Exam 1-Cushman Lecture 2- Vancomycin + Lipoglycopeptides

Question 1

What kind of antibiotic is vancomycin?

Answer 1

Nonribosomal glycopeptide

Question 2

What are the 2 glycopeptide antibiotics in clinical use?

Answer 2

Vancomycin

Teicoplanin

*note that only vancomycin is used in the US

Question 3

What is the moa of vancomycin?

Answer 3

-binds to the peptidyl side chain D-ala-D-ala terminus in the peptidoglycan precursor (before cross-linking)
-high affinity binding of vancomycin to the substrate inhibits the transpeptidase reaction needed for cross-linking
-also inhibits the transglycosylation stem in peptidoglycan synthesis

*note that vancomycin forms a cup around a peptidoglycan which prevents linkage with other peptidoglycans

Question 4

How does the moa of vancomycin compare to the beta lactams?

Answer 4

The mechanism is similar in terms of the reaction that is inhibited, but the mechanisms of inhibition are different

Question 5

What is the antibiotic spectrum of vancomycin?

Answer 5

Primarily bactericidal
Active against Gram +

no Gram - bacteria are susceptible to vanc

Question 6

Use of which antibiotic in livestock led to the first vancomycin-resistant enterococcal infections appearing?

Answer 6

Avoparcin
-now banned

Question 7

What is the mechanism of resistance against vancomycin?

Answer 7

Mutation of the peptidoglycan cell wall precursor from D-Ala-D-Ala to D-Ala-D-lactate

-note that this is a mutation that changes NH to an O
-hydrogen bonding normally occurs with NH but cannot with O

*vancomycin has 1000 times less affinity for the D-Ala-D-Lactate precursor and ultimately does not inhibit the transpeptidase

Question 8

What is the route of administration of vancomycin?

Answer 8

IV

-does not get high enough blood levels when po

Question 9

What are the 2 primary uses of vancomycin?

Answer 9

-C diff (2nd line after metronidazole)
-MRSA

Question 10

What are the main toxic effects of vancomycin?

Answer 10

-Hypersensitive response (red rash, anaphylaxis)
-Nephrotoxicity
-Ototoxicity

Question 11

Generally, what is a lipoglycopeptide antibiotic?

Answer 11

Vancomycin molecules with lipophilic appendages synthetically attached

Question 12

What are the lipoglycopeptides?

Answer 12

Oritavancin
Telavancin
Dalbavancin

Question 13

What is the moa of oritavancin?

Answer 13

Inhibits transpeptidation and transglycosylation
-disrupts the membrane of gram-positive bacteria

Question 14

What is the spectrum of antibacterial activity of oritavancin?

Answer 14

Active against a broad spectrum of gram-positive bacteria
-includes MRSA

Question 15

What is the moa of telavancin?

Answer 15

Like vancomycin, binds the D-Ala-D-Ala terminus of the peptidoglycan in the growing cell wall

-inhibits transpeptidation and transglycosylation

Question 16

What is the spectrum of antibacterial activity of telavancin?

Answer 16

Gram + infections

-treats MRSA

Question 17

Which lipoglycopeptide antibiotic is a second-generation?

Answer 17

Dalbavancin

Question 18

What is the moa of dalbavancin?

Answer 18

Identical to vancomycin

-Binds to D-Ala-D-Ala residue on growing peptidoglycan chains

-prevents transpeptidation and transglycosylation
(therefore prevents peptidoglycan elongation and cell membrane formation)

Question 19

What is the spectrum of antibacterial action of dalbavancin?

Answer 19

Active against a broad spectrum of Gram + bacteria

Includes: MRSA and MRSE

Question 20

What are the half-lives of vancomycin, telavancin, dalbavancin, and oritavancin?

Answer 20

Vancomycin: 4-6h

Telavancin: 7-9h
Dalbavancin: 204h
Oritavancin: 245h

*D and O can be used as single-dose regimens