CUBICIN® (daptomycin for injection) was proven to be noninferior to comparators for treatment of S. aureus bacteremia in adults1

Clinical success in the pivotal CUBICIN S. aureus bacteremia and endocarditis study1,a

Clinical success in the pivotal CUBICIN S. aureus bacteremia and endocarditis study

  1. In an open-label, randomized trial of CUBICIN® (daptomycin for injection) vs standard therapy in the treatment of S. aureus bacteremia, adult patients who received CUBICIN were compared with adult patients who received vancomycin or an antistaphylococcal penicillin (nafcillin, oxacillin, or flucloxacillin) for a duration of therapy determined by investigators based on the working diagnosis. The primary endpoint of the study was defined as clinical success rate at the visit 42 days after the end of therapy.
  2. Success rates for pathogen-specific therapy at 6-week Test of Cure in MRSA and MSSA patients (mITT population).
  3. Patients in the MRSA subgroup of the comparator treatment arm were to receive vancomycin (1 g q12h) + 4 days of initial low-dose gentamicin (1 mg/kg q8h); however, one patient received a semisynthetic penicillin (2 g q4h) instead of vancomycin + 4 days of initial low-dose gentamicin and 4 patients received vancomycin alone. Patients in the MSSA subgroup of the comparator treatment arm were to receive a semisynthetic penicillin (2 g q4h) + 4 days of initial low-dose gentamicin (1 mg/kg q8h); however, 10 patients received vancomycin instead of semisynthetic penicillin and 3 patients received semisynthetic penicillin alone.
  4. Noninferiority was observed in both the MRSA (97.5% CI: -10.2, 35.5) and MSSA (97.5% CI: -22.6, 14.6) groups, as well as Overall (95% CI: -10.2, 15.1).
  5. The MRSA subgroup was prespecified in the protocol.
  • The efficacy of CUBICIN in patients with left-sided infective endocarditis due to S. aureus has not been demonstrated. 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
  • During the trial, 18/120 patients in the CUBICIN arm and 19/116 patients in the comparator arm died. These included 3/28 CUBICIN-treated patients and 8/26 comparator-treated patients with endocarditis
  • Failure of treatment due to persisting or relapsing S. aureus infections was seen in 16% (19/120) of CUBICIN-treated patients and 10% (11/115) of comparator-treated patients1

Patients in the S. aureus bacteremia and endocarditis trial were seriously ill and balanced between treatment groups1

Baseline Characteristics CUBICIN, n (%) Comparator Therapy, n (%)
Diabetes mellitus 44 (36.7) 42 (36.5)
Systemic inflammatory response syndrome 89 (74.2) 87 (75.7)
Injection-drug use 25 (20.8) 25 (21.7)
Preexisting valvular heart disease 16 (13.3) 9 (7.8)
Surgery within previous 30 days 49 (40.8) 36 (31.3)
Extravascular foreign materiala 28 (23.3) 29 (25.2)
Septic pulmonary emboli 10 (8.3) 13 (11.3)
HIV-positiveb 8 (6.7) 1 (0.9)
Median age 50.5 55
  1. Extravascular foreign material included orthopedic prostheses in 18 patients who received daptomycin and 12 patients who received comparator therapy, neurologic devices in 1 patient who received daptomycin, and other extravascular foreign material (sternal wires; surgical drains, clamps, and stents; nonvascular catheters; and chest and endotracheal tubes) in 11 patients who received daptomycin and 22 patients who received comparator therapy. More than 1 type of extravascular foreign material could be present in each patient. Orthopedic prostheses were infected in 8 patients (6 who received daptomycin and 2 who received comparator therapy), 6 of whom underwent surgical therapy, and 2 of the 6 (both treated with daptomycin) had a successful outcome.
  2. P=0.04 for the comparison between groups.

CUBICIN® (daptomycin for injection) is included in the IDSA guidelines as an option for initial therapy of MRSA bacteremia (AI)2

The strength of recommendation and quality of evidence of CUBICIN as an option for initial therapy of MRSA bacteremia are as follows:

  • Strength of recommendation “A” defined as good evidence to support recommendation for or against use
  • Quality of evidence “I” defined as evidence from ≥1 properly randomized, controlled trials

Learn about the adverse reaction profile of CUBICIN in adult patients with bacteremia. »

Learn about the efficacy of CUBICIN in adult patients with cSSSI. »

Indications and Usage

 
 

Learn about the adverse reaction profile of CUBICIN in adult patients with bacteremia. »

Learn about the efficacy of CUBICIN in adult patients with cSSSI. »

CI=confidence interval; CrCL=creatinine clearance; HMG-CoA=3-hydroxy-3-methylglutaryl-coenzyme A; IDSA=Infectious Diseases Society of America; mITT=modified intent to treat; MRSA=methicillin-resistant S. aureus; MSSA=methicillin-susceptible S. aureus; ULN=upper limit of normal.

