Lecture 12 - Intro to antibiotics Flashcards

1
Q

What is an antibiotic?

A

A chemical produced by a microorganism that kills or inhibits other microorganisms

(Synthetic or semisynthetic antimicrobials are not strictly antibiotics by definition)

It is now more commonly referring to agents that are active against bacteria and can be natural, synthetic, or semisynthetic

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2
Q

Where do antibiotics come from?

A

Antibiotics can be from other microorganisms, semi-synthetic, or synthetic

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3
Q

Give some examples of semi-synthetic antibiotics:

A

Meropenem

Amikacin

Azithromycin

Rifampicin

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4
Q

What are some examples of synthetic antibiotics?

A

Sulfa drugs (eg sulfamethoxazole)

Quinolones (eg. ciprofloxacin)

Oxazolidinones (eg. Linezolid)

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5
Q

What are the classes of antibiotics?

A

Beta-lactams

Beta-lactam/Beta-lactamase inhibitor combinations

Glycopeptides

Quinolones

Macrolides

Tetracyclines

Lincosamides

Aminoglycosides

Lipopeptides

Oxazolidinones

Streptogramines

Sulfonamides

Miscellanious

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6
Q

Why are carbapenums used as a last resort?

A

They are very broad spectrum

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7
Q

How is the cell wall assembled in bacteria?

A

Cell wall precursors are produced in the cytoplasm and then moved through the cell membrane.

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8
Q

How is the cell wall of bacteria produced?

A

Precursors are produced containing glycans and a small amino acid chain with 2 terminal D-alanines and a pentapeptide bridge which connects with the other precursors.

Carboxypeptidase cleaves 1 D-alanine and joins precursor onto the growing chain.

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9
Q

What enzyme joins peptidoglycans precursors to each other outside the cell membrane?

A

Transpeptidase

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10
Q

What other enzymes are involved in elongation of peptidoglycan chain?

A

Transglycosylase

Carboxypeptidase

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11
Q

How do beta lactam antibiotics work?

A

They inhibit binding of precursor molecules onto the elongating cell wall.

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12
Q

How do glycopeptides work?

A

They also inhibit formation of cell wall by binding the D-ala D-ala end of the precursor side chain resulting in an inability of the precursor to bind to the transpeptidases

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13
Q

Which 2 antibiotics work on the cell wall?

A

Glycopeptides

Beta lactam antibiotics

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14
Q

How do rifamycins work?

A

They inhibit the enzyme that produces mRNA (RNA polymerase) from the DNA template

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15
Q

How do Macrolides, Clindamycin, streptogramins, and oxazolidinones work?

A

They inhibit protein production by binding to the 50S ribosome and inhibiting protein elongation.

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16
Q

Which antibiotics inhibit protein production by binding to the 50S ribosome/?

A

Macrolides

Clindamycin

Streptogramins

Oxazolidinones

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17
Q

How do aminoglycosides work?

A

Bind to 30S and cause misreading of the code

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18
Q

Which antibiotics cause misreading of the code by binding to 30S ribisome?

A

Aminoglycosides

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19
Q

How do tetracyclines and tigecycline work?

A

They block binding of tRNA to 30S ribosome

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20
Q

Which antibiotics prevent translation by blocking tRNA binding to ribosome?

A

Tetracyclines

Tigecycline

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21
Q

What antibiotics inhibit folate synthesis?

A

Para aminobenzoid acid (PABA)

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22
Q

What is folate used for in bacteria?

A

They are important for the production of DNA and RNA.

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23
Q

What does PABA act on?

A

Folate synthesis

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24
Q

What are the enzymes involved in the synthesis of folate?

A

Dihydropteroate

Dihydrofolate reductase

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25
Q

What do sulfonamides act on?

A

Dihydropteroate

26
Q

What does trimethoprim work on?

A

Dihydrofolate reductase

27
Q

Is trimethoprim used alone?

A

Yes, but only for UTIs.

It is most often combined with other antibiotics

28
Q

Which bacterial enzymes are involved in DNA replication?

A

DNA gyrase and DNA topoisomerase

29
Q

Which antibiotics act on the bacterial enzymes involved in DNA replication?

A

Quinolones, they also interfere with mRNA production

30
Q

What does daptomycin do?

A

It has a lipophilic tail which allows it to insert itself into cytoplasmic membrane. It transports potassium out of the cell depolarizing the cell membrane and thus killing it.

31
Q

What is augmentin?

A

Amoxicillin combined with a beta lactamase inhibitor

32
Q

What consideration should be made when choosing antibiotics?

