Mechanism of Action

With a unique mechanism of action, CUBICIN kills bacteria without cytoplasm penetration and lysis1-3

Only CUBICIN (daptomycin):

  • Irreversibly binds to the cytoplasmic cell membrane of Gram-positive bacteria1-3
    • – Calcium-dependent insertion of molecule into membrane
    • – Oligomerization to form a pore or ion channel (hypothetical)
  • Rapidly depolarizes the cell membrane3


Indications: CUBICIN® (daptomycin) is indicated for the treatment of complicated skin and skin structure infections (cSSSI) caused by susceptible isolates of the following Gram-positive bacteria: Staphylococcus aureus (including methicillin-resistant isolates), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus dysgalactiae subspecies equisimilis, and Enterococcus faecalis (vancomycin-susceptible isolates only); and S. aureus bloodstream infections (bacteremia), including patients with right-sided infective endocarditis.

Limitations of Use: CUBICIN is not indicated for the treatment of left-sided infective endocarditis (LIE) due to S. aureus. CUBICIN has not been studied in patients with prosthetic valve endocarditis. CUBICIN is not indicated for the treatment of pneumonia.

Warnings and Precautions

  • Anaphylaxis/hypersensitivity reactions, which may be life-threatening, have been reported with CUBICIN use. If an allergic reaction occurs, discontinue CUBICIN and treat appropriately.
  • Myopathy and rhabdomyolysis have been reported with CUBICIN use. Monitor for muscle pain or weakness, particularly
 of the distal extremities. Monitor creatine phosphokinase (CPK) levels weekly and more frequently in patients with CPK elevations while on CUBICIN treatment and in those who received recent prior or concomitant HMG-CoA reductase inhibitors. In patients with renal impairment, monitor renal function and CPK levels more than once weekly. Discontinue CUBICIN in patients with unexplained signs and symptoms of myopathy with CPK levels >1,000 U/L (~5× ULN), and in patients without symptoms and CPK levels >2,000 U/L (≥10× ULN). In addition, consider temporarily suspending agents associated with rhabdomyolysis, such as HMG-CoA reductase inhibitors.
  • Eosinophilic pneumonia has been reported with CUBICIN use. Promptly evaluate patients who develop fever, dyspnea with hypoxic respiratory insufficiency, and diffuse pulmonary infiltrates and discontinue CUBICIN immediately. Treatment with systemic steroids is recommended. Recurrence of eosinophilic pneumonia upon re-exposure has been reported.
  • Peripheral neuropathy has been reported with CUBICIN use. Monitor for signs and symptoms of peripheral neuropathy.
  • Potential nervous and/or muscular system effects in patients younger than 12 months: Avoid use of CUBICIN in patients younger than 12 months due to the risk of potential effects on muscular, neuromuscular, and/or nervous systems (either peripheral and/or central) observed in neonatal dogs.
  • Clostridium difficile–associated diarrhea (CDAD), ranging from mild diarrhea to fatal colitis, has been reported with nearly all systemic antibacterial agents, including CUBICIN. Careful medical history is necessary because CDAD has been reported to occur more than two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, antibacterial use not directed against C. difficile should be discontinued, if possible.
  • Patients with persisting or relapsing S. aureus bacteremia/endocarditis, possibly due to reduced daptomycin susceptibility, or poor clinical response should have repeat blood cultures. Appropriate surgical intervention and/or change in antibacterial regimen may be required. Failure of treatment due to persisting or relapsing S. aureus bacteremia/endocarditis may be due to reduced daptomycin susceptibility.
  • In the cSSSI and S. aureus bacteremia/endocarditis trials, decreased efficacy was observed in CUBICIN-treated patients with moderate baseline renal impairment (CrCL <50 mL/min).

Adverse Reactions: The most clinically significant adverse reactions observed with CUBICIN 4 mg/kg (cSSSI trials) and 6 mg/kg (S. aureus bacteremia/endocarditis trial) were abnormal liver function tests, elevated CPK, and dyspnea.

Please see full Prescribing Information.


  1. Canepari P, Boaretti M, Lleó MM, et al. Lipoteichoic acid as a new target for activity of antibiotics: mode of action of daptomycin (LY146032). Antimicrob Agents Chemother. 1990;34(6):1220-1226.
  2. Cotroneo N, Harris R, Perlmutter N, et al. Daptomycin exerts bactericidal activity without lysis of Staphylococcus aureus. Antimicrob Agents Chemother. 2008;52(6):2223-2225.
  3. Steenbergen JN, Alder J, Thorne GM, et al. Daptomycin: a lipopeptide antibiotic for the treatment of serious Gram-positive infections. J Antimicrob Chemother. 2005;55(3):283-288.