Lipopeptides (Daptomycin)

Question 1

Daptomycin MOA

Answer 1

Binds to bacterial membranes and inserts lipophilic tail which leads to membrane depolarization

Rapid bactericidal activity–> concentration-dependent

Question 2

MOR

Answer 2

Resistance has been rarely reported in VRE and MRSA due to altered cell membrane binding through loss of protein

Question 3

Spectrum of activity

Answer 3

Gram (+) aerobes–> excellent activity
- PRSP
- Enterococcus faecium AND faecalis including VRE
- MSSA, MRSA, VISA, VRSA, LRSA

Gram (-)–> INACTIVE

Question 4

Distribution

Answer 4

Distributes fairly well into tissues and is highly protein bound to albumin

Does not penetrate CSF

Question 5

Elimination

Answer 5

Excreted primarily by the kidneys

Dose adjustments are required in renal insufficiency

Question 6

Clinical uses and dosing

Answer 6

Inexpensive

Reserved for treatment of serious/complication infections caused by resistant Gram (+) bacteria where Vancomycin and/or Linezolid cannot be used

Staphylococcus aureus bacteremia and endocarditis

VRE

Question 7

Pearls

Answer 7

Daptomycin should be not used for the treatment of pneumonia since the compound is inactivated by pulmonary surfactant

Question 8

Drug interactions

Answer 8

HMG-CoA reductase inhibitors (statins)–> increased myopathy

Question 9

Adverse effects

Answer 9

GI–> N/D
Headache
Injection site reactions
Rash
Myopathy and CPK elevation
Acute eosinophilic pneumonia