Cyclic Lipopeptides

Agent: daptomycin

Daptomycin is the only cyclic lipopeptide that has made its way onto the market. It has a unique mechanism of action and target compared with other antibiotics. Daptomycin binds to the cell membrane of Gram-positive bacteria, weakening it and allowing essential ions to leak out of the organ-ism. This leads to a rapid depolarization of the membrane potential and cessation of needed cell processes, leading to cell death. Interestingly, in-stead of blowing the bacteria apart as beta-lactams do, daptomycin leaves the dead bacteria intact.

Spectrum

Good: MSSA, MRSA, streptococci

Moderate to Good: enterococci, including VRE

Poor : anything Gram-negative

Adverse Effects

Daptomycin has effects on skeletal muscle that can manifest as muscle pain or weakness, or possibly rhabdomyolysis. To monitor for this effect, creatine kinase (CK) concentrations should be checked weekly while on therapy. This toxicity can be de-creased by administering the drug no more than once daily and by adjusting the interval in renal dysfunction. Drug fever is also a possibility. Recently, eosinophilic pneumonia has been reported in patients on daptomycin therapy.

Important Facts

• Daptomycin is active against many resistant Gram-positive organisms, including VRE and MRSA. It has been proven effective in staphylococcal endocarditis (specifically right-sided endocarditis), an indication that few antibiotics have.

• Resistance to daptomycin is very rare, but it is reported occasionally. Before using daptomycin for your patient, ensure that the lab tests the isolate for daptomycin susceptibility. Because a standard MIC for resistance has not yet been defined, labs may report isolates as “nonsusceptible” or, worse, not report them at all if they do not fall into the susceptible range. Ask your lab for specifics on its procedures.

• Though it penetrates lung tissue very well,   daptomycin cannot be used to treat pneumonia.  Human pulmonary surfactant binds to daptomycin, rendering it inactive. Early clinical trials showed poor outcomes in daptomycin-treated pneumonia patients.

What It’s Good For

Skin and soft-tissue infections caused by resistant Gram-positive organisms and staphylococcal bacteremia, including right-sided endocarditis. Daptomycin also has utility in enterococcal bacteremia,  though it is not indicated or as well studied for this use.

Don’t Forget!

Monitor CK concentrations and renal function for patients taking daptomycin, particularly if they are on other drugs toxic to skeletal muscle, like HMG-CoA reductase inhibitors.

References

Gallagher ,J.C. and MacDougall ,c. (2012). Antibiotics Simplified. Second Edition. Jones & Bartlett Learning, LLC.