Anti-microbials 1 Flashcards
What are the targets of the Bacteria Cell for anti-microbials?
There are three main differences between bacteria and human cells which form the basis of Antimicrobial therapy;
- Peptioglycan layer of Cell Wall
- Bacterial Ribosomes are different to Eukaryotic Ribosomes
- DNA Gyrase and other prokaryote-specific enzymes
What are the six broad classes of Antimicrobial agents?
i) Inhibitors of Cell Wall Synthesis
ii) Inhibitors of Protein Sythesis
iii) Inhibitors of DNA Synthesis
iv) Inhibitors of RNA Synthesis
v) Cell Membrane Toxins
vi) Inhibitors of Folate Metabolism
Which antibiotics are Inhibitors of Cell Wall Synthesis?
- Beta-lactam antibiotics
2. Glycopeptides
What are beta-lactams and how do they work?
Transpeptidases i.e. penicillin binding proteins, are responsible for forming peptide cross-links between the “peptidoglycan precursors” giving the cell wall rigidity
- > Beta-lactam’s are a structural analogue of the enzyme substrate to Transpeptidases
- > As a result, they inactivate these enzymes from functioning
- > The daughter cell wall is weak and lyses with osmotic pressures
What are Glycopeptides and how do they work?
Large molecules which bind to the end of the peptide chains, preventing Transpeptidases and Transglycosidease’s from binding
-> Daughter cells have weak cell wall’s which lyse with osmotic pressures.
What kind of bacteria are Beta-lactams and glycopeptides inefficient against?
- Beta-Lactams are inefficient against bacteria that lack peptidoglycan cell walls i.e. Mycoplasma or Chlamydia
- Glycopeptides are ineffective against Gram-ve organisms.
REMEMBER Gram-ve’s have an “outer membrane” over the peptidoglycan, as a result, the Glycopeptides cannot cause an effect
Give examples of beta lactams
- Penicillins
- Cephalosporins
- Carbapenems
Give 4 examples of Penicillins
Penicillin
- > Effective against Gram +VE’s i.e. Streptococci and Clostridia
- > Broken down by Beta Lactamase (therefore ineffective against S Aureus)
- IV Penicillin G (Benzylpenicillin), Oral Penicillin V (Phenoxymethylpenicillin)
Basically you only use Oral Penicillin V in Strep Throat. Anything more serious you use IV Benzylpenicillin and step down to Oral Amoxicillin (better drug delivery)
Flucloxacillin
- > Similar to Penicillin but less active
- > STABLE TO BETA LACTAMASES therefore used in S. Aureus
Amoxicillin
- > Broad spectrum Pencillin
- > Also effective against Enterococci and some Gram -VE’s
- > Broken down by Beta Lactamase (Ineffective against S Aureus and many Gram - VE’s i.e. E.Coli)
Piperacillin Similar to Amoxicillin -> Covers for Pseudomonas (i.e. Hospital Acquired Pneumonia) -> Covers other non-enteric Gram -ve's -> Broken down by Beta Lactamases
To overcome this issue of Beta Lactamase’s, what two things were done?
i) Antibiotics can be given with Beta-Lactamase Inhibitors.
- > Clavulanic Acid (+ Amoxocillin = Co-Amoxiclav i.e. Augmentin)
- > Tazobactam (+ Amoxocillin = Tazocin)
ii) Cephalosporins were born
Give examples of cephalosporins of each generation
More stable against beta lactamases than penicillins
First Generation
-> Cephalexin
Second Generation
-> Cefuroxime ( similar to Co-Amoxiclav but less active against anaerobes)
Third Generation
- > Cefotaxime
- > Ceftriaxone (Ass. with C.Difficile)
- > Ceftazidime (Anti-Pseudomonas!)
As the generations increase in cephalosporins…
they become more effective against gram negative organisms and less effective against gram positive
What has the increased use of Cephalosporins led to?
led to the development of ESBL - Extended Spectrum Beta-Lactamases i.e. Cephalosporin Resistant Organisms
What are Carbapenems?
- > Stable to ESBL Enzymes
- > Meropenem, Imipenem, Ertapenem
However, the widespread use of Carbapenems has led to the rise of Carbapenemase enzymes
-> Multi drug resistant Acinetobacter and Klebsiella
What are the Beta Lactam Key Points? (5)
-> Relatively non-toxic
-> Renally Excreted
CAUTION in patients with renal impairment
-> Short half life
Mutliple daily doses may be required
-> Can cross inflamed meninges, but not INTACT BBB.
Ceftriaxone used in Meningitis
-> Cross-allergenic
10% of those with a penicillin allergy react to cephalosporins/carbapenems
What are examples of 2 commonglycopeptides/
- > Vancomycin
- > Teicoplanin
