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| {{drugbox | | __NOTOC__ |
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| | {{Daptomycin}} |
| | IUPAC_name = ''N''-decanoyl-L-tryptophyl-L-asparaginyl-L-aspartyl-L-threonylglycyl-<BR>L-ornithyl-L-aspartyl-D-alanyl-L-aspartylglycyl-D-seryl-''threo'' -3-methyl-L-glutamyl-3-anthraniloyl-L-alanine[egr]<sub>1</sub>-lactone
| | {{CMG}};{{AE}}{{AK}} |
| | image = Daptomycin2.png
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| | CAS_number = 103060-53-3
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| | ATC_prefix = J01
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| | ATC_suffix = XX09
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| | PubChem = 14171
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| | DrugBank = BTD00111
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| | C = 72 | H = 101 | N = 17 | O = 26
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| | molecular_weight = 1619.7086 g/mol
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| | bioavailability = n/a
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| | protein_bound = 90–95%
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| | metabolism = Renal (speculative)<ref>Woodworth JR, Nyhart EH, Brier GL, ''et al.'' Single-dose pharmacokinetics and antibacterial activity of daptomycin, a new lipopeptide antibiotic, in healthy volunteers. Antimicrob Agents Chemother 1992;36(2):318-325. PMID 1318678</ref>
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| | elimination_half-life = 7–11 hours (up to 28 hours in renal impairment)
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| | excretion = [[Kidney|Renal]] (78%; primarily as unchanged drug); Faeces (5.7%)
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| | pregnancy_US = B
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| | legal_US = Rx-only
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| | routes_of_administration = [[Intravenous]]
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| }} | |
| {{SI}} | |
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| | ==Overview== |
| '''Daptomycin''' is a novel [[lipopeptide]] [[antibiotic]] used in the treatment of certain infections caused by [[Gram-positive]] organisms. It is a naturally-occurring compound found in the soil [[saprotroph]] ''[[Streptomyces roseosporus]]''. Its distinct mechanism of action means that it may be useful in treating infections caused by multi-resistant bacteria. It is marketed in the United States under the trade name '''Cubicin''' ([[Cubist Pharmaceuticals]]). | | '''Daptomycin''' is a novel [[lipopeptide]] [[antibiotic]] used in the treatment of certain infections caused by [[Gram-positive]] organisms. It is a naturally-occurring compound found in the soil [[saprotroph]] ''[[Streptomyces roseosporus]]''. Its distinct mechanism of action means that it may be useful in treating infections caused by multi-resistant bacteria. It is marketed in the United States under the trade name '''Cubicin''' ([[Cubist Pharmaceuticals]]). |
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| ==History== | | ==Category== |
| The compound was originally discovered by researchers at [[Eli Lilly and Company]] in the 1980s, who designated the compound '''LY 146032'''.
| | Cyclic lipopeptide |
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| The compound showed promise in Phase I/II [[clinical trial]]s for the treatment of infections caused by Gram-positive organisms. However, high dose therapy was found to be associated with adverse effects on skeletal muscle, including [[myalgia]] and the potential for [[myositis]], and Lilly ceased development. The rights to LY 146032 were subsequently acquired by [[Cubist Pharmaceuticals]] in 1997, which subsequently marketed the drug under the trade name ''CUBICIN'' following U.S. [[Food and Drug Administration]] (FDA) approval in November 2003. CUBICIN is marketed in the EU and several other countries by [[Novartis]] following its buying of [[Chiron Corporation]], whom previously held those licences. Outside of the US, CUBICIN is available in [[Germany]] and the [[UK]], with further launches expected in [[2007]].<ref name="Tally2000">Tally FP, DeBruin MF. Development of daptomycin for Gram-positive infections. J Antimicrob Chemother 2000;46(4):523-6. PMID 11020247.</ref><ref name="Charles 2004">Charles PG, Grayson ML. The dearth of new antibiotic development: why we should be worried and what we can do about it. Med J Aust 2004;181(10):549-53. PMID 15540967</ref>
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| ==Pharmacology==
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| Daptomycin has a distinct mechanism of action, disrupting multiple aspects of bacterial [[cell membrane]] function. It appears to bind to the membrane and cause rapid [[depolarisation]], resulting in a loss of membrane potential leading to inhibition of [[protein]], [[DNA]] and [[RNA]] synthesis, which results in bacterial cell death.
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| The bactericidal activity of daptomycin is concentration-dependent. There is ''in vitro'' evidence of synergy with [[Beta-lactam|β-lactam]] antibiotics.
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| ==Microbiology==
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| Daptomycin is active against Gram-positive bacteria only. It has proven ''in vitro'' activity against [[Enterococcus|enterococci]] (including [[glycopeptide]]-resistant Enterococci (GRE)), [[Staphylococcus|staphylococci]] (including [[methicillin-resistant Staphylococcus aureus|methicillin-resistant ''Staphylococcus aureus'']]), [[Streptococcus|streptococci]] and [[Corynebacterium|corynebacteria]].
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| ==Clinical use==
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| ===Indications===
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| Daptomycin is approved in the United States for skin and skin structure infections caused by Gram-positive infections, ''[[Staphylococcus aureus]]'' bacteraemia and right-sided ''S. aureus'' [[endocarditis]].
