Daptomycin

Cubicin, Cubicin RF, LY146032

Antimicrobial & antiviral

Awaiting medical reviewEN ES DE FR PT ZH+ Follow for updates

Note on this profile. Daptomycin is an approved intravenous antibiotic reserved for serious Gram-positive infections, including MRSA. It is a lipopeptide, so chemically it belongs on a peptide reference, but it is a hospital drug with no self-directed or community use. This page explains the published science.

Summary

Class: Cyclic lipopeptide antibiotic: a 13-amino-acid peptide (10-residue ring plus 3-residue tail) carrying a 10-carbon fatty acid, produced by the soil bacterium Streptomyces roseosporus; contains several non-standard amino acids (kynurenine, ornithine, 3-methylglutamate)
Mechanism: In the presence of calcium it inserts its fatty tail into the bacterial cell membrane, forms clusters, and lets ions leak out, killing the cell quickly without lysing it
Routes studied: Intravenous only (injection over 2 min or infusion over 30 min)
Half-life: ~8–9 h with normal kidneys; up to ~30 h in severe renal impairment
Storage: Vials refrigerated 2–8 °C (Cubicin) or room temperature (Cubicin RF); reconstituted solution stable 12 h at room temperature or 48 h refrigerated
Regulatory status: Approved medicine (US 2003, EU 2006, UK, AU, ZA and others); hospital use

Doses are as reported in studies or by the community — never recommendations.

1What it is

Daptomycin was discovered by Eli Lilly in the early 1980s from a soil actinomycete, then shelved in 1991 after muscle toxicity appeared with twice-daily dosing. Cubist Pharmaceuticals licensed it in 1997, showed that once-daily dosing largely avoided the muscle problem, and won FDA approval in 2003 for complicated skin infections and in 2006 for S. aureus bloodstream infection and right-sided heart-valve infection. It was the first new class of antibiotic for Gram-positive bacteria in decades and remains one of the main alternatives to vancomycin for MRSA and the main drug for vancomycin-resistant enterococci (VRE) in the blood.

It belongs to a family of calcium-dependent lipopeptide antibiotics that bacteria make to compete with each other; the peptide ring provides target recognition and the fatty tail provides membrane insertion. It is included on this site as a chemically genuine peptide with a mechanism unlike anything else here.

2How it's thought to work

Daptomycin binds calcium, which changes its shape and lets the decanoyl tail insert into membranes rich in phosphatidylglycerol — a lipid abundant in Gram-positive bacterial membranes and scarce in human cells.

Inserted molecules cluster (oligomerise) and disrupt the membrane, causing potassium to leak out, the membrane potential to collapse, and synthesis of DNA, RNA and protein to stop. Recent work suggests it also binds and blocks cell-wall precursors (lipid II) at the division site.

Bacteria die quickly (it is rapidly bactericidal, concentration-dependent) without bursting, which may release fewer inflammatory fragments.

It cannot cross the outer membrane of Gram-negative bacteria, so it has no activity against them.

Lung surfactant binds and inactivates it, which is why it failed in pneumonia trials and must not be used for lung infections.

A lipopeptide that inserts into the bacterial membrane and oligomerises into a pore, letting potassium out and collapsing the membrane potential. It requires calcium to insert at all, and lung surfactant inactivates it, which is why it is not used for pneumonia.Schematic — not to scale

3What the research shows

Complicated skin and skin-structure infections

Two randomised, blinded Phase 3 trials (n=1,092) found daptomycin 4 mg/kg non-inferior to vancomycin or penicillinase-resistant penicillins (clinical success 83% vs 84%) (Arbeit 2004, Clin Infect Dis). [3]

S. aureus bacteraemia and right-sided endocarditis

An open-label randomised trial (n=246) found daptomycin 6 mg/kg non-inferior to standard therapy (vancomycin or anti-staphylococcal penicillin, each with initial gentamicin): success 44% vs 42% overall, with less kidney injury in the daptomycin arm but more cases of rising MIC (emerging resistance) during therapy (Fowler 2006, NEJM). Left-sided endocarditis numbers were too small to show efficacy and it is not approved for that. [5]

