ILE VII: Misc Antimicrobials
What are the two portions of vancomycin and the glyco/lipopeptides?
Glyco dissacharide and cyclic peptide
Which portion of vancomycin and the glyco/lipopeptides contains amino acids of
abnormal structure that cause a reaction in the body?
Cyclic peptide
Where and how does vancomycin bind?
Peptidoglycan via 5 hydrogen bonds
What does vancomycin cover?
MRSA, MSSA, Staph, Strep including PRSP, Bacillis, Listeria, and C. diff
ONLY GP because it is too big to get across the outer membrane of GN
Vancomycin is ___________ dependent and __________.
Time; bactericidal
What is resistant to vancomycin and why?
Enterococci; forms VanA which substitutes lactase (contains an O where the H
should be) where an ala should be in the D-ala-D-ala sequence making impossible
to bind (modified peptidoglycan)
When is vancomycin first line?
MRSA, staph epidermis, strep. pnumoniae, bacillis
- Serious infections caused by GP, beta-lactam resistant bugs
When should we measure troughs to make sure vancomycin is above the MIC?
30-60 minutes before the 4th or 5th dose
How is vancomycin excreted?
Renally; excreted unchanged in urine primarily through GF (not metabolized)
When is oral vancomycin used?
Only for local GI infection; does not absorb systemically
Vancomycin CNS penetration
Fair to poor; large and polar molecule
Vancomycin ADRs
Red man syndrome, phlebitis, nephrotoxicity
Can see some ototoxicity, but rare
Vancomycin Drug Interactions
Non-depolarizing muscle relaxants
AMINOGLYCOSIDES
Cholestyramine- will bind up drug and prevent it from working
What makes the vancins structurally different from vancomycin?
Additional amino sugars on the lipophilic side chain
Vancins MOA
Inhibit cell wall synthesis by binding to peptidoglycan and preventing cell wall
synthesis AND disruption of the cell membrane
How is vancin's MOA different from Vancomycin?
Lipophilic tails anchor the drug in bacterial cytoplasmic membranes to disrupt not
only structure, but function
, What will vancins kill?
MRSA, MSSA, VRSA, VISA, VSE, ENTEROCOCCI
Think of it as an extended spectrum vancomycin
Vancins are effective at _______ MICs compared to Vancomycin
Lower
Which vancin is effective against VRE?
Oritavancin
Which of the following drugs have a half life of about 8 hours?
Vancomycin, Oritavancin, Telavancin, Dalbavancin
Vancomycin, Telavancin
Which of the following drugs have a half life of more than a week?
Vancomycin, Oritavancin, Telavancin, Dalbavancin
Oritavancin, Dalbavancin
Vancins have a ____________ risk of ADRs compared to Vancomycin.
Lesser
Daptomycin MOA
Inserts itself into the cell membrane where it alters the structure of the membrane
creating holes that leak ions. This causes rapid depolarization and eventually cell
death.
Daptomycin is ___________ dependent
Concentration
Daptomycin Spectrum of Activity
Vancomycin resistant enterococci, MRSA, MSSA, VRE
What is active against VRE
Daptomycin and Oritovancin
What is unique about daptomycin?
It is deactivated by lung surfactant, so it should not be used to treat pneumonia
How is daptomycin eliminated?
Renally with very little metabolism
Daptomycin CNS Distribution
Bad
Daptomycin ADRs
Diarrhea, headache, dose dependent CPK elevations (watch with statins)
Daptomycin Drug Interactions
Not a CYP inhibitor or inducer
HOLD STATINS
Name the aminoglycosides.
Tobramycin, Gentamicin, Amikacin
Aminoglycosides MOA
Bind to 30S ribosomal subunit and cause mRNA codon to be misread; interfere with
the initiation complex of 30S and 50S with mRNA
Aminolgycosides will only kill ___________ bacteria.
Aerobic
What are the 3 ways aminoglycosides disrupt biosynthesis?