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| ===Efficacy===
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| Daptomycin has been shown to be not inferior to standard therapies ([[nafcillin]], [[oxacillin]], [[flucloxacillin]] or [[vancomycin]]) in the treatment of [[bacteraemia]] and right-sided [[endocarditis]] caused by ''Staphylococcus aureus''.<ref name="Fowler2006">Fowler VG Jr, Boucher HW, Corey GR, Abrutyn E, Karchmer AW, Rupp ME, ''et al.'' Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus. N Engl J Med 2006;355(7):653-65. PMID 16914701</ref>
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| In Phase III clinical trials, limited data showed that daptomycin was associated with poor outcomes in patients with left-sided endocarditis. It is inactivated by pulmonary [[surfactant]]s and is not indicated for the treatment of [[pneumonia]]. Daptomycin has not been studied in patients with [[prosthetic heart valve|prosthetic valve]] endocarditis or [[meningitis]].<ref name="Cubist2005">Cubicin (daptomycin for injection) [homepage on the Internet]. Lexington (MA): Cubist Pharmaceuticals; c2003–06 [updated 2006 May 27; cited 2006 Aug 20]. Available from: http://www.cubicin.com/home.htm</ref>
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| ===Dosage and presentation===
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| In skin and soft tissue infections, 4 mg/kg daptomycin is given intravenously once daily. For ''S. aureus'' bacteraemia or right-sided endocarditis, the approved dose is 6 mg/kg given intravenously once daily.
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| The dose of daptomycin must be reduced in renal impairment. There is no information available on dosing in people less than 18 years of age.
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| Daptomycin is supplied as a sterile preservative-free pale yellow to light brown lyophilised 500 mg cake that must be reconstituted with 0.9% saline prior to use.
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| ===Adverse effects===
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| Adverse drug reactions associated with daptomycin therapy include:<ref name="MicromedexDrugdex">Daptomycin. In: Klasco RK, editor. Drugdex system, vol. 129. Greenwood Village (CO): Thomson Micromedex; 2006.</ref>
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| *Cardiovascular: [[hypotension]] (2.4%), [[hypertension]] (1.1%), [[edema]], cardiac failure, [[supraventricular tachycardia]]
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| *Central nervous system: headache (5.4%), insomnia (4.5%), dizziness (2.2%), anxiety, confusion, [[Vertigo (medical)|vertigo]], [[paraesthesia]]
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| *Dermatological: rash (4.3%), [[pruritus]] (2.8%), [[eczema]]
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| *Endocrine: [[hypokalaemia]], [[hyperglycemia]], [[hypomagnesemia]], increased serum [[bicarbonate]], other [[electrolyte]] disturbances
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| *Gastrointestinal: constipation (6.2%), nausea (5.8%), diarrhea (5.2%), vomiting (3.2%), dyspepsia (0.9%), abdominal pain, decreased appetite, [[stomatitis]], flatulence
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| *Hematological: [[anemia]] (2.1%), [[leukocytosis]], [[thrombocytopenia]], [[thrombocytosis]], [[eosinophilia]], increased [[international normalised ratio]] (INR)
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| *Hepatic: abnormal [[liver function test]]s (3%) (including [[alkaline phosphatase]] and [[lactate dehydrogenase]]), [[jaundice]]
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| *Musculoskeletal: elevated [[creatine kinase]] (CK) levels (2.8–10.5%), limb pain (1.5%), [[arthralgia]] (0.9%), [[myalgia]], muscle cramps, muscle weakness, [[osteomyelitis]]
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| *Renal: acute [[renal failure]] (2.2%)
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| *Respiratory: [[dyspnea]] (2.1%)
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| *Other: injection site reactions (5.8%), fever (1.9%), [[hypersensitivity]]
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| There are also reports of [[myopathy]] and [[rhabdomyolysis]] occurring in patients simultaneously taking [[statin]]s but whether this is due entirely to the statin or whether daptomycin potentiates this effect is unknown. Due to the limited data available, the manufacturer recommends that statins be temporarily discontinued while the patient is receiving daptomycin therapy.
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| ==References==
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| <div class="references-small">{{reflist|2}}</div>
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| ==External links==
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| *[http://www.ucsf.edu/idmp/whatsnew/dapto_monograph.htm UCSF monograph]
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| *[http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=14171 PubChem Substance ID]
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| *[http://www.whocc.no/atcddd/new_atc_ddd.html New ATC Codes] (from [[WHO]])
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| * {{UMichOPM|families|superfamily|172}} - Orientations of daptomycin and tsushimycin in membrane
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| {{Other antibacterials}}
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| [[Category:Antibiotics]]
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| [[Category:Peptides]]
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| [[Category:Peripheral membrane proteins]]
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| | ==US Brand Names== |
| | CUBICIN®. |
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| [[fr:Daptomycine]]
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| [[tr:Daptomisin]]
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| {{WH}}
| | ==FDA Package Insert== |
| {{WikiDoc Sources}}
| | ''' [[Daptomycin description|Description]]''' |
| | '''| [[Daptomycin clinical pharmacology|Clinical Pharmacology]]''' |
| | '''| [[Daptomycin microbiology|Microbiology]]''' |
| | '''| [[Daptomycin indications and usage|Indications and Usage]]''' |
| | '''| [[Daptomycin contraindications|Contraindications]]''' |
| | '''| [[Daptomycin warnings|Warnings]]''' |
| | '''| [[Daptomycin precautions|Precautions]]''' |
| | '''| [[Daptomycin adverse reactions|Adverse Reactions]]''' |
| | '''| [[Daptomycin overdosage|Overdosage]]''' |
| | '''| [[Daptomycin clinical studies|Clinical Studies]]''' |
| | '''| [[Daptomycin dosage and administration|Dosage and Administration]]''' |
| | '''| [[Daptomycin compatibility reconstitution and stability|Compatibility, Reconstitution, and Stability]]''' |
| | '''| [[Daptomycin directions for use|Directions For Use]]''' |
| | '''| [[Daptomycin how supplied|How Supplied]]''' |
| | '''| [[Daptomycin labels and packages|Labels and Packages]]''' |