A

That it is as specific to the pathogenic bacteria as possible

33
Q

What is targeted therapy?

A

Specimens are collected and investigated and causative organism is isolated in the lab and tested against a range of antibiotics and based on those results the appropriate antibiotic is prescribed.

34
Q

What is targeted therapy?

A

Specimens are collected and investigated and causative organism is isolated in the lab and tested against a range of antibiotics and based on those results the appropriate antibiotic is prescribed.

35
Q

When is empirical therapy used?

A

When specimens are not available for lab investigation or while waiting for results of lab investigations

36
Q

What is the issue with using empirical therapy?

A

It requires a more broad spectrum than directed therapy.

37
Q

Why is narrow spectrum preferable to broad spectrum?

A

Broad spectrum therapy:

Encourages antibiotic resistance

Kills more normal flora

Poses greater risk of adverse effects

38
Q

What is the minimum inhibitory concentration?

A

The minimum concentration of antibiotic that inhibits visible growth of bacteria in an in vitro system

39
Q

How is the minimum inhibitory concentration decided?

A

Different amounts of the antibiotic are added to broth colture media. (starting from 0 and then increasing by double after the next test tube).

Standardised bacterial inoculum is added to each of the test tubes and this is incubated overnight.

40
Q

How is the MIC normally tested?

A

Antibiotic filter paper discs added to a lawn inoculum in nutritious agar.

Antibiotic diffuses out in a gradient and bacteria receive less antibiotic further away from inoculum.

41
Q

What does MIC tell us about the antibiotic we want to use?

A

It tells us more information about the regimen we should use and the duration it should be used.

42
Q

What does MIC tell us about the bacteria?

A

Whether it is sensitive or resistant

43
Q

What causes inherent resistant to antibiotics?

A

The natural competition between bacteria.

44
Q

How do bacteria gain antibiotic resistance?

A

They may gain it through horizontal gene transfer.

Some can arise as a result of excess antibiotic use allowing only resistant individuals to survive

45
Q

How do bacteria resist antibiotics?

A

Active removal of antibiotic from cell. (pumping antibiotic out faster than it gets in)

Inhibition of antibiotic entry to target site (changing porin site)

Production of enzymes which modify or destroy antibiotics

Alteration of antibiotic’s target so it can no longer bind

46
Q

Where are antibiotic resistance genes typically found?

A

On plasmids

47
Q

Where are antibiotic efflux pumps and porin channels located?

A

Gram negative outer membrane

48
Q

How does pseudomonas aeruginosa confer resistance to imipenem?

A

Mutation in porD creates an aberrant oprD porin protein causing imipenem to no longer be able to enter the cell

49
Q

What are the methods by which bacteria produce antibiotic modifying/destroying enzymes?

A

Modify: Aminoglycoside modifying enzymes, acetyltransfer

50
Q

How can bacterial enzymes modify aminoglycosides?

A

They produce specialized aminoglycoside modifying enzymes

Acetyltransferases

Adenyltransferases

Phosphotransferases

51
Q

How can bacterial enzymes destroy antibiotics?

A

Beta - lactamases (break the beta lactam ring)

52
Q

How many beta lactamases have been identified?

A

more than 1000

53
Q

What are some examples of beta-lactamases?

A

Penicillinases

Cephalosporinases

Carbapenemases

54
Q

What are the 2 ways in which bacteria can produce enzymes to avoid antibiotic actions?

A

They can produce antibiotic modifying enzymes

They can produce antibiotic destroying enzymes

55
Q

What percentage of staph aureus are resistant to penicillin?

A

80% or more

56
Q

What did scientists do to make beta lactam antibiotics more effective against beta lactamases?

A

They produced new antibiotics that can resist the bacterial beta-lactamase.

57
Q

What are the new penicillins produced to combat beta lactamases?

A

Methicillin

Flucloxacillin

58
Q

What are the new cephalosporins produced to combat beta lactamases?

A

Cephalexin

and many others

59
Q

What is the response of staph aureus to the new beta lactamases?

A

New strains of S.aureus are resistant to all beta lactams by a different mechanism.

PBP2 on has been replaced by mecA gene which encodes for PBP2a which is a lower affinity receptor for the antibiotic which can still elongate the cell wall.

60
Q

What is another name for the binding site of beta lactam antibiotics?

A

PBP2

61
Q

How are antibiotics administered?

A

Dose, frequency, and route of administration will vary.

When antibiotics are chosen for severe infections the choice is parenteral and then when things calm down oral is used to continue.