Pharmacology Update: Daptomycin Injection (Cubicin)
Daptomycin Injection (Cubicin)
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD
The FDA has approved the first of a new class of antibiotics for the treatment of complicated skin and skin structure infections. Daptomycin is a cyclic lipopeptide that is active against Gram-positive bacteria. Daptomycin injection is manufactured by Abbott Laboratories and marketed by Cubist Pharmaceutical Inc as Cubicin.
Indications
Daptomycin is indicated for the treatment of complicated skin and skin structure infections caused by susceptible strains of Staphylococcus aureus (including methicillin-resistant strain), Streptococcus pyogenes, S agalactiae, S dysgalactiae subsp equisimilis, and Enterococcus faecalis (vancomycin-susceptible strains only).1
Dosage
The dose of daptomycin is 4 mg/kg given by intravenous infusion for a 30-minute period once every 24 hours for 7-14 days. The dose should be reduced to 4 mg/kg every 48 hours if the patient’s creatinine clearance is < 30 mL/min including patients on peritoneal or hemodialysis.1
Potential Advantages
Daptomycin has shown potent in vitro activity against S aureus and enterococci including resistant strains such as glycopeptide-resistant enterococci and methicillin-resistant S aureus.1,2 In one in vitro study, daptomycin showed greater bactericidal activity than linezolid, quinupristin-dalfopristin, and vancomycin against methicillin-resistant S aureus and Staphylococcus epidermidis, vancomycin-resistant enterococci, and vancomycin-intermediate S aureus.3 Cross-resistance to other classes of antimicrobials have not been identified. Daptomycin is dosed once daily.
Potential Disadvantages
Patients should be monitored for the development of muscle pain or weakness. In clinical studies about 3% of patients had elevated CK levels.1 Most common side effects include gastrointestinal disorders (eg, constipation, nausea), injection site reactions, fever, headache, dizziness, and rash.1 Daptomycin is not available in an oral dosage form. Daptomycin is not approved for pneumonia and appeared to be less effective than ceftriaxone for the treatment of pneumonia.4
Comments
Daptomycin is the first of a new class of antimicrobial agents, the cyclic lipopeptids, that are believed to act by causing depolarization of the bacterial membrane potentially leading to cell death.1 It has been studied in 2, unpublished, randomized, multinational studies in adults with complicated skin and skin structure infections. In these studies, which were conducted primarily in non-US sites, 554 patients were treated with daptomycin and 558 patients were treated with a comparator. Comparators were vancomycin or a semisynthetic penicillinase-resistant penicillin (eg, cloxacillin, nafcillin).1 Overall, treatment success, whether assessed on an intent-to-treat (ITT) basis or in clinical evaluable (CE) population, were comparable. Success based on ITT and CE were 62.5% and 80.4% for the 2 studies, respectively, compared to 60.9% and 80.5% for the comparators. The majority of the pathogens isolated for each study arm were methicillin-susceptible S aureus (196 for daptomycin, 207 for comparators) followed by S pyogens (84-88) and E facaelis (37-53). More than 50% of the infections were wound infections or major abscess. Daptomycin appears to be well tolerated with side effects that are not dramatically different than the comparator except for CK elevations. The wholesale cost for daptomycin is about $11 for 4 mg. A 10-day cost for a 70 kg patient is about $7500.
Clinical Implications
Finding antimicrobial agents that are active against resistant Gram-positive pathogens is a continuing challenge. The most common of these pathogens are methicillin-resistant S aureus and vancomycin-resistant enterococci. Daptomycin has shown in vitro activity against these organisms but there are not enough clinical data to support an indication for vancomycin-resistant enterococci. Daptomycin may be an alternative to linezolid and quinupristin-dalfopristin for skin and skin structure infections. Currently, linezolid is approved for S aureus (methicillin-susceptible and resistant), S pyogenes, and S agalactiae, and quinupristin-dalfopristin is approved for methicillin-susceptible S aureus and S pyogenes. The ultimate role of daptomycin will be defined with broader clinical studies/experience.
Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente, and Assistant Clinical Professor of Medicine, University of California-San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Both are associate editors of Internal Medicine Alert.
References
1. Cubicin Product Information. Cubist Pharmaceuticals. September 2003.
2. Richter SS, et al. J Antimicrob Chemother. 2003;52(1): 123-127.
3. Rybak MJ et al. Antimicrob Agents Chemother. 2000; 44(4):1062-1066.
4. FDC Report. The Pink Sheet. September 22, 2003: 22-23.
The FDA has approved the first of a new class of antibiotics for the treatment of complicated skin and skin structure infections. Daptomycin is a cyclic lipopeptide that is active against Gram-positive bacteria.
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