C17

Question 1

Gylycopeptides (3)

Answer 1

Teicoplanin
Oritavancin
Vancomycin

Question 2

Glycopeptides MOA

Answer 2

• Bactericidal glycoprotein
• Bind to d-Ala-d-Ala terminal of peptidoglycan –> inhibit transglycosylation –> prevent elongation of the peptidoglycan chain and interferes with cross-linking.

inhibit cell wall synthesis

Question 3

Glycopeptide resistance development
give examples

Answer 3

• bacterial replacement of the terminal d-Ala by d-lactate –> vancomycin binding site affinity is decreased
• VRE and VRSA

Question 4

Glycopeptides indications

Answer 4

Gram positive activity includes:

• MRSA
• PRSP
• Narrow spectrum
• used for serious infections by G+’s (ex.MRSA)
• used in combination with 3rd Gen. Cephalo. (ex. Ceftriaxon) against PRSP
• used against C.difficile

Question 5

Glycopeptides Pharmacokinetics

Answer 5

• PARENTERAL –> penetrates most tissues
• renal elimination ( unchanged in the urine)

oral for C.difficle !

Teicoplanin long T1/2 (45-70 hr)

Oritavancin: I.V , very long T1/2 (>10days)

Question 6

Glycopeptides administration

Answer 6

• Orally for C.difficle only (bacterial enterocolitis)
• Parenterally

Question 7

Glycopeptides side effects

Answer 7

• chills
• Fever
• Phlebitis
• ototoxicity
• Nephrotoxicity
• Red Man Synd.

Question 8

What is red man synd?

Answer 8

diffuse flushing as a result of histamine release after RAPID glycopeptides I.V. infusion

Question 9

Lipopeptides AB example

Answer 9

Daptomycin

Question 10

Daptomycin spectrum

Answer 10

• similar to vancomycin
• but also active against vancomycin-resistant strains of enterococci and staphylococci (VRE, VRS)

Question 11

Daptomycin MOA

Answer 11

The drug inserts into the cytoplasmic membrane –> K+ leak , –> cell death

Destabilizes membrane

Question 12

Daptomycin pharmacokinetix

Answer 12

Daptomycin is eliminated via the kidney

Question 13

Daptomycin SE

Answer 13

• myopathy

(monitor. Creatine phosphokinase CPK weekly)

Question 14

Peptide AB example

Answer 14

Bacitracin

Question 15

Bacitracin MOA

clinical use

Answer 15

interferes with a late stage in cell wall synthesis in G+’s

• minor infections by skin or mucous surfaces (cuts/burns)
• c.difficile (alternative to metronidazole)

Question 16

Bacitracin administration and SE

Answer 16

• marked nephrotoxicity
• it is limited to topical use (because of the kidney)

Question 17

What about Mupirocin ?

Answer 17

• it is a natural product from Pseudomonas Fluorescens
• It acts on G+ cocci
• Binds to isoleucyl-tRNA synthetase –> inhibits protein synthesis

Question 18

Mupirocin Pharmacokinetix and clinical use

Answer 18

* when used topically (it is not absorbed):

• staphylococcal impetigo ( also MRSA)
• beta-hemolytic streptococci (s.pyogenes)

* when used intraNasally:
- eliminate staphylococcal carriage by patients and medical personnel

Question 19

Mupirucin Toxicity?

Answer 19

• Local itching
• burning sensations
• rash
• erythema
• contact dermatitis.

Question 20

fusidic acid MOA

Answer 20

• inhibits bacterial protein synthesis (inhibits elongation factor g)

Question 21

fusidic acid

spectrum

clinical use

Answer 21

• gram +
• aerobes
• anarobes
• topical > skin infections (cellulitis, impetigo) , conjuctivitis
• systemic > MRSA infections

Question 22

fusidic acid administration

Answer 22

Topical: cellulitis, impetigo, conjuctivitis

parenteral > MRSA

Question 23

fusidic acid toxicity

Answer 23

Hepatotoxic with systemic use