Lecture 12 - Intro to antibiotics

Question 1

What is an antibiotic?

Answer 1

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

Question 2

Where do antibiotics come from?

Answer 2

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

Question 3

Give some examples of semi-synthetic antibiotics:

Answer 3

Meropenem

Amikacin

Azithromycin

Rifampicin

Question 4

What are some examples of synthetic antibiotics?

Answer 4

Sulfa drugs (eg sulfamethoxazole)

Quinolones (eg. ciprofloxacin)

Oxazolidinones (eg. Linezolid)

Question 5

What are the classes of antibiotics?

Answer 5

Beta-lactams

Beta-lactam/Beta-lactamase inhibitor combinations

Glycopeptides

Quinolones

Macrolides

Tetracyclines

Lincosamides

Aminoglycosides

Lipopeptides

Oxazolidinones

Streptogramines

Sulfonamides

Miscellanious

Question 6

Why are carbapenums used as a last resort?

Answer 6

They are very broad spectrum

Question 7

How is the cell wall assembled in bacteria?

Answer 7

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

Question 8

How is the cell wall of bacteria produced?

Answer 8

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.

Question 9

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

Answer 9

Transpeptidase

Question 10

What other enzymes are involved in elongation of peptidoglycan chain?

Answer 10

Transglycosylase

Carboxypeptidase

Question 11

How do beta lactam antibiotics work?

Answer 11

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

Question 12

How do glycopeptides work?

Answer 12

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

Question 13

Which 2 antibiotics work on the cell wall?

Answer 13

Glycopeptides

Beta lactam antibiotics

Question 14

How do rifamycins work?

Answer 14

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

Question 15

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

Answer 15

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

Question 16

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

Answer 16

Macrolides

Clindamycin

Streptogramins

Oxazolidinones

Question 17

How do aminoglycosides work?

Answer 17

Bind to 30S and cause misreading of the code

Question 18

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

Answer 18

Aminoglycosides

Question 19

How do tetracyclines and tigecycline work?

Answer 19

They block binding of tRNA to 30S ribosome

Question 20

Which antibiotics prevent translation by blocking tRNA binding to ribosome?

Answer 20

Tetracyclines

Tigecycline

Question 21

What antibiotics inhibit folate synthesis?

Answer 21

Para aminobenzoid acid (PABA)

Question 22

What is folate used for in bacteria?

Answer 22

They are important for the production of DNA and RNA.

Question 23

What does PABA act on?

Answer 23

Folate synthesis

Question 24

What are the enzymes involved in the synthesis of folate?

Answer 24

Dihydropteroate

Dihydrofolate reductase

Question 25

What do sulfonamides act on?

Answer 25

Dihydropteroate

Question 26

What does trimethoprim work on?

Answer 26

Dihydrofolate reductase

Question 27

Is trimethoprim used alone?

Answer 27

Yes, but only for UTIs. It is most often combined with other antibiotics

Question 28

Which bacterial enzymes are involved in DNA replication?

Answer 28

DNA gyrase and DNA topoisomerase

Question 29

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

Answer 29

Quinolones, they also interfere with mRNA production

Question 30

What does daptomycin do?

Answer 30

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.

Question 31

What is augmentin?

Answer 31

Amoxicillin combined with a beta lactamase inhibitor

Question 32

What consideration should be made when choosing antibiotics?

Answer 32

That it is as specific to the pathogenic bacteria as possible

Question 33

What is targeted therapy?

Answer 33

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.

Question 34

What is targeted therapy?

Answer 34

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.

Question 35

When is empirical therapy used?

Answer 35

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

Question 36

What is the issue with using empirical therapy?

Answer 36

It requires a more broad spectrum than directed therapy.

Question 37

Why is narrow spectrum preferable to broad spectrum?

Answer 37

Broad spectrum therapy: Encourages antibiotic resistance Kills more normal flora Poses greater risk of adverse effects

Question 38

What is the minimum inhibitory concentration?

Answer 38

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

Question 39

How is the minimum inhibitory concentration decided?

Answer 39

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.

Question 40

How is the MIC normally tested?

Answer 40

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.

Question 41

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

Answer 41

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

Question 42

What does MIC tell us about the bacteria?

Answer 42

Whether it is sensitive or resistant

Question 43

What causes inherent resistant to antibiotics?

Answer 43

The natural competition between bacteria.

Question 44

How do bacteria gain antibiotic resistance?

Answer 44

They may gain it through horizontal gene transfer. Some can arise as a result of excess antibiotic use allowing only resistant individuals to survive

Question 45

How do bacteria resist antibiotics?

Answer 45

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

Question 46

Where are antibiotic resistance genes typically found?

Answer 46

On plasmids

Question 47

Where are antibiotic efflux pumps and porin channels located?

Answer 47

Gram negative outer membrane

Question 48

How does pseudomonas aeruginosa confer resistance to imipenem?

Answer 48

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

Question 49

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

Answer 49

Modify: Aminoglycoside modifying enzymes, acetyltransfer

Question 50

How can bacterial enzymes modify aminoglycosides?

Answer 50

They produce specialized aminoglycoside modifying enzymes Acetyltransferases Adenyltransferases Phosphotransferases

Question 51

How can bacterial enzymes destroy antibiotics?

Answer 51

Beta - lactamases (break the beta lactam ring)

Question 52

How many beta lactamases have been identified?

Answer 52

more than 1000

Question 53

What are some examples of beta-lactamases?

Answer 53

Penicillinases Cephalosporinases Carbapenemases

Question 54

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

Answer 54

They can produce antibiotic modifying enzymes They can produce antibiotic destroying enzymes

Question 55

What percentage of staph aureus are resistant to penicillin?

Answer 55

80% or more

Question 56

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

Answer 56

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

Question 57

What are the new penicillins produced to combat beta lactamases?

Answer 57

Methicillin Flucloxacillin

Question 58

What are the new cephalosporins produced to combat beta lactamases?

Answer 58

Cephalexin and many others

Question 59

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

Answer 59

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.

Question 60

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

Answer 60

PBP2

Question 61

How are antibiotics administered?

Answer 61

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.