Daptomycin

Question 1

Daptomycin is a (structure)

Answer 1

13 membered amino acid cyclic lipopeptide compound

Question 2

Daptomycin has a _____core and ____ tail

Answer 2

water soluble hydrophilic; lipophilic

Question 3

Daptomycin is bactericidal/bacteriostatic

Answer 3

bactericidal but does not rupture the cell

Question 4

Daptomycin MOA

Answer 4

1. lipophilic portion of compound binds and inserts itself into the cytoplasmic membrane in a calcium dependent manner
2. disruption of the cell membrane
3. formation of channel that causes depolarization of the membrane
   ion-conducting structures that allow efflux of potassium ions
   release of intracellular ions causes protein synthesis to seize and results in cell death

Question 5

Daptomycin has less/more immune response and why

Answer 5

less because there is no sudden release of exotoxin proteins since the cell does not lyse

Question 6

Daptomycin spectrum coverage

Answer 6

GRAM + ONLY

dark purple: streptococcus, s. pneumoniae, viridans, MSSA, MRSA, e. faecalis, e. faecium, VRE

Question 7

Daptomycin oral absorption

Answer 7

poor IV only

Question 8

Daptomycin 1/2 life

Answer 8

8-9 hours- long!!

Question 9

Daptomycin elimination

Answer 9

78% renal and 50% unchanged in urine

Question 10

Daptomycin PK/PD parameters

Answer 10

Cmax: MIC or AUC: MIC

Question 11

Daptomycin dosing has to be adjusted for

Answer 11

body weight

Question 12

Daptomycin dosing is usually

Answer 12

every 24 or 48 hours

Question 13

Daptomycin dose for e. faecium

Answer 13

8-12mg/kg

Question 14

Daptomycin adverse effects

Answer 14

myopathy and rhabdomyolysis
reversible
increased creatinine phosphokinase CPK
muscle pain or weakness (distal extremities)

Question 15

How to monitor CPK levels with Daptomycin

Answer 15

at baseline and weekly

Question 16

Discontinue Daptomycin if:

Answer 16

myopathy in conjunction with CPK > 1000 U/L
OR
asymptomatic with marked elevation in CPK with levels > 2000 U/L

Question 17

Rare adverse effect that happens with Daptomycin

Answer 17

eosinophilic pneumonia

when eosinophils accumulate in the lungs

Question 18

When does eosinophilic pneumonia occur after Daptomycin?

Answer 18

2-4 weeks after starting

Question 19

How does eosinophilic pneumonia get treated?

Answer 19

goes away after discontinuing daptomycin and steroid therapy

Question 20

Eosinophilic pneumonia should be suspected in presence of

Answer 20

fever, hypoxia, pulmonary infiltrates

Question 21

Daptomycin drug interactions

Answer 21

No

Question 22

Daptomycin resistnace

Answer 22

• diversion with enterococcus faecalis only. this occurs when redistribution of anionic phospholipid microdomains occurs away from the septal plane, resulting in ineffective binding of the drug
• repulsion only in s. aureus and e. faecium. this is caused by electrostatic repulsion of the positively charged daptomycin-calium complex from the cell membrane in a process associated with increase in net positive charge of the cell envelope

Question 23

Daptomycin has synergy with

Answer 23

beta-lactams
exposure to beta-lactams increases the negative charge of the cell surface leading to an increase in daptomycin binding and improved bactericidal activity

Question 24

Daptomycin indications

Answer 24

skin and soft tissue infections
bacteremia
endocarditis
osteomyelitis

Question 25

Daptomycin limitations of use

Answer 25

cannot be used for treatment of pneumonia because it is inactivated by the pulmonary surfactant

Question 26

Daptomycin CNS penetration

Answer 26

poor

Question 27

Which of the following lab values should be assessed during Daptomycin therapy?

a. urine creatinine, creatinine phosphokinase
b. white blood cell count, lactate
c. serum creatinine, creatinine phosphokinase
d. serum potassium, serum calcium

Answer 27

c

Question 28

Which of the following results in increased daptomycin resistance among s. aureus isolates?

a. presence of mega gene
b. ESBL production
c. increase in net-positive cell surface charge
d. alterations in ribosomal targets

Answer 28

c