L29- Vancomycin, Daptomycin, Bacitracin

Question 1

Vancomycin:

• (1) definition / origin
• mainly affects (2) bacteria- (3) explain why not against others

Answer 1

1- bacterial glycoprotein

2- Gram+ and MDR bacteria (specifically penecillin resistant)
3- too large to cross Gram- outer membrane

Question 2

Vancomycin works by binding (1) region of (2) in order to prevent (3). For bacterial resistance to vancomycin, (4) or (5) would have to occur, as vancomycin is not susceptible to (6).

Answer 2

1- D-Ala-D-Ala terminus
2- peptidoglycan pentapeptide
3- bacterial cell wall synthesis and peptidoglycan formation

4- modification of D-Ala-D-Ala binding site
5- plasmid-mediated change in drug permeability
6- β-lactamase

Question 3

Vancomycin:

• (1) and (2) are the main uses in monotherapy
• (3) and (4) are the main uses in combination therapy

Answer 3

1- serious infections caused by β-lactam resistant Gram+ organisms (eg. MRSA)
2- Gram+ infections in patients with severe penicillin allergy

3- (+ aminoglycoside) empiric Tx for infective endocarditis
4- (+ aminoglycoside) PRSP Tx (penicillin resistance Strep. pneumoniae)

Question 4

Vancomycin is the drug of choice for….. (include route of administration and its importance)

Answer 4

• Staph. enterocolitis
• antibiotic-associated pseudomembranous colitis (C.diff)

given orally –> poor oral bioavailability –> stays in GIT to affect gut infection

Note- also used against MRSA

Question 5

Vancomycin Pharmacokinetics:

• (1) route of administration
• reaches (2) body cavity when inflamed
• (3) route of elimination

Answer 5

1- slow IV fusion, 60-90 mins /// except some gut infections –> poor oral bioavailability so useful when given po

2- CSF (meningitis- only Tx, not prophylaxis)

3- 90-100% kidneys

Question 6

Vancomycin AEs:

• (1) is unique effect, explain in what situations
• (2) common minor AEs
• (3) can occur due to drug accumulation

Answer 6

1- ‘red man’ / ‘red neck’ syndrome = flushing of face and torso due to rapid IV infusion

2- fever, chills, phlebitis at injection site

3- nephrotoxicity, ototoxicity (monitor kidney function)

Question 7

Daptomycin:

• bacterio-(static/cidal)
• effective against (2) bacteria
• ineffective against (3) bacteria or (4) infections

Answer 7

1- bacteriocidal
2- resistant Gram+ organisms (eg. MRSA, VRSA, enterococci)

3- Gram- bacteria
4- pneumonias: even if Gram+, inactivated via surfactant

Question 8

describe the MOA of daptomycin and its importance in terms of clinical uses

Answer 8

(novel MOA –> useful against MDR bacteria)

1) binds cell membrane via Ca-dependent insertion of lipid tail
2) results in depolarization of cell membrane via K+ efflux –> cell death

Question 9

list the main uses for daptomycin

Answer 9

• severe infections caused by MRSA, VRE (vancomycin resistant enterococcus
• complicated skin infections caused by susceptible S. aureus

Question 10

Daptomycin:

• (1) route of administration
• may accumulate in patients with (2)

Answer 10

1- IV

2- renal insufficiency

Question 11

Daptomycin AEs:

• (1) common AEs
• (2) indicates discontinuation of (3) drug

Answer 11

1- nausea, constipation, HA, insomnia

2- elevated creatine phosphokinase
3- statins (if co-administered)

Question 12

Bacitracin:

• MOA interferes with (1), and it (2) is important feature that relates to its use
• effective against (3) bacteria
• (4) are the main AEs, therefore route of administration is usually (5)

Answer 12

1- late stage cell wall synthesis
2- unique mechanism —> no cross-resistance

3- Gram+ organisms

4- nephrotoxicity
5- topical (to avoid Gram+ infections)