What are the two portions of vancomycin and the glyco/lipopeptides?
Glyco dissacharide and cyclic peptide
Which portion of vancomycin and the glyco/lipopeptides contains amino acids of
abnormal structure that cause a reaction in the body?
Cyclic peptide
Where and how does vancomycin bind?
Peptidoglycan via 5 hydrogen bonds
What does vancomycin cover?
MRSA, MSSA, Staph, Strep including PRSP, Bacillis, Listeria, and C. diff
ONLY GP because it is too big to get across the outer membrane of GN
Vancomycin is ___________ dependent and __________.
Time; bactericidal
What is resistant to vancomycin and why?
Enterococci; forms VanA which substitutes lactase (contains an O where the H
should be) where an ala should be in the D-ala-D-ala sequence making impossible
to bind (modified peptidoglycan)
When is vancomycin first line?
MRSA, staph epidermis, strep. pnumoniae, bacillis
- Serious infections caused by GP, beta-lactam resistant bugs
When should we measure troughs to make sure vancomycin is above the MIC?
30-60 minutes before the 4th or 5th dose
How is vancomycin excreted?
Renally; excreted unchanged in urine primarily through GF (not metabolized)
When is oral vancomycin used?
Only for local GI infection; does not absorb systemically
Vancomycin CNS penetration
Fair to poor; large and polar molecule
Vancomycin ADRs
Red man syndrome, phlebitis, nephrotoxicity
Can see some ototoxicity, but rare
Vancomycin Drug Interactions
Non-depolarizing muscle relaxants
AMINOGLYCOSIDES
Cholestyramine- will bind up drug and prevent it from working
What makes the vancins structurally different from vancomycin?
Additional amino sugars on the lipophilic side chain
Vancins MOA
Inhibit cell wall synthesis by binding to peptidoglycan and preventing cell wall
synthesis AND disruption of the cell membrane
How is vancin's MOA different from Vancomycin?
Lipophilic tails anchor the drug in bacterial cytoplasmic membranes to disrupt not
only structure, but function
, What will vancins kill?
MRSA, MSSA, VRSA, VISA, VSE, ENTEROCOCCI
Think of it as an extended spectrum vancomycin
Vancins are effective at _______ MICs compared to Vancomycin
Lower
Which vancin is effective against VRE?
Oritavancin
Which of the following drugs have a half life of about 8 hours?
Vancomycin, Oritavancin, Telavancin, Dalbavancin
Vancomycin, Telavancin
Which of the following drugs have a half life of more than a week?
Vancomycin, Oritavancin, Telavancin, Dalbavancin
Oritavancin, Dalbavancin
Vancins have a ____________ risk of ADRs compared to Vancomycin.
Lesser
Daptomycin MOA
Inserts itself into the cell membrane where it alters the structure of the membrane
creating holes that leak ions. This causes rapid depolarization and eventually cell
death.
Daptomycin is ___________ dependent
Concentration
Daptomycin Spectrum of Activity
Vancomycin resistant enterococci, MRSA, MSSA, VRE
What is active against VRE
Daptomycin and Oritovancin
What is unique about daptomycin?
It is deactivated by lung surfactant, so it should not be used to treat pneumonia
How is daptomycin eliminated?
Renally with very little metabolism
Daptomycin CNS Distribution
Bad
Daptomycin ADRs
Diarrhea, headache, dose dependent CPK elevations (watch with statins)
Daptomycin Drug Interactions
Not a CYP inhibitor or inducer
HOLD STATINS
Name the aminoglycosides.
Tobramycin, Gentamicin, Amikacin
Aminoglycosides MOA
Bind to 30S ribosomal subunit and cause mRNA codon to be misread; interfere with
the initiation complex of 30S and 50S with mRNA
Aminolgycosides will only kill ___________ bacteria.
Aerobic
What are the 3 ways aminoglycosides disrupt biosynthesis?