References: 1. Fowler VG Jr, Boucher HW, Corey GR, et al; S. aureus Endocarditis and Bacteremia Study Group. Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus. N Engl J Med. 2006;355(7):653-665. 2. Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;52(3):e18-e55.


Indications: CUBICIN and CUBICIN RF are indicated for the treatment of adult and pediatric patients (1 to 17 years of age) with 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).

CUBICIN and CUBICIN RF are indicated for the treatment of adult patients with Staphylococcus aureus bloodstream infections (bacteremia), including those with right-sided infective endocarditis, caused by methicillin-susceptible and methicillin-resistant isolates.

CUBICIN and CUBICIN RF are indicated for the treatment of pediatric patients (1 to 17 years of age) with Staphylococcus aureus bloodstream infections (bacteremia).

Limitations of Use: CUBICIN and CUBICIN RF are not indicated for the treatment of pneumonia. CUBICIN and CUBICIN RF are not indicated for the treatment of left-sided infective endocarditis (LIE) due to S. aureus. CUBICIN and CUBICIN RF have not been studied in patients with prosthetic valve endocarditis. CUBICIN and CUBICIN RF are not recommended in pediatric patients younger than 1 year of age due to the risk of potential effects on muscular, neuromuscular, and/or nervous systems (either peripheral and/or central) observed in neonatal dogs.

Usage: To reduce the development of drug-resistant bacteria and maintain the effectiveness of CUBICIN and CUBICIN RF and other antibacterial drugs, CUBICIN and CUBICIN RF should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information is available, it should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. Empiric therapy may be initiated while awaiting test results.

Selected Important Safety Information

  • Anaphylaxis/hypersensitivity reactions, which may be life-threatening, have been reported with CUBICIN use. If an allergic reaction occurs, discontinue CUBICIN or CUBICIN RF 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 or CUBICIN RF 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 or CUBICIN RF 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 or organizing pneumonia and discontinue CUBICIN or CUBICIN RF 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 and consider discontinuation.
  • Potential nervous and/or muscular system effects in patients younger than 12 months: Avoid use of CUBICIN and CUBICIN RF 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. Evaluate all patients who present with diarrhea following antibacterial use. 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 adult patients with moderate baseline renal impairment (CrCL <50 mL/min).
  • Adverse Reactions:

    Adult cSSSI Patients: The common adverse reactions that occurred in ≥2% of adult cSSSI patients receiving CUBICIN 4 mg/kg were diarrhea (5.2%), headache (5.4%), dizziness (2.2%), rash (4.3%), abnormal liver function tests (3.0%), elevated creatinine phosphokinase (CPK) (2.8%), urinary tract infections (2.4%), hypotension (2.4%), and dyspnea (2.1%).

    Adult S. aureus bacteremia/endocarditis Patients: The most common adverse reactions that occurred in ≥5% of S. aureus bacteremia/endocarditis patients receiving CUBICIN 6 mg/kg were sepsis (5%), bacteremia (5%), abdominal pain (6%), chest pain (7%), edema (7%), pharyngolaryngeal pain (8%), pruritus (6%), increased sweating (5%), insomnia (9%), elevated CPK (7%), and hypertension (6%).

    Pediatric cSSSI Patients: The most common adverse reactions that occurred in ≥2% of pediatric patients receiving CUBICIN were diarrhea (7.0%), vomiting (2.7%), abdominal pain (2.0%), pruritus (3.1%), pyrexia (3.9%), elevated CPK (5.5%), and headache (2.7%).

    Pediatric S. aureus bacteremia Patients: The most common adverse reactions that occurred in ≥5% of pediatric patients receiving CUBICIN were vomiting (10.9%) and elevated CPK (7.3%).

Before prescribing CUBICIN® (daptomycin for injection), please read the accompanying Prescribing Information.

Before prescribing CUBICIN® RF (daptomycin for injection), please read the accompanying Prescribing Information.



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Selected Important Safety Information
Anaphylaxis/hypersensitivity reactions, which may be life-threatening, have been reported with CUBICIN use. If an allergic reaction occurs, discontinue CUBICIN or CUBICIN RF and treat appropriately.