ID Lecture 9: Pharmacology and Med Chem of Glycopeptides, Lipopeptides, and Polypeptide Antimicrobials | Quizlet

Glycopeptides/Lipopeptides

Vancomycin

Telavancin

Oritavancin

Dalbavancin

Lipopeptide

Daptomycin

Polypeptides

Polymyxin B

Polymyxin E

Bacitracin A

Gramididins

Streptogramins

Dalfopristin/Quinupristin

How do cyclopeptide antibiotics avoid proteolysis?

Cyclization

Use of abnormal amino acids

Vancomycin

Glycopeptide with unusual amino acids and several cross-linked aromatic residues

MOA of Vancomycin

inhibits cell wall biosynthesis by blocking the transpeptidation step of cell wall synthesis

What is the spectrum of activity of Vancomycin?

gram positive

(including MRSA)

Bacterial resistance to Vancomycin

Vancomycin-resistant bacteria have peptidoglycan chains that end in D-ala-D-Lactate instead of D-ala-D-ala

ADRs of Vancomycin

Red man syndrome

Ototoxicity

Nephrotoxicity

Basic structure of Glycopeptide antibiotics

Telavancin

Lipoglycopeptide - semi-synthetic derivative of Vancomycin

MOA of Telavancin

inhibits cell wall biosynthesis and disrupts the cell membrane and integrity

Coverage of Telavancin

skin and soft tissue infections caused by MRSA

Oritavancin

Lipoglycopeptide

Dalbavancin

Lipoglycopeptide

Daptomycin coverage

limited to gram positive

(includes MRSA)

Daptomycin structure

cyclic lipopeptide

(polar head group and lipophilic tail)

MOA of Daptomycin

binds to cell membranes and causes depolarization, which interrupts protein, DNA, and RNA synthesis

What effect do substitutions at R7 have on glycopeptides ?

Increases the half life

Daptomycin spectrum of activity

Complicated skin and soft tissue infections

Staphylococcus bacteremia

Why is Daptomycin NOT used for the treatment of pneumonia?

binds to the surfactant in the lungs which deactivates the antibiotic

ADRs of Daptomycin

Infusion rxns

Muscle pain (elevated CPK)

Eosinophilic pneumonia

Quinupristin/Dalfopristin

Streptogramins

MOA of Quinupristin/Dalfopristin

inhibits protein synthesis by binding to the 50S ribosome and interfering with peptide elongation

Quinupristin/Dalfopristin is a strong inhibitor of what CYP enzyme?

CYP3A4

Polymyxin B Spectrum of activity

Gram - coverage

Polymyxin B MOA

cationic detergent that disrupts bacterial membranes

Polymyxin E MOA

cationic detergent that disrupts bacterial membranes

Bacitracin MOA

inhibits peptidoglycan synthesis at a late stage

Bacitracin spectrum of activity

gram positive

Gramicidin MOA

linear polypeptide antibiotic that disrupts the bacterial cell membrane

Gramicidin spectrum of activity

gram positive organisms