Mechanism of Action

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

Only CUBICIN (daptomycin for injection):

  • 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



  • CUBICIN® (daptomycin for injection) is indicated for the following infections:
    • 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).
    • S. aureus bloodstream infections (bacteremia), including those with right-sided infective endocarditis, caused by methicillin-susceptible and methicillin-resistant isolates.


  • CUBICIN is not indicated for the treatment of left-sided infective endocarditis due to S. aureus. The clinical trial of CUBICIN in patients with S. aureus bloodstream infections included limited data from patients with left-sided infective endocarditis; outcomes in these patients were poor. CUBICIN has not been studied in patients with prosthetic valve endocarditis.
  • CUBICIN is not indicated for the treatment of pneumonia.


  • Anaphylaxis/hypersensitivity reactions have been reported with the use of antibacterial agents, including CUBICIN, and may be life-threatening. If an allergic reaction to CUBICIN occurs, discontinue the drug and institute appropriate therapy.
  • Myopathy, defined as muscle aching or muscle weakness in conjunction with increases in creatine phosphokinase (CPK) values to greater than 10 times the upper limit of normal (ULN), has been reported with the use of CUBICIN. Rhabdomyolysis, with or without acute renal failure, has been reported. Patients receiving CUBICIN should be monitored for the development of muscle pain or weakness, particularly of the distal extremities. In patients who receive CUBICIN, CPK levels should be monitored weekly, and more frequently in patients who received recent prior or concomitant therapy with an HMG-CoA reductase inhibitor or in whom elevations in CPK occur during treatment with CUBICIN. In patients with renal impairment, both renal function and CPK should be monitored more frequently than once weekly. In Phase 1 studies and Phase 2 clinical trials, CPK elevations appeared to be more frequent when CUBICIN was dosed more than once daily. Therefore, CUBICIN should not be dosed more frequently than once a day. CUBICIN should be discontinued in patients with unexplained signs and symptoms of myopathy in conjunction with CPK elevations to levels >1,000 U/L (~5× ULN), and in patients without reported symptoms who have marked elevations in CPK, with levels >2,000 U/L (≥10× ULN). In addition, consideration should be given to suspending agents associated with rhabdomyolysis, such as HMG-CoA reductase inhibitors, temporarily in patients receiving CUBICIN.
  • Eosinophilic pneumonia has been reported in patients receiving CUBICIN. In reported cases associated with CUBICIN, patients developed fever, dyspnea with hypoxic respiratory insufficiency, and diffuse pulmonary infiltrates. In general, patients developed eosinophilic pneumonia 2 to 4 weeks after starting CUBICIN and improved when CUBICIN was discontinued and steroid therapy was initiated. Recurrence of eosinophilic pneumonia upon re-exposure has been reported. Patients who develop these signs and symptoms while receiving CUBICIN should undergo prompt medical evaluation, and CUBICIN should be discontinued immediately. Treatment with systemic steroids is recommended.
  • Cases of peripheral neuropathy have been reported during the CUBICIN postmarketing experience. Therefore, physicians should be alert to signs and symptoms of peripheral neuropathy in patients receiving CUBICIN.
  • Clostridium difficile–associated diarrhea (CDAD) has been reported with the use of nearly all systemic antibacterial agents, including CUBICIN, and may range in severity from mild diarrhea to fatal colitis. CDAD must be considered in all patients who present with diarrhea following antibacterial use. Careful medical history is necessary because CDAD has been reported to occur more than 2 months after the administration of antibacterial agents.
  • Patients with persisting or relapsing S. aureus bacteremia/endocarditis or poor clinical response should have repeat blood cultures. If a blood culture is positive for S. aureus, minimum inhibitory concentration (MIC) susceptibility testing of the isolate should be performed using a standardized procedure, and diagnostic evaluation of the patient should be performed to rule out sequestered foci of infection. Appropriate surgical intervention (e.g., debridement, removal of prosthetic devices, valve replacement surgery) and/or consideration of a 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 (as evidenced by increasing MIC of the S. aureus isolate).
  • There are limited data available from the cSSSI clinical trials regarding the clinical efficacy of CUBICIN treatment in patients with creatinine clearance (CrCL) <50 mL/min; only 6% (31/534) patients treated with CUBICIN in the intent-to-treat (ITT) population had a baseline CrCL <50 mL/min. The clinical success rates in CUBICIN (4 mg/kg q24h)-treated patients with CrCL 50–70 mL/min and CrCL 30–<50 mL/min were 66% (25/38) and 47% (7/15), respectively. The clinical success rates in comparator-treated patients with CrCL 50–70 mL/min and CrCL 30–<50 mL/min were 63% (30/48) and 57% (20/35), respectively. In a subgroup analysis of the ITT population in the S. aureus bacteremia/endocarditis trial, clinical success rates in the CUBICIN-treated patients were lower in patients with baseline CrCL <50 mL/min.


  • 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.

HMG-CoA=3-hydroxy-3-methylglutaryl-coenzyme A.


  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.