Other Cell Wall Inhibitors And Daptomycin

Question 1

What is the MOA of Vancomycin?

Answer 1

Binds to d-alanyl-d-alanine peptidoglycan terminus.
Inhibits polymerization reactions.
Prevents cross-linking of peptidoglycan polymers inhibiting peptidoglycan elongation.
Cell susceptible to lysis + cell membrane also damaged.

Question 2

What is the resistance of vancomycin?

Answer 2

Modification of D-ala-D-ala binding site to d-lactate.
Decreased affinity for target site –> loss of activity.
Bacteria with thickened CW and too many D-ala-D-ala residues.
Dead end binding sites.

Question 3

What is the spectrum of activity?

Answer 3

G+ bacteria including MRSA.
Synergistic effect with gentamycin and streptomycin against E faecium and E faecalis

Question 4

What are the main clinical uses?

Answer 4

MRSA, C. Difficile colitis, + gentamicin for enterococcal endocarditis

Question 5

What are the major gaps in the spectrum?

Answer 5

All gram - bacilli, mycobacteria

Question 6

What are the pharmacokinetics?

Answer 6

Poor oral absorption, wide distribution - variety of body fluids
90% is excreted by glomerular filtration. Half-life is 6 hours.

Question 7

What are important adverse effects?

Answer 7

Nephrotoxicity, ototoxicity and DRESS. Red man syndrome if administered too quickly.

Question 8

What are the indications of Teicoplanin?

Answer 8

Complicated soft tissue infection, complicated UTIs, Joint and bone infections, surgical prophylaxis.

Question 9

What is the mechanism of action of Fosfomycin?

Answer 9

Drug transported into bacterial cell by glucose-6-phosphate transport systems. Inhibits enolpyruvate transferase, produces UDP precursor, inhibits CW synthesis.

Question 10

Indications for fosfomycin?

Answer 10

Uncomplicated UTIs in Women. Prophylaxis prior to transurethral and diagnostic procedures in men

Question 11

Adverse effects of daptomycin?

Answer 11

Myopathy, allergic pneumonitis - inflammation of the alveoli, nephrotoxicity