  • Clindamycin (lincosamide)
  • Bind to 50S ribosomal subunit
  • Inhibit protein elongation
55
Q

list some tetracycline antibiotics

A

Tetracycline, doxycycline.

  • Bind to 30S ribosomal subunit. - Inhibit translation by interfering with binding of tRNA to rRNA.
56
Q

name an oxazolidinone antibiotic

A

Linezolid

  • Inhibits initiation of protein synthesis
  • Binds to 50S ribosomal subunit
  • Inhibits assembly of initiation complex
  • May also bind to 70S subunit
57
Q

what type of antibiotic is Erythromycin, and what does it inhibit?

A

MLS antibiotics
- macrolides

inhibits protein elongation (targets protein synthesis)

58
Q

what type of antibiotic is clarithromycin, and what does it inhibit?

A

MLS antibiotics
- macrolides

inhibits protein elongation (targets protein synthesis)

59
Q

what type of antibiotic is Clindamycin, and what does it inhibit?

A

MLS antibiotics - lincosamide

inhibits protein elongation (targets protein synthesis)

60
Q

what type of protein synthesis inhibitors in bacteria Inhibit translation by interfering with binding of tRNA to rRNA?

A

Tetracyclines

Tetracycline, doxycycline.

61
Q

what type of protein synthesis inhibitors in bacteria Inhibit protein elongation?

A

MLS antibiotics

  • Erythromycin, clarithromycin (macrolides)
  • Clindamycin (lincosamide)
62
Q

what type of protein synthesis inhibitors in bacteria Inhibits the initiation of protein synthesis?

A

Oxazolidinones

• Linezolid

63
Q

which antimicrobials inhibit DNA synthesis in bacteria?

A

trimethoprim

sulfonamides

quinolones

fluoroquinolones

64
Q

how do trimethoprim and sulfonamides inhibit DNA synthesis in bacteria?

A

• Both agents inhibit folate synthesis

  • Trimethoprim - dihydrofolate reductase
  • Sulfonamides - dihydropteroate synthetase
65
Q

Trimethoprim is commonly used to treat what?

A

UTI

66
Q

how do quinolones and fluoroquinolones

inhibit DNA synthesis in bacteria?

A

• Inhibit one or more of two related bacterial enzymes

  • DNA gyrase and topoisomerase IV - Involved in remodelling of DNA during DNA replication
67
Q

which antimicrobial agent inhibits DNA gyrase and topoisomerase?

A

quinolones and fluoroquinolones

68
Q

Quinolones are effective against bacteria only; true or false?

A

true

69
Q

what anti fungal agent inhibits DNA synthesis in fungi?

A

5 fluorocytosine (5FC)

• Selectively taken into fungal cells by a fungal enzyme (cytosine permease)

70
Q

what antimicrobial agent prevents the synthesis of mRNA?

A

• Rifampicin

  • RNA polymerase inhibitor
  • Prevents synthesis of mRNA

• Cornerstone of anti-tuberculous chemotherapy

71
Q

which antibacterial agents target the cell membrane in bacteria?

A
  • Colistin (Gram-negatives)1
  • Daptomycin (Gram-positives)2
  • Cyclic lipopeptides
  • Destruction of outer membrane1/cytoplasmic membrane
72
Q

which anti fungal agents target the cell membrane in fungi?

A
  • Azoles (eg clotrimazole, fluconazole)
  • Terbinafine
  • Amphotericin B
73
Q

why would we combine antimicrobial agents?

A

• To provide adequately broad spectrum

• To increase efficacy
- Synergistic combination may improve outcome

• To reduce resistance
- Organism would need to develop resistance to multiple agents simultaneously