Public: Beta Lactam antibiotics and Vancomycin Flashcards
Give the bacterial cell wall function(s)
- 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
Describe the cell walls of norcardioform bacteria
e.g. M.tuberculosis
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
What is the major structural component of gram positive and gram negative cell walls?
Peptidoglycan
What does peptidoglycan consist of?
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
Are the crosslinks between the polysaccharide chains are species dependent?
Yes
How are crosslinks in bacterial cell walls formed?
Crosslinks are formed by a transpeptidation reaction, catalysed by a membrae-bound transpeptidase.
Name one of a number of enzymes in the cell membrane that acts on cell wall synthesis.
carboxypeptidase
Name 3 types of beta lactam antibiotics
Penicillins
Cephalosporins
Carbapenems
Name 3 amino acids that are (somewhat) in penicillin
Valine
Cysteine
Phenylalanine
What factors control the activity and usefulness of beta lactam antibiotics?
- Ability to penetrate the cell wall
- Resistance to -lactamases
- Affinity of various Penicillin Binding Proteins
- Resistance to stomach acid
- Formulation, pharmacokinetics, toxicology etc.
Which penicillin was the original? What are the downfalls of using this?
Penicillin G
Acid labile therefore injection, sensitive to ß-lactamase degradation
Name 4 semi-synthetic penicillins
Ampicillin
Amoxicillin
Methicillin
Flucloxacillin
Ampicillin is better than penicillin in what way?
Any downfalls to it?
Acid-stable therefore oral route of administration
sensitive to beta-lactamase degradation
Amoxicillin is better than penicillin in what way?
resistant to class 1 beta-lactamase enzymes
Methicillin and Flucloaccilin are resistant to…
all beta-lactamases
Talk about cephlasporins structure and also the various different generations of them
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.
Give an example of a 2nd generation cephlasporin and what it is used to treat
Cefaclor
Gram negative activity and activity against Haemophilus
Give an example of a 3rd generation cephlasporin and what it is used to treat
Ceftriaxone
Given by intramuscular injection for serious infections, often in combination with a macrolide and an aminoglycoside
Describe advantages of carbapenems
Very broad spectrum
Resistant to most beta-lactamases
Monobactams?
Only one so far - Aztreonam
active against gram negatives only
Give an example of a carbapenem and describe its use
Imipenem
Rapidly deactivated by the kidneys unless administered with a certain inhibitor, Cilastatin
Describe the structure of Vancomycin
It’s a non-ribosomal polypeptide
Made from many unusual amino acids
Glycosolated
Product of the soil microorganism Amycolatopsis orientalis
How does Vancomycin work?
Pushes apart crosslinks in the cell wall i.e. prevents cross link formation
Uses of vancomycin
Serious gram positive infections only (as it doesn’t cross the gram negative cell wall)
Why is vancomycin normally injected?
Because the digestive system is designed to hydrolyse peptide bonds, of which vancomycin has many
What does oral vancomycin treat?
Clostridium diffcile infections
Describe the disagreement clinicians have regarding vancomycin use
Some commentators do not recommend vancomycin for treatment of MRSA, preferring nafcillin. However, injected rifampicin – vancomycin combination is preferred by many trusts.
3 reasons why vancomycin side effects may have been exaggerated
1) early preparations of vancomycin were very impure
2) People who reported nephrotoxicity were generally taking other nephrotoxins
3) Ototoxicity is rare
Name an alternative to vancomycin that is used
Teicoplanin
(another glycopeptide)
Mode of action believed to be very similar
When was vancomycin resistance first reported in the UK?
1999
