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
- 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.
- Success rates for pathogen-specific therapy at 6-week Test of Cure in MRSA and MSSA patients (mITT population).
- 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.
- 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).
- 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)|
- 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.
- 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