12 Anti-microbial therapies Flashcards

1
Q

What is Prontosil?

A

One of the very first examples of an anti-bacterial drug

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2
Q

Prontosil details

A
  • First sulphonamide
  • Bacteriostatic
  • Synthetic
  • Some host toxicity
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3
Q

What does bacteriostatic mean?

A

Does not kill bacteria but stops it from growing

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4
Q

Gram positive bacteria

A

Thick peptidoglycan

Single mebrane

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5
Q

Gram negative bacteria

A

Inner membrane- phospholipids

Outer membrane - mixture of phospholipids and lipopolysaccharides

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6
Q

Why is it easier to develop drugs against gram +ve bacteria?

A

Gram negative –> To get something across outer layer - hydrophilic, to get something across inner layer- hydrophobic
Very difficult to find molecules with both of those properties

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7
Q

How do Beta-lactams work?

A

Interfere with the synthesis of the peptidoglycan component of the bacterial cell wall
- Bind to penicillin binding proteins, binding to active sites and inactivating them

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8
Q

Examples of Beta-lactams

A

Penicillin

Methicillin

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9
Q

What is an antibiotic?

A

An antimicrobial agent produced by a microorganism that kills or inhibits other microirganisms

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10
Q

What does antimicrobial mean?

A

Chemical that selectively kills or inhibits microbes

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11
Q

What does bactericidal mean?

A

Kills bacteria

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12
Q

What does antiseptic mean?

A

Chemical that kills or inhibits microbes that is usually used topically to prevent infection

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13
Q

What is the minimal inhibitory concentration (MIC)?

A

The lowest concentration of antibiotics required to inhibit growth

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14
Q

Three stages of resistance

A
  • Sensitive (killed, inhibited by low concs)
  • Intermediate
  • Resistant
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15
Q

What is a high concentration of antibiotics?

A

Any concentration that is above what can be achieved clinically (breakpoint)

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16
Q

Antibiotic resistance comes about by

A

Natural selection (certain strains resistant before use due to mutations)

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17
Q

What happens when a selection pressure such as an antibiotic is applied?

A

Susceptible bugs are killed off, resistant bugs are left - high prevalence of AB resistant strains

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18
Q

Vancomycin

A

Resistance reported much later

Not used very much, very toxic

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19
Q

Diagnostics and bacteriology can take

A

24-48 hrs to get susceptibility

20
Q

Examples of aminoglycosides

A

Gentamicin

Streptomycin

21
Q

How do aminoglycosides work?

A

Bactericidal

  • Inhibit protein synthesis (30S ribosomal subunit) and RNA proofreading causing damage to the cell mebrane
  • Very toxic
22
Q

How does rifampicin work?

A

Bacericidal

  • Targets RpoB subunit of RNA polymerase
  • Makes secretions go orange/red affecting compliance
23
Q

How does vancomycin work?

A

Bactericidal

  • Targets Lipid II component of cell wall biosynthesis and cross linking
  • Toxic (limited use)
24
Q

How does linezolid work?

A

Bacteriostatic

  • Inhibits initiation of protein synthesis by binding to 50S rRNA subunit
  • Gram +ve only
25
How does daptomycin work?
Bactericidal - Targets bacterial cell mebrane - Gram +ve - Toxic
26
4 mechanisms of antibiotic resistance
- Altered target site - Inactivation of antibiotic - Altered metabolism - Decreased drug accumulation
27
How does an altered target site work?
- Gene encoding target modifying enzyme | - e.g. MRSA encodes alternative PBP with ow affinity for beta-lactams
28
How does inactivation of antibiotic occur?
- Enzymatic degradation/alteration - Beta-lactamase - e.g. ESBL, NDM-1
29
How does altered metabolism work?
- Increased production of enzyme substrate (competitive inhibition) - Bacteria can switch to other metabolic pathways
30
How does decreased drug accumulation work?
Reduced penetration of antiobiotic into bacterial cell or increased efflux of AB out of the cell (pumping out)
31
How do macrolides work?
Target 50S ribosomal subunit preventing amino-acyl transfer (+ve + -ve)
32
Examples of macrolides
Erythromycin | Azithromycin
33
How do quinolones work?
Bactericidal | Target DNA gyrase in -ve and topoisomera IV in +ve
34
How are plasmids sources of resistant genes?
Can be swapped between bacteria, carry multiple AB res genes
35
How are transposons a source of resistance?
Integrate into chromosomal DNA, transfer genes from plasmid to chromosome
36
How is naked DNA a source of resistance?
DNA from dead bacteria is released into the environment
37
What is transformation?
Uptake of extracellular DNA
38
What is transduction?
Phage-mediated DNA transfer
39
What is conjugation?
Pilus-mediated DNA transfer
40
Measurements made in vitro
May not fully reflect the situation in vivo
41
Why is HAI a big problem?
Hospitals provide strong selective pressure for AB resistance Large numbers of people re receiving high doses
42
Examples of HAIs
- MRSA - Clostridium difficile - E. coli - Acineterbacter baumannii - VISA (vancomycin insensitive S aureus)
43
Risk factors for HAI
- Immunosupression - Crowded wards - Presence of pathogens - Broken skin (wounds) - Staff --> vectors
44
How to slow down resistance
- Reduce use of broad-spectrum - Combination therapy - Tighter controls, restrictions
45
What may be used in the future?
- New antibiotics/vaccines - Better screening - Novel approaches (phae lysins, photo active compounds)