Cubicin (daptomycin)
Clinical Studies Review Articles Adverse Effects FDA Information Manufacturer
Commentary
Daptomycin is the first of a new class of antibiotics, the cyclic lipopeptides. It exerts bactericidal action via depolarization of the cell membrane in a rapid (<1 hour) and concentration-dependent manner with a post-antibiotic effect. It possesses broad activity against Gram-positive pathogens, such as Streptococcus, Staphylococcus (including methicillin-resistant isolates), and Enterococcus faecalis/E. faecium (including vancomycin-resistant isolates).
Daptomycin is currently approved by FDA for the treatment of 1) complicated skin and skin structure infections (4 mg/kg/day) caused by S. aureus (including methicillin-resistant isolates), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus dysgalactiaesubspecies equisimilis, and Enterococcus faecalis (vancomycin-susceptible isolates only), and 2) S. aureus bacteremia (6 mg/kg/day), including those with right-sided infective endocarditis, caused by methicillin-susceptible and methicillin-resistant isolates. Because daptomycin is inactivated by surfactant in the lung, so it should not be used for the treatment of respiratory infections.
Daptomycin has no interaction with P450 cytochrome. It is mainly excreted unchanged in the urine, and the dosing interval should be increased from 24 h to 48 h in patients with a creatinine clearance below 30 ml/min. The specific adverse drug reaction of daptomycin is its reversible elevation of creatinine phosphokinase (CPK) isoenzymes released by the skeletal muscle. At 4 mg/kg/day, the reported incidence of CPK elevation was 2.5% and myopathy 0.2%. Weekly CPK level monitoring is recommended in patients receiving daptomycin.
Clinical Studies
Daptomycin at the dose of 6 mg/kg for 6 weeks has effectively and safely cured Staphylocuccus aureus endocarditis in a pregnant woman in the second trimester.
Daptomycin is as effective and safe as vancomycin and semisynthetic penicillins for the treatment of SSTIs while fewer patients with complicated SSTI receiving daptomycin required prolonged treatment and had faster clinical cure in 2 of the 4 analyzed studies.
Daptomycin demonstrated concentration-dependent killing in vitro, and this study presented the safety of daptomycin at a mean dose of 8 mg/kg for a median duration of 25 days.
This retrospective study showed comparable microbiological cure rates, relapse rates and mortality of vancomycin-resistant enterococcal bacteremia between linezolid and daptomycin.
Once daily dosing of daptomycin is an attractive choice in the community setting, and this study provided the evidence for the outpatient daptomycin use in patients with S. aureus bacteremia and infective endocarditis.
This study demonstrated that daptomycin as first- and second-line therapy successfully treated bloodstream infections caused by E. faecalis and E. faecium.
Compared with vancomycin/gentamicin, daptomycin performed comparably well as the therapeutic agent for patients with MRSA bacteremia and right-sided endocarditis (success rates 44.4% vs. 32.6%, p>0.05).
Review Articles
This paper extensively reviewed recent in vitro antimicrobial susceptibility of vancomycin-resistant enterococci (VRE) and clinical trials/case series of new antibiotic treatments for infection due to VRE, and suggested daptomycin and tigecycline have promising role in treatment of VRE infection.
The article summarized ongoing trials of daptomycin and compared daptomycin with other new anti-Gram-positive antibiotics.
This paper reviewed current clinical evidence of daptomycin as the therapeutic agent for the treatment of staphylococcal infections.
Adverse Drug Reactions and Warnings
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