Cubicin (daptomycin)

Comment

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.

 

History of Development of Cubicin

Clinical Trials

A retrospective review of clinical experience with daptomycin for a variety of wound types in a burn and wound care facility. South Med J. 2010 Aug; 103(8):748-52.

Overall success rates (microbiological cure and clnical improvement) of daptomycin for burn wounds was 98.5%, for complicated skin and soft tissue infection, chronic wounds, and other infections were 100%, and for wounds associated with bacteremia was 98%.

Efficacy and safety of daptomycin in the treatment of Gram-positive catheter-related bloodstream infections in cancer patients. Int J Antimicrob Agents 2010 Aug;36(2):182-6.

In cancer patients with Gram-positive catheter-related bloodstream infection, daptomycin recipients are more likely to achieve sympotms resolution and microbiological eradication at 48h than vancomycin recipients.

A Potential Role for Daptomycin in Enterococcal Infections: What is the Evidence? J Antimicrob Chemother. 2010 Jun;65(6):1126-36.

In recent years, large-scale susceptibility studies have shown that daptomycin is active against >98% of enterococci tested, irrespective of their susceptibility to other antibacterial agents. This lack of cross-resistance reflects the fact that daptomycin has a mode of action distinct from those of other antibiotics, including glycopeptides.

Use of Daptomycin in a Pregnant Patient with Staphylococcus aureus Endocarditis (April). Stroup JS, Wagner J, Badzinski T. Ann Pharmacothr. 2010 Mar 2.

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 Versus Other Antimicrobial Agents for the Treatment of Skin and Soft Tissue Infections: A Meta-Analysis(January). Bliziotis IA, Plessa E, Peppas G, Falagas ME. Ann Pharmacother. 2009 Nov 24. [Epub ahead of print]

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.

Safety of high-dose intravenous daptomycin treatment: three-year cumulative experience in a clinical program. Figueroa DA, Mangini E, Amodio-Groton M, Vardianos B, Melchert A, Fana C, Wehbeh W, Urban CM, Segal-Maurer S. Clin Infect Dis. 2009 Jul 15;49(2):177-80.

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.

Vancomycin-resistant enterococcal bacteraemia: is daptomycin as effective as linezolid? Mave V, Garcia-Diaz J, Islam T, Hasbun R. J Antimicrob Chemother. 2009 Jul;64(1):175-80.

This retrospective study showed comparable microbiological cure rates, relapse rates and mortality of vancomycin-resistant enterococcal bacteremia between linezolid and daptomycin.

Community-based outpatient parenteral antimicrobial therapy (CoPAT) for Staphylococcus aureus bacteraemia with or without infective endocarditis: analysis of the randomized trial comparing daptomycin with standard therapy. Rehm S, Campion M, Katz DE, Russo R, Boucher HW. J Antimicrob Chemother. 2009 May;63(5):1034-42.

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.

Daptomycin for the treatment of enterococcal bacteraemia: results from the Cubicin Outcomes Registry and Experience (CORE). Mohr JF, Friedrich LV, Yankelev S, Lamp KC. Int J Antimicrob Agents. 2009 Jun;33(6):543-8.

This study demonstrated that daptomycin as first- and second-line therapy successfully treated bloodstream infections caused by E. faecalis and E. faecium.

Daptomycin versus vancomycin plus gentamicin for treatment of bacteraemia and endocarditis due to Staphylococcus aureus: subset analysis of patients infected with methicillin-resistant isolates. Rehm SJ, Boucher H, Levine D, Campion M, Eisenstein BI, Vigliani GA, Corey GR, Abrutyn E. J Antimicrob Chemother. 2008 Dec;62(6):1413-21.

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

Therapeutic options for infections due to vancomycin-resistant enterococci. Wang JL, Hsueh PR. Expert Opin Pharmacother. 2009 Apr;10(5):785-96.

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.

Future directions with daptomycin. Livermore DM. J Antimicrob Chemother. 2008 Nov;62 Suppl 3:iii41-iii49.

The article summarized ongoing trials of daptomycin and compared daptomycin with other new anti-Gram-positive antibiotics.

Treatment of staphylococcal infections with cyclic lipopeptides. Eisenstein BI. Clin Microbiol Infect. 2008 Mar;14 Suppl 2:10-6.

This paper reviewed current clinical evidence of daptomycin as the therapeutic agent for the treatment of staphylococcal infections.

Adverse Drug Reactions and Warnings

FDA Information

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