Cyclic Lipopeotides

Question 1

Cyclic Lipopeptides

Answer 1

Daptomycin

Binds to cell membrane of Gram+ bacteria- cell wall weakens and allows essential ions to leak out- leads to rapid depolarization of membrane potential and cessation of needed cell processes- leads to cell death

Beta lactams blow bacteria apart
Dapto leaves dead bacteria intact

Question 2

Cyclic Lipopeptides MOA

Answer 2

Inserts into the cell membrane of Gram+ organisms; leakage of intracellular cations that maintain membrane polarization; results in rapid depolarization and cell death

Question 3

Cyclic Lipopeptides Spectrum

Answer 3

Good
MSSA / MRSA
Strep

Moderate to Good
Enterococci, including VRE

Poor
Anything Gram-

Question 4

Cyclic Lipopeptides Adverse Effects

Answer 4

Effects on skeletal muscle: muscle pain / weakness; even rhabdomyolysis
Monitor creatine kinase (CK) concentrations; check weekly
Toxicity can be decreased by administering no more than once daily; adjust interval in renal dysfunction

Eosinophilic pneumonia has been reported

Question 5

Cyclic Lipopeptides Important Facts

Answer 5

Active against many resistant Gram+ organisms (including VRE and MRSA)

Proven effective in staph endocarditis (especially right sided)- few abx have this indication

Resistance to Dapto is uncommon but reported
Have lab test isolate for susceptibility
Standard MIC for resistance has not need defined
Ask lab for specifics; may report as nonsusceptibile or report nothing if doesn’t fall in susceptible range

Don’t use for pneumonia; penetrates lung tissue well but human pulmonary surfactant makes it inactive by binding to Dapto

FDA approved dosing is 4-6mg/kg/day
Studies show higher doses (12mg) may be more effective without causing much more toxicity in difficult to treat infections

Studies show synergism between Dapto and some beta lactams (even in beta lactam resistant organisms like MRSA and VRE)

Remember: monitor CK and renal function (especially if on other drugs toxic to skeletal muscle like HMG-CoA reductase inhibitors

Question 6

Cyclic Lipopeptides Good For

Answer 6

Skin/ss infections caused by resistant Gram+ organisms and staph bacteremia (including right sided endocarditis)

Useful in enterococcal bacteremia (not indicated or well studied for this)