1. Antimicrobial agents & antibiotic resistance Flashcards

1
Q

What is the difference between antibiotics and antimicrobial agents?

A

ANTIBIOTICS - natural chemical products of microbes that inhibit/kill other organisms
ANTIMICROBIAL AGENTS - synthetic/semi-synthetic compounds & antibiotics

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2
Q

What is the difference between bacteriostatic and bactericidal?

A

BACTERIOSTATIC - Inhibits bacterial growth (protein synthesis)
BACTERICIDAL - kills bacteria (cell wall agents)

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3
Q

What is the MIC, and what does it mean?

A

MINIMUM INHIBITORY CONCENTRATION

  • minimum concentration at which visible growth is inhibited
  • NB. smaller MIC = more active antibiotic
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4
Q

What is synergism (antimicrobial interactions)?

A

The interaction of 2 antimicrobials to produce a combined effect greater than the sum of their activity given separately.

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5
Q

Give an example of synergism that is used to treat endocarditis.

A

B-lactam & aminoglycoside

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6
Q

What is antagonism?

A

One agent diminishes the activity of another.

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7
Q

What are antibiotic targets in cells? (4)

A

Cell wall
Protein synthesis
DNA & RNA synthesis
Plasma membrane

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8
Q

What is the main component of bacterial cell walls?

A

Peptidoglycan

- polymer of glucose derivatives (NAM &NAG)

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9
Q

Why is the bacterial cell wall an ideal target for antibacterial agents?

A

Selective toxicity - no cell wall in animal cells

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10
Q

Give 2 examples of synthesis inhibitors of bacterial cell walls.

A

B-lactams (ring structure)

Glycopeptides

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11
Q

How does b-lactam act on bacterial cell walls?

A

Forms structural analogue of D-alanyl-D-alanine & interferes with function of penicillin binding protein.

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12
Q

Give examples of B-lactams. (4)

A

Penicillins
Cephalosporins
Carbapenems
Monobactams (gram -ve only)

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13
Q

How do glycopeptides act on bacterial cell walls?

A

They bind to terminal D-alanyl-D-alanine on NAM pentapeptides&raquo_space; inhibit cross-linking.

  • unable to penetrate gram -ve porins
  • eg. Vancomycin
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14
Q

What happens during bacterial protein synthesis?

A

Translation of RNA&raquo_space; protein.

- 50S & 30S combine&raquo_space; 70S (initiation complex)

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15
Q

What are the 5 main types of protein synthesis inhibitors?

A
Amino glycosides
Macrolides, lincosamides, streptogramins (MLS)
Tetracyclines
Oxazolidinones
Other (fusidic acid, mupirocin)
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16
Q

How do aminoglycosides inhibit protein synthesis?

-Give an example.

A

Bind to 30S subunit

-gentamycin

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17
Q

How do tetracyclines inhibit protein synthesis?

-Give an example.

A

Bind to 30S&raquo_space; inhibit RNA translation (tRNA&raquo_space; rRNA)

-DOxytetracycline

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18
Q

How do oxazolidionones inhibit protein synthesis?

-Give an example.

A

Bind to 50S (&70S)&raquo_space; inhibit initiation of protein sysnthesis.
-Linezolid

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19
Q

Name 4 types of DNA synthesis inhibitor.

A

Trimethoprim & sulfonamides (combine&raquo_space; CO-TRIMOXAZOLE), quinolones & fluoroquinolones

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20
Q

How do trimethoprim & sulfonmides inhibit DNA synthesis?

A

Inhibit folate acid synthesis

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21
Q

What is a side effect of co-trimoxazole?

A

Stevens-Johnson syndrome

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22
Q

How do quinolones & fluoroquinolones inhibit DNA synthesis?

A

Inhibit DNA gyrase & topoisomerase IV (DNA remodelling)

- eg. nalidixic acid, ciprofloxacin

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23
Q

Name an RNA synthesis inhibitor.

A

Rifampicin

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24
Q

How does rifampicin inhibit RNA synthesis?

A

RNA polymerase inhibitor&raquo_space; prevents mRNA synthesis

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25
Q

What is daptomycin and how does it act on bacteria?

A

Plasma membrane agent

-inserts lipophilic tail into cell membrane of gram +ve bacteria&raquo_space; depolarisation

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26
Q

What are the side effects of aminoglycosides?

A

Renal impairment & ototoxicity (ear)

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27
Q

What are the side effects of linezolid?

A

Bone marrow depression

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28
Q

What are the side effects of B-lactams?

A

Allergic reactions (rash, anaphylaxis - rare)

29
Q

What is used instead of B-lactams if a patient is allergic?

A

Non-specific penicillin allergy: CEPHALOSPORINS & CARBAPENEMS
Any penicillin allergy: AZTREONAM

30
Q

What is the most common cause of antibiotic-associated diarrhoea?

A

C. difficile

-Hypervirulent strain 027 = most severe

31
Q

How does C. difficile cause diarrhoea, and what are common precipitating antibiotics associated with it?

A

Produces toxins A&B due to removal of normal colonisation resistance
- cephalosporins & ciprofloxacin

32
Q

What is the strategy for antibiotic use?

A
  1. EMPIRIC THERAPY (know organ system, based on predicted susceptibility of likely pathogen)
  2. TARGETED THERAPY (know infecting organism, based on predicted susceptibility)
  3. SUSCEPTIBILITY-GUIDED THERAPY (based on antimicrobial susceptibility results)
33
Q

What are the key antibiotic/bacteria combination for:

  • flucloxacillin?
  • benzylpenicillin?
  • cephalosporins?
  • metronidazole?
  • vancomycins?
  • meropenem?
A
  • flucloxacillin & s. aureus
  • benzylpenicillin & s. pyogenes
  • cephalosporins & gram -ve bacteria
  • metronidazole & anaerobes
  • vancomycins & gram +ve bacteria
  • meropenem & most bacteria
34
Q

What is the main bacteria flucloxacillin is used against?

