Lipopeptides

Question 1

Daptomycin intro

Answer 1

Developed in response to the need for antibiotics with activity against resistant gram positives (VRE, MRSA, VISA)

Question 2

Drug in class

Answer 2

Daptomycin

Question 3

MOA

Answer 3

Rapid Bactericidal
Daptomycin binds to bacterial membranes and inserts its lipophilic tail into the cell wall to form a transmembrane channel –> 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 4

Mechanism of resistance

Answer 4

Rarely reported in VRE and MRSA due to altered cell membrane binding

Question 5

Spectrum of activity

Answer 5

Gram positive bacteria:
Streptococcus pneumoniae (including PRSP)
Enterococcus faecium AND faecalis (including VRE – static)
Staphylococcus aureus and CNS (MSSA MRSA, VISA, VRSA, LRSA)

No activity with gram negative aerobes

Question 6

pharmacology

Answer 6

Concentration dependent
IV infusion

Question 7

Distribution

Answer 7

readily distributes into well perfused tissue
Does not penetrate CSf
90% protein bound - explains why it doesnt work in certain setting

Question 8

Elimination

Answer 8

Excreted primarily by the kidneys
Must dose adjust in renal insufficiency

Question 9

Clinical Use

Answer 9

• VRE where vancomycin and/or linezolid cannot be used
• Staphylococcus aureus bacteremia and endocarditis
• Daptomycin should NOT be used for the treatment of pneumonia since the compound is inactivated by pulmonary surfactant.

Question 10

Drug interactions

Answer 10

HMG-CoA reductase inhibitors(statins) - increase incidence of myopathy - use together with caution

Question 11

Adverse effects

Answer 11

Myopathy and CPK elevation - patient will complain of weakness and pain in muscles
Acute eosinophilic pneumonia
Gastrointestinal
Headache
Injection site reactions
Rash