Public: Beta Lactam antibiotics and Vancomycin

Question 1

Give the bacterial cell wall function(s)

Answer 1

• Protects the cytoplasmic membrane from rupture, as the cell membrane is fragile and osmotic pressure inside of the cell is high.
• Maintains the shape of the cell

Question 2

Describe the cell walls of norcardioform bacteria

e.g. M.tuberculosis

Answer 2

Gram positive but difficult to stain
peptidoglycan is covalently linked to the polysaccharide arabinogalactan
Lipids are esterified to arabinogalactan and make up 60% of the dry cell weight
Lipids confer resistance to staining, antibiotics and biocides

Question 3

What is the major structural component of gram positive and gram negative cell walls?

Answer 3

Peptidoglycan

Question 4

What does peptidoglycan consist of?

Answer 4

A repeating disaccharide unit of 2 different N-acetylated aminosugars
Short peptide chains are attached to alternate aminosugars and these crosslink to one another via peptide bonds.
Some bacteria have many sheets of peptidoglycan and these are joined by the same type of crosslink

Question 5

Are the crosslinks between the polysaccharide chains are species dependent?

Answer 5

Yes

Question 6

How are crosslinks in bacterial cell walls formed?

Answer 6

Crosslinks are formed by a transpeptidation reaction, catalysed by a membrae-bound transpeptidase.

Question 7

Name one of a number of enzymes in the cell membrane that acts on cell wall synthesis.

Answer 7

carboxypeptidase

Question 8

Name 3 types of beta lactam antibiotics

Answer 8

Penicillins
Cephalosporins
Carbapenems

Question 9

Name 3 amino acids that are (somewhat) in penicillin

Answer 9

Valine

Cysteine

Phenylalanine

Question 10

What factors control the activity and usefulness of beta lactam antibiotics?

Answer 10

• Ability to penetrate the cell wall
• Resistance to -lactamases
• Affinity of various Penicillin Binding Proteins
• Resistance to stomach acid
• Formulation, pharmacokinetics, toxicology etc.

Question 11

Which penicillin was the original? What are the downfalls of using this?

Answer 11

Penicillin G

Acid labile therefore injection, sensitive to ß-lactamase degradation

Question 12

Name 4 semi-synthetic penicillins

Answer 12

Ampicillin
Amoxicillin
Methicillin
Flucloxacillin

Question 13

Ampicillin is better than penicillin in what way?

Any downfalls to it?

Answer 13

Acid-stable therefore oral route of administration

sensitive to beta-lactamase degradation

Question 14

Amoxicillin is better than penicillin in what way?

Answer 14

resistant to class 1 beta-lactamase enzymes

Question 15

Methicillin and Flucloaccilin are resistant to…

Answer 15

all beta-lactamases

Question 16

Talk about cephlasporins structure and also the various different generations of them

Answer 16

Cephlasporin nucleus is biosynthesised in a similar way to the penicillin nucleus
Generation 1 - seldom used any more
Generation 2 - Have gram negative activity and are administered orally
Generation 3 - good gram negative activity and are useful against very serious illness. They are injected.

Question 17

Give an example of a 2nd generation cephlasporin and what it is used to treat

Answer 17

Cefaclor

Gram negative activity and activity against Haemophilus

Question 18

Give an example of a 3rd generation cephlasporin and what it is used to treat

Answer 18

Ceftriaxone

Given by intramuscular injection for serious infections, often in combination with a macrolide and an aminoglycoside

Question 19

Describe advantages of carbapenems

Answer 19

Very broad spectrum

Resistant to most beta-lactamases

Question 20

Monobactams?

Answer 20

Only one so far - Aztreonam

active against gram negatives only

Question 21

Give an example of a carbapenem and describe its use

Answer 21

Imipenem

Rapidly deactivated by the kidneys unless administered with a certain inhibitor, Cilastatin

Question 22

Describe the structure of Vancomycin

Answer 22

It’s a non-ribosomal polypeptide
Made from many unusual amino acids
Glycosolated
Product of the soil microorganism Amycolatopsis orientalis

Question 23

How does Vancomycin work?

Answer 23

Pushes apart crosslinks in the cell wall i.e. prevents cross link formation

Question 24

Uses of vancomycin

Answer 24

Serious gram positive infections only (as it doesn’t cross the gram negative cell wall)

Question 25

Why is vancomycin normally injected?

Answer 25

Because the digestive system is designed to hydrolyse peptide bonds, of which vancomycin has many

Question 26

What does oral vancomycin treat?

Answer 26

Clostridium diffcile infections

Question 27

Describe the disagreement clinicians have regarding vancomycin use

Answer 27

Some commentators do not recommend vancomycin for treatment of MRSA, preferring nafcillin. However, injected rifampicin – vancomycin combination is preferred by many trusts.

Question 28

3 reasons why vancomycin side effects may have been exaggerated

Answer 28

1) early preparations of vancomycin were very impure
2) People who reported nephrotoxicity were generally taking other nephrotoxins
3) Ototoxicity is rare

Question 29

Name an alternative to vancomycin that is used

Answer 29

Teicoplanin
(another glycopeptide)
Mode of action believed to be very similar

Question 30

When was vancomycin resistance first reported in the UK?

Answer 30

1999