Antibiotic resistance - additional revision powerpoint (c) Flashcards
What are the different types of beta lactams?
Penicillins (-cillin)
Carbapenems (-penem)
Cephalosporins (all start with cef- ceph-)
Monobactam (aztreonam is the only approved)
Why is the activity of different beta lactam subclasses different?
Have unique specific side chains attached to the core
What can be used to counteract beta lactam resistance due to beta lactamases?
Clavulanic acid
Sulbactam
Tazobactam
Avibactam
Bind to and inhibit beta lactamases.
How do the mechanisms of resistance to beta lactams vary between gram negative and gram positive bacteria?
Gram pos cocci - mutated PBP - PBP2A - reduced affinity
Gram neg - Beta lactamase enzymes
What are some examples of macrolides?
What is the namine stem?
-thromycin
Erythromycin (original macrolide)
Clarithromycin
Azithromycin
How does resistant to macrolides tend to spread?
Reliant on horizontal transfer of the ermC gene
Normally found on plasmids or transposons (jumping genes), transferred vie conjugation (pilli channels) between strains and species.
What bacterial strain is best known for expressing the ermC gene for resistance against macrolides?
Staphylococcus aureus.
What are some different examples of fluoroquinolones?
What is there naming stem?
-floxacin
Ciprofloxacin
Levofloxacin
Maxifloxacin.
‘flouro’ as flourine molecule at position 6 greatly improves potency
How does the mechanism of action of fluoroquinolones vary between gram negative and gram positive bacteria?
In both targets DNA gyrase and topoisomerase IV
Gram neg - DNA gyrase is the main target
Gram pos - topoisomerase IV is the main target.
What are the key mechanisms of fluoroquinolone resistance?
Mutatsion in gyraA or gyraB gene alter DNA gyrase
results in Reduced affinity for the fluoroquinolone antibiotic for this enzyme
Mutation in parC or parE gene in Topo IV, reduces affinity as a drug target.
What is the naming and some examples of aminoglycosides?
End in mycin, micin or cin (NOT thro—).
Examples include: gentamicin, tobramycin, amikacin, kanmycin, streptomycin
How are aminoglycosides given clinically?
Always given alongside another antibiotic to broaden the spectrum of coverage or as an adjunct therapy
Adminstered parenterally (via IV)
What is the mechanism of action of aminoglycosides?
Binds the aminoacyl site of 16s ribosomal RNA within the 30S ribosomal subunit
-Induces codon misreading and the mistranslation of proteins which results in incorrect amino acids and dysfunctional proteins. particularly damaging in the bacterial cell membrane
- Blocks further translation and elicits premature termination
- Blocks initiation of protein synthesis.
What are the different mechanisms of resistance to aminoglycosides?
AMEs - amingolycoside modifiying enzymes
N-acetyltransferases - acetylates an amino group using acetyl-CoenzymeA
O-nucleotidyltransferases = transfer an adenyl group from ATP to a hydroxy group
O-phosphotransferases - uses ATP to phosphrylate a hydroxy group.
Modified drug fails to bind to bacterial target