A

S. aureus

35
Q

What is the main bacteria benzylpenicillin is used against?

A

S. pyogenes

36
Q

What type of bacteria is cephlosporins used against?

A

Gram -ve bacteria

37
Q

What type of bacteria is metronidazole used against?

A

Anaerobes

38
Q

What type of bacteria is vancomycins used against?

A

Gram +ve bacteria

39
Q

What type of bacteria is meropenem used against?

A

Most bacteria

40
Q

Which antibacterial agents have good availability in CSF?

A

B-lactams

41
Q

Which antibacterial agents have poor availability in CSF?

A

Vancomycin & aminoglycosides

42
Q

Which antibacterial agents have good availability in urine?

A

Trimethoprim & B-lactams

43
Q

Which antibacterial agents have poor availability in urine?

A

MLS

44
Q

What are the reasons for using combination therapies? (3)

A

Increase efficacy
Provide broad spectrum (eg. sepsis)
Decrease resistance

45
Q

Give an example of 2 antimicrobial agent that have an increased efficacy when used together.

A

B-lactam/aminoglycosides

|&raquo_space; endocarditis

46
Q

What is meant by the ‘antibiotic era’?

A

Widespread availability of antibiotics (1940s)

47
Q

What is meant by the ‘post-antibiotic era’?

A

Gradual resistance&raquo_space; decreased availability

48
Q

Give some examples of problematic bacteria.

A
MRSA
VRE
ESBL (B-lactamase)
CBE (carbapenamase)
Multi-drug resistant TB
49
Q

What problems does antibiotic resistance cause for empiric treatment?

A

Risk of under-treatment

Risk of using excessively broad spectrum

50
Q

What problems does antibiotic resistance cause for targeted therapy?

A

Requires use of alternatives

  • EXPENSIVE (eg. linezolid for MRSA)
  • “LAST-LINE” (eg. meropenem for multi-resistant enterobacteriaceae)
  • TOXIC (eg. colistin for NDM-1 producers)
51
Q

What is the process of sensitivity testing?

A
  • culture microorganism in presence of anti-microbial agent
  • organism grow = RESISTANT, doesn’t grow = SENSITIVE
  • determine whether MIC is above predetermined ‘breakpoint’
52
Q

What are the reasons for sensitivity testing? (4)

A
  • Transition from empiric&raquo_space; targeted treatment
  • Explains treatment failures
  • Provides alternative antibiotics (eg. adverse effects)
  • Transition from IV&raquo_space; oral antibiotics
53
Q

What type of media gives a more accurate MIC during sensitivity testing?

A

A liquid media

-lower MIC = more sensitive organism

54
Q

What are the limitations of sensitivity testing?

A
  • infection may be caused by another organism
  • correlation between antimicrobial sensitivity & clinical response is not absolute
  • some organisms appear to respond but are clinically resistant
55
Q

What are the 6 mechanisms of antibiotic resistance?

A
  1. No target&raquo_space; no effect
  2. Decrease permeability (drug can’t get it)
  3. Altered target
  4. Over-expression of target (»effect diluted)
  5. Enzymatic degradation (drug destroyed)
  6. Efflux pump (»drug expelled)
56
Q

Give an example when no target leads to antibiotic resistance.

A

Using antibiotics&raquo_space; fungi/virus

57
Q

Give 2 examples when decreased permeability leads to antibiotic resistance.

A
  • VANCOMYCIN: cannot permeate gram -ve bacteria

- GENTAMICIN: cannot permeate anaerobes (uptake requires o2 dependent AT)

58
Q

Give an example when an altered target leads to antibiotic resistance.

A

Flucloxacillin: MRSA

-Altered penicillin-binding protein does not bind β-lactams

59
Q

Give an example when enzymatic degradation leads to antibiotic resistance.

A

Penicillins & cephalosporins degrade β-lactamases

60
Q

Give an example where efflux pumps lead to antibiotic resistance.

A

Many antibiotics, particularly in Gram -ve bacteria

-Eg. Candida spp.

61
Q

How do bacteria become resistant to antibiotics?

A
  • single gene resistance
  • resistance encoded in plasmids
  • horizontal transfer
  • vertical transfer
62
Q

How do single genes lead to antibiotic resistance?

A
  • Antibiotic-modifying enzymes

- Altered antibiotic targets

63
Q

Give 2 examples of antibiotic-modifying enzymes

A
  • B-lactamases (penicillins, cephalosporins)

- Aminoglycoside-modifying enzymes (gentamycin)

64
Q

Give an examples of an altered antibiotic target.

A

-Penicillin-binding protein 2 (MRSA)

65
Q

How are plasmids normally transmitted within/between species?

A

Conjugation

66
Q

What molecules enable horizontal transfer of resistance? (2)

A

Integrons

Transposons

67
Q

What is horizontal transfer?

A

Transfer of DNA between different genomes

-from plasmid&raquo_space; plasmid/chromosome

68
Q

What is vertical transfer?

A

Transfer of genes from parent to offspring

-asexual/sexual

69
Q

What are the consequences of antibiotic exposure? (2)

A
  • Sensitive strains exposed to sub-lethal concentrations
  • Resistance enhances the chance of survival&raquo_space; out-competes sensitive strains (subsequent infection more likely to be sure to resistant strain)