Cell wall synthesis inhibitors: Cephalosporins Flashcards
What are the bacterial cell walls made of?
Peptidoglycan- made of segments of NAG and NAM in alternating patterns
What protrudes from the peptidoglycan chain?
Tetrapeptide chains from the NAM subunit
What is the role of the tetrapeptide chains protruding from the peptidoglycan chain?
The link to pentapeptide chains from neighbouring strand through transpeptidation
What enzyme allows transpeptidase to occur?
Penicillin binding protein (PBP)
How do beta lactams (including cephalosporins) inhibit bacteria?
They have a similar structure to the tetrapeptide chains, so they bind to the PBP and permanently disable PBP= failed cross linking + decreased stability
How has S.aureus developed resistance against beta-lactams?
It evolved an enzyme called beta lactamases that break down the beta lactam ring within the antibiotic
How did we overcome the development of beta lactamase?
By adding agents such as clavulanic acid that bind to beta lactamases that inactivate them or using new kinds of beta lactams e.g. methicillin that has a large side chain that wouldn’t fit into beta lactamase
How did S.aureus further develop resistance?
Mutated to create a new PBP site mutation meaning antibiotics wouldn’t fit in the PBP enzyme
What are the S.aureus with a new PBP site called?
MRSA- methicillin resistance staphyloccous aureus
How do we treat MRSA?
We rely on reserve antibiotics that belong to the glycopeptide antibiotics e.g. vancomycin and teicoplanin
How are cephalosporins classified?
By generations which relates to their usage profile (not age related but spectrum related)
Which generation has the narrowest spectrum?
The 1st. It increases as you increase the generations
What is an example of a 1st gen cephalosporin?
Cephalexin and cefazolin
What are 1st generation cephalosporins effective against?
- Streptococci and staphylococci that cause skin infections. (Also taken prophylactically to prevent surgical infections)
- A few gram negative bacteria that cause UTI’s like: proteus mirabilis, e.coli and klebsiella pneumoniae
What is the problem with 1st gen ceph’s and staphylococci?
They are only effective against those that haven’t developed beta-lactamases yet
What are some examples of 2nd gen cephalosporins?
Ceaclor, cefprozil, cefuroxime, cefotetan and cefoxitin
What ‘upgrade’ do 2nd gen have?
- They are more resistant to beta lactamase
- Have comparable effectiveness for treating gram positive bugs+ cover more gram negative bugs
What are some examples of 3rd gen cephalosporins?
Cefixime, ceftriaxone, cefotaxime and ceftazidime
What are 3rd gen ceph’s sensitive against?
Mainly gram-negative bacteria (at the cost of gram positive) such as haemophilus influenzae, pneumocooci, neisseria species
Why are 3rd gen ceph’s 1st line for bacterial meningitis?
Because they cross the blood brain barrier
What other disease are 3rd gen cephs often used for?
Penicillin resistant neisseria gonorrhoeae
What is ceftazidime particularly known for being effective against?
Pseudomonas aerguinosa
What is the main medication in 4th gen cephs?
Cefepime- which is effective against gram negative and gram positive and is effective against pseudomonas and crosses the BBB
What is Cefepime often used to treat?
Same infections as 3rd gen such as meningitis. Also used to treat nosocomial bacterial infections
