Lipoglycopeptides (Televancin, Dalbavancin)

Question 1

Introduction

Answer 1

Developed to address the need for antibiotics with activity against resistant Gram (+) bacteria

Question 2

MOA

Answer 2

Inhibits cell wall synthesis by binding to D-ala-D-ala cell wall precursors AND causes membrane depolarization by inserting lipophilic tail in cell wall

Bactericidal–>Concentration dependent

Question 3

MOR

Answer 3

Modification of the D-ala-D-ala vancomycin binding site

Question 4

Spectrum of activity

Answer 4

Gram (+) aerobes–> excellent activity
- Enterococcus faecium and faecalis–> some strains of VRE display resistance to televancin and dalbavancin
- MSSA, MRSA, VISA; Ortiavancin also displays activity against VRSA

Question 5

Distribution

Answer 5

All agents distribute fairly well into tissues

Poor penetration into CSF

Question 6

Elimination

Answer 6

Televancin–> kidneys
- Dose adjustments in renal insufficiency

Dalbavancin–> feces and urine
- t1/2= 346 hours
- Dose adjustments in renal insufficiency who are not receiving HD

Oritavancin–> ??
- t1/2= 245 hours
- No dose adjustments in renal or hepatic insufficiency

Question 7

Clinical uses

Answer 7

Should only be considered in adults with infections due to resistance Gram (+) organisms where Vancomycin, daptomycin, linezolid/tedizolid cannot be used

Question 8

Drug/lab interactions

Answer 8

Televancin and Oritavancin interfere with results of coagulation tests (PT, INR, PTT)

Dalbavancin is a weak induce of CYP3A4, non-selective inhibitor of CYP2C9 and CYP2C19–> no interactions noted

Question 9

Adverse effects

Answer 9

Red Man Syndrome–> ALL

Nephrotoxicity–>Televancin
- Higher in pts with renal dysfunction, preexisting renal disease, heart failure, diabetes, HTN, receiving other nephrotoxins, > 65 years of age

QTc prolongation–> Televancin

Taste disturbances

Question 10

Use in pregnancy

Answer 10

Televancin is Pregnancy Category C

BBW for use in pregnancy: pregnancy test before use