Gram Positive Antibiotics

Question 1

What are the glycopeptides?

Answer 1

•  Vancomycin 
•  Teicoplanin 
•  Dalbavancin 
•  Telavancin 
•  Oritavancin

Question 2

What is the MOA of vancomycin?

Answer 2

Inhibits bacterial cell wall synthesis at a site different than β-lactams at the second stage of synthesis.

Binds firmly to D-alanyl-D-alanine portion of cell wall precursors to prevent cross-linking and further elongation of peptidoglycan; weakens cell wall.

Question 3

What is the pharmokinetic activity of vancomycin?

Answer 3

Time-dependent bactericidal activity (kills bacteria slowly)

Bacteriostatic VS enterococcus

Question 4

How are VRE and VRSA resistant to vancomycin?

Answer 4

Modification of D-alanyl-D-alanine binding site of peptidoglycan
! Terminal D-alanine replaced by D-lactate
! Loss of critical hydrogen bond
! Loss of antibacterial activity

Question 5

How is VISA (Vancomycin Intermediate S. aureus) resistant to vancomycin?

Answer 5

Thickened cell wall

Question 6

What is the spectrum of vancomycin activity?

Answer 6

Gram-positive bacteria
! MSSA/MRSA
! Coagulase-negative staphylococci*
! Streptococcus pneumoniae (including PRSP), viridans streptococcus, Group streptococcus
! Enterococcus spp.
! Corynebacterium, Bacillus. Listeria, Actinomyces
! Clostridium spp. (including C. difficile), Peptococcus, Peptostreptococcus

NO GRAM-NEGATIVE ACTIVITY

Question 7

How is vancomycin administered?

Answer 7

Must be IV

Oral only for C. difficile

Question 8

What is the elimination of vancomycin dependent upon?

Answer 8

Elimination half-life depends on renal function

Question 9

Vancomycin SE

Answer 9

Red-Man Syndrome
! Flushing, pruritus, erythematous rash on face, neck, and upper torso within 5 to 15 minutes of starting infusion (His release)
! Related to RATE of intravenous infusion; doses should be infused over at least 60 minutes

Otoxicity

Nephrotoxicity

Question 10

What is the MOA of dalbavancin?

Answer 10

D-ala D-ala binding, inhibiting cross-linkage similar to vancomycin. However, it has a lipid moiety that anchors to cell membrane.

More potent and cidal than vancomycin

Question 11

What is the spectrum of dalbavancin activity?

Answer 11

MRSA
VISA
vanB and vanC VRE (NOT vanA though)
Bacillus, Listeria, Corynebacter
MRSE

Question 12

How is dalbavancin administered?

Answer 12

IV only

Question 13

What are the main uses for telavancin?

Answer 13

Complicated SSSI

Pneumonia (hospital acquired)

Question 14

What are the main uses for oritavancin?

Answer 14

MSSA, MRSA, Enterococcus, Strep possible Bacillus anthracis

Question 15

What is the MOA of oritavancin?

Answer 15

Same as vancomycin but it also disrupts the cell membrane

Question 16

What are the Oxazolidinones drugs?

Answer 16

Linezolid

Tedizolid

Question 17

What is the MOA of linezolid?

Answer 17

Binds to the 50S ribosomal subunit near the surface interface of 30S subunit – causes inhibition of 70S initiation complex (unique binding site), which inhibits protein synthesis

Question 18

What are the pharmokinetics of linezolid?

Answer 18

Time dependent Bacteriostatic

Question 19

What is the spectrum of linezolid?

Answer 19

MSSA
MRSA
VRSA
E. faecium/E. faecalis and VRE
Some mycobacteria activity

Question 20

What is the CSF penetration of linezolid?

Answer 20

Decent (30%)

Question 21

Does linezolid dose have to be adjusted for renal failure?

Answer 21

No

Question 22

How is linezolid administered?

Answer 22

Oral or IV

Question 23

What is the oral bioavailability of linezolid?

Answer 23

100%

Question 24

What are the clinical uses of linezolid?

Answer 24

Use reserved for serious/complicated infections caused by resistant gram-positive bacteria:
! VRE bacteremia, NOT urinary tract infections
! Complicated skin and soft tissue infections due to
MSSA, MRSA or Streptococcus pyogenes
! Nosocomial pneumonia due to MRSA

Question 25

What is the major drug interaction of linezolid?

Answer 25

Serotonin syndrome with SSRIs/MAOIs

Question 26

Linezolid SE

Answer 26

Peripheral neuropathy

Thrombocytopenia or anemia

Question 27

What is an advantage of tedizolid over linezolid?

Answer 27

More potent and has no SSRI interaction like linezolid

Question 28

Daptomycin MOA

Answer 28

Binds to bacterial membranes → rapid depolarization of membrane potential → inhibition of protein, DNA, and RNA synthesis

Question 29

Daptomycin pharmokinetics

Answer 29

Concentration-dependent bactericidal activity

Question 30

Daptomycin Spectrum

Answer 30

! Methicillin-Susceptible, Methicillin-Resistant AND Vancomycin-Resistant Staph aureus* and coagulase-negative staphylococci
! Streptococcus pneumoniae (including PRSP), viridans streptococcus, Group streptococcus
! Enterococcus faecium AND faecalis (including VRE)

Question 31

Are dose adjustments required for daptomycin in renal failure patients?

Answer 31

Yes

Question 32

What is daptomycin ineffective in treating?

Answer 32

Pneumonia. It is inactivated by surfactant

Question 33

Daptomycin SE

Answer 33

Myopathy and CPK elevation

Question 34

What are the unique features of Quinupristin-Dalfopristin and its MOA?

Answer 34

They are both bacteriostatic protein synthesis inhibitors but together, they become bactericidal.

Question 35

What is the MOA of Quinupristin-Dalfopristin?

Answer 35

Dalfopristin enhances binding of quinupristin. Inhibits peptidyltransferase.
Quinupristin prevents elongation of polypeptide chain & causes incomplete chain release.

Question 36

What are the SE of Quinupristin-Dalfopristin?

Answer 36

Severe GI intolerance

Question 37

What is the spectrum of Quinupristin-Dalfopristin?

Answer 37

Gram Positive Organisms

Question 38

How is daptomycin resisted?

Answer 38

Alteration of membrane binding