Vancomycin Flashcards
What produces Vancomycin via fermentation?
Streptomyces orientalis
Amycolatopsos orientalis
How does Vancomycin work?
Inhibits Gram + cell wall biosynthesis
How does Vancomycin inhibit?
Binds to side chain D-alanyl terminus before cross linking
Are gram - bacilli or mycobacteria susceptible to Vanco?
No
What level of MIC is needed to be considered susceptible for Vanco?
4ug/mL
What is the last line of defense against hospital aquired multidrug resistant staph and strep infections?
Vancomycin
What mutation is causing the resitance to vancomycin?
Peptidoglycan wall formation switch from D-Ala D-Ala to D-Ala D-lactate
Side effect of Vanco?
Hypersensitive red skin rash
Potential anaphylaxis
Toxicity to Vanco?
Nephrotoxicity due to high concentration
How many membered are the macrocyclic lactones?
14 membered
How are macrolide antibiotics produced?
Sequential addition of proprionate groups
pKa of amine in erythromycin?
8.8
What is translocation?
Peptodyl-tRNA is shifted from the A site to the P site
How do macrolides work?
Binding reversibly to the P site of the bacterial ribosome
Where do macrolides accumulate?
Leukocytes
Why is it good that macrolides accumulate in leukocytes?
They are transported into the site of infection
Macrolide binding mainly invovles what?
Bacterial 23S RNA
Function of lactone ester hydrolase?
Induce to degrade macrolides via hydrolysis of macrocycle
RNA methylase will have what effect on resistance of erythro?
Inhibits binding of macrolides to 50S subunit
Mutation of adenine to gunanine at site A2058 results in what?
Reduction in binding of erythro and clarithromycin to 23 S ribosomal RNA
What will the result of a drug efflux pump be?
Resistance to erythro
Which organisms exhibit intrinsic resistance to macrolides?
Pseudomonas spp.
Enterobacter spp.
In macrolyides acidic conditions affect which group?
6-OH group
If the macrolide group 6-OH is transformed into a ketal what is the result?
It’s inactive
What is a way to work around the acidity problem with macrolides?
USe Clarithromycin which has a 6-OCH3 that blocks ketal formation
Besides Clarithromycin what is another alternative to skirt the acid problem of macrolides?
Azithromycin
Why with Azithromycin negate the acid problem?
Replaces the C-9 ketone makine ketal formation impossible
Main route of erythromycin metabolism?
Demethylation in the liver
Main elimination route of erythro?
Bile
Small part in urine
Half life of erythro?
1.5 hours
Erythro and Clarithro effect on CYP3A?
Bind and inhibit
Dirithromycin effect on P450 isozymes?
Reduced capacity to inhibit
Macrolides that doesn’t have any potential drug interactions?
Azithromycin
Effect of macrolides on GI system?
Stimulate GI motor activity and can cause vomiting, gastric cramps, and abdominal pain
two rare occurances due to macrolide use?
Stevens-Johnson syndrome
Toxic epidermal necrolysis
Long term use of macrolides can cause what reversible problem?
Cholestatic hepatitis
Gone after termination of drug use
What can erythro effect in children whose mothers took it while in late stages of pregnancy?
Pyloric stenosis
Where is erythro most effectively absorbed?
Tissues and phagocytes
What is erythromycin estolate?
Prodrug of erythromycin
Benefit of Erythromycin estolate?
More lipophilic
Increase oral absorption
What is erythromycin estolate used to treat?
Group A beta hemolytic strep
Primary Syphillis
Alpha hemolytic strep
What is erythromycin ethyl succinate?
Prodrug of erythromycin
What is more effective against Haemophilis influenzae than clarithromycin
Clarithromycin metabolite 14-(R) hydroxy
How many members in Azithromycin ring?
15, due to removal of Carbon 9 to prevent ketal formation
Half life of Azithromycin?
68 hours
Which elements can interefere with Azithromycin absorption into tissues?
MAgnesium and aluminum
Major route of elimination for Azithromycin?
Biliary
What bacteria does Azithromycin kill better than eyrthro or clarithro?
Gram -
