lipoglycopeptides

Question 1

Intro

Answer 1

The lipoglycopeptides were developed to address the continued need for antibiotics with activity against resistant Gram-positive (VRE, MRSA, VISA)

Question 2

MOA

Answer 2

All lipoglycopeptides interfere with the polymerization and cross- linking of peptidoglycan by binding to the D-Ala-D-Ala terminus. The lipid side chain anchors the drugs to the cell membrane and concentrates the drug at the site of action.

Oritavancin and telavancin (not dalbavancin) also appear to bind to bacterial membranes and insert their lipophilic tails into the cell wall to form a transmembrane channel (like daptomycin) causes leakage of cellular contents and rapid depolarization of the membrane potential leading to inhibition of protein, DNA, and RNA synthesis, resulting in bacterial cell death.

Question 3

Drugs in class

Answer 3

Telavancin
Dalbavancin
Oritavancin

Question 4

Mechanisms of resistance

Answer 4

Alteration in peptidoglycan terminus

Question 5

Spectrum of activity

Answer 5

Gram positive aerobes
- Enterococcus faecium AND faecalis - some strains of VRE display resistance to telavancin and dalbavancin
-Staphylococcus aureus and CNS (MS, MR, VI; oritavancin also displays activity against VRSA)

Question 6

Pharmacology

Answer 6

All parenterally available only
Concentration-dependent bactericidal activity, where the AUC/MIC is the best predictor of efficacy

Question 7

Distribution

Answer 7

all agents distribute fairly well into tissues including skin and lung tissue; all display poor CSF penetration and are 90% protein bound

Question 8

Elimination

Answer 8

Telavancin - dose adjustment needed in renal insufficiency half life 6-9 hours
Dalbavancin - dose adjustment needed in renal insufficiency half life 346
Oritavancin - NO DOSE adjustment needed in renal insufficiency half life 245 hours

Question 9

Clinical use

Answer 9

use should only be considered in adults with infections due to resistant Gram-positive organisms where vancomycin, linezolid/tedizolid, AND daptomycin cannot be used

Question 10

Drug/Lab interactions

Answer 10

Telavancin and oritavancin interfere with coagulation tests (PT, INR, aPPT) by binding to artifical phospholipid surfaces
oritavancin is a weak inducer of CYP3A4 and a non-selective inhibitor of CYP2C9 and CYP2C19 - NO clinical significant drug interactions noted

Question 11

Black box warning with Televancin

Answer 11

Warning on use during pregnancy and perform pregnancy test in women before use

Question 12

Adverse effects

Answer 12

Televancin - Nephotoxicity (risk factors - renal insufficancy, older age, higher doses) , QTc prolongation, taste disturbances
All cause infusion related reactions, N/V/D,

Oritavancin and televancin are associated with red man syndrome

Question 13

True/False:Vancomycin is the drug of choice for infections due to MRSA.

Answer 13

TRUE

Question 14

Which antibiotic does NOT have activity against vancomycin-resistant Enterococcus faecalis (VRE)?
A. Quinupristin-dalfopristin
B. Linezolid
C. Daptomycin
D. Tedizolid
E. Oritavancin

Answer 14

A

Question 15

Which of the following antibiotic-adverse effect combinations is INCORRECT?

A.Daptomycin – myopathy
B.Synercid – nephrotoxicity
C.Linezolid – thrombocytopenia
D.Vancomycin – Red man syndrome
E.Telavancin – QTc prolongation

Answer 15

B