Cyclic Peptides

Question 0

Transglycosylase

Answer 0

Enzyme responsible for polymerization. Attaches murein monomer into peptidoglycan layer

Question 1

Vancomycin (Vancocin)

Answer 1

Glycosylated hexapeptide chain
Inhibition of cell wall synthesis
Binds D-Ala--D-Ala murein monomer unit=> inhibits TRANSGLYCOSYLASE and Transpeptidase 
Gram (+) bacteria and MRSA
IV
Risk for C. diff overgrowth 
ADR: ototoxicity and nephrotoxicity
Rapid infusion related ADR: red man syndrome and anaphylactoid rxn,

Question 2

Transpeptidase

Answer 2

Enzyme that acts at D-Ala–D-Ala and form cross linking of pentaglycine units

Question 3

Daptomycin (Cubicin)

Answer 3

Cyclic lipopeptide
Binds to cell membrane and causes depolarization
Gram(+) bacteria (skin infections)
Slow IV infusion
ADR: muscle pain and weakness, increased SCr phosphokinase

Question 4

Colistin (Coly-Mycin)

Answer 4

Cyclic lipopeptide with DAB
Cationic Abx that binds to anionic bacterial outer membrane and disrupts membrane integrity
Gram (-) especially P. Aeruginosa
IV or oral inhalation
ADR: nephrotoxicity (especially with similar toxicity drugs I.e. aminoglycosides), neuromuscular blockade

Question 5

Bacitracin (Baciim)

Answer 5

Metallo-antibiotic
Interferes with dephosphorylation of phospholipid carrier (bactoprenol) in cell wall synthesis
Gram(+) bacteria
ADR: used topically b/c of multiple toxicities (neuro, nephro, and bone marrow)
DDI: metal chelators decrease bacitracin activity

Question 6

Mupirocin (Bactroban)

Answer 6

Lipid ester, not cyclic but it is natural
Binds specifically to tRNA synthetase and prevents incorporation of insoleucine into bacterial proteins
Gram (+) and (MRSA)
Topical

Question 7

Vancomycin Abx resistance mechanisms

Answer 7

Alteration of target preventing drug binding: VRE=> D-Ala–D-Ala altered to D-Ala–D-Lactate or D-Ala–D-Ser
Gene transfer: MRSA transferred gene to VRE giving rise to VRSA
Cell wall thickening (decreased access of drug to binding site): VISA

Question 8

Daptomycin mechanism of bacterial resistance

Answer 8

Cell wall thickening: decreased drug access to binding site

Increased Lysyl-phosphatidylglycerol synthetase: increased repulsion

Question 9

Coilstin mechanism of bacterial resistance

Answer 9

Changes in LPS layer or phosphate content: decrease drug binding

Question 10

Mupirocin mechanism of bacterial resistance

Answer 10

Rare alteration of drug target: bypass synthetase that drug targets.