Graded A (negative)

Community-acquired pneumonia

Two Phase 3 trials found daptomycin inferior to ceftriaxone, explained by surfactant inactivation (Pertel 2008, Clin Infect Dis; mechanism Silverman 2005, J Infect Dis). [4][6]

High-dose and combination therapy for VRE and MRSA

Observational cohorts and small trials suggest 8–12 mg/kg/day is safe and may improve outcomes in enterococcal bacteraemia and in MRSA with high vancomycin MICs; combination with β-lactams (ceftaroline, ampicillin) is used to prevent resistance and exploit synergy (Britt 2017, Clin Infect Dis — VRE dose comparison; Geriak 2019, Antimicrob Agents Chemother). CAMERA2 (n=352) found adding an anti-staphylococcal β-lactam to vancomycin or daptomycin for MRSA bacteraemia did not improve outcomes and caused more kidney injury (Tong 2020, JAMA). [7][8]

Graded B/A

Osteomyelitis, prosthetic joint infection, paediatric infections

Registry data (EU-CORE) and paediatric (Bradley 2017, Pediatrics) support use; osteomyelitis use is off-label but common.

Community / self-directed use

None documented.

4Reported side effects and interactions

Literature-reported

Raised creatine phosphokinase (CPK) in about 3–7%, with symptomatic myopathy in under 1% and rare rhabdomyolysis — more likely with higher doses, renal impairment and concurrent statins; eosinophilic pneumonia (cough, fever, breathlessness, typically 2–4 weeks into therapy; resolves on stopping, often needs steroids); drug reaction with eosinophilia and systemic symptoms (DRESS), tubulointerstitial nephritis; peripheral neuropathy (rare); Clostridioides difficile diarrhoea; false prolongation of prothrombin time/INR with some lab reagents (a test artefact — redraw just before the next dose). Common minor effects: constipation, nausea, headache, insomnia, injection-site reactions.

Community-reported

none; no community use.

Theoretical. resistance via membrane-charge mutations (mprF, liaFSR) develops during therapy, especially in deep-seated infections with low drug exposure — the main long-term concern.

Interactions. statins — the label suggests considering temporarily suspending them because of additive myopathy risk; no CYP interactions (it is not metabolised by P450); laboratory interaction with recombinant thromboplastin PT/INR reagents as above; additive nephrotoxicity is not expected but renal function governs dosing.

Markers researchers commonly monitor

These follow the label and infectious-disease practice:

Marker	Why it's watched
Creatine phosphokinase (CPK)	baseline and at least weekly; more often (e.g. twice weekly) in patients on statins, with renal impairment, or on doses above 6 mg/kg; stop if CPK exceeds ~5× upper limit with symptoms or ~10× without.
Serum creatinine / creatinine clearance	determines dosing interval and myopathy risk.
Blood cultures (repeat until clear)	the efficacy marker in bacteraemia; persistent positivity prompts MIC retesting for emerging resistance.
Daptomycin MIC on isolates during prolonged therapy	rising MIC (≥2 µg/mL) signals non-susceptibility.
Eosinophil count, oxygen saturation and chest imaging if cough or fever develop	eosinophilic pneumonia surveillance.
Prothrombin time / INR timing	if monitored for other reasons, draw just before the next dose to avoid the assay artefact.
Symptoms of muscle pain or weakness and peripheral neuropathy	asked about at each review.

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

Hospital pharmacy preparation: a 350 mg or 500 mg vial is with 7 mL or 10 mL of 0.9% saline (or for Cubicin RF) to 50 mg/mL, left to stand and then swirled gently — not shaken — to avoid foaming, which can take several minutes; it is given over 2 minutes by IV push or diluted in saline for a 30-minute infusion. Incompatible with dextrose-containing . Reconstituted vials are stable 12 h at room temperature or 48 h refrigerated (combined with any infusion time). The site calculator is not applicable.

6Commonly studied alongside

Vancomycin