Daptomycin Flashcards
Daptomycin is a (structure)
13 membered amino acid cyclic lipopeptide compound
Daptomycin has a _____core and ____ tail
water soluble hydrophilic; lipophilic
Daptomycin is bactericidal/bacteriostatic
bactericidal but does not rupture the cell
Daptomycin MOA
- lipophilic portion of compound binds and inserts itself into the cytoplasmic membrane in a calcium dependent manner
- disruption of the cell membrane
- 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
Daptomycin has less/more immune response and why
less because there is no sudden release of exotoxin proteins since the cell does not lyse
Daptomycin spectrum coverage
GRAM + ONLY
dark purple: streptococcus, s. pneumoniae, viridans, MSSA, MRSA, e. faecalis, e. faecium, VRE
Daptomycin oral absorption
poor IV only
Daptomycin 1/2 life
8-9 hours- long!!
Daptomycin elimination
78% renal and 50% unchanged in urine
Daptomycin PK/PD parameters
Cmax: MIC or AUC: MIC
Daptomycin dosing has to be adjusted for
body weight
Daptomycin dosing is usually
every 24 or 48 hours
Daptomycin dose for e. faecium
8-12mg/kg
Daptomycin adverse effects
myopathy and rhabdomyolysis
reversible
increased creatinine phosphokinase CPK
muscle pain or weakness (distal extremities)
How to monitor CPK levels with Daptomycin
at baseline and weekly
Discontinue Daptomycin if:
myopathy in conjunction with CPK > 1000 U/L
OR
asymptomatic with marked elevation in CPK with levels > 2000 U/L
Rare adverse effect that happens with Daptomycin
eosinophilic pneumonia
when eosinophils accumulate in the lungs
When does eosinophilic pneumonia occur after Daptomycin?
2-4 weeks after starting
How does eosinophilic pneumonia get treated?
goes away after discontinuing daptomycin and steroid therapy
Eosinophilic pneumonia should be suspected in presence of
fever, hypoxia, pulmonary infiltrates
Daptomycin drug interactions
No
Daptomycin resistnace
- 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
Daptomycin has synergy with
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
Daptomycin indications
skin and soft tissue infections
bacteremia
endocarditis
osteomyelitis
Daptomycin limitations of use
cannot be used for treatment of pneumonia because it is inactivated by the pulmonary surfactant
Daptomycin CNS penetration
poor
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
c
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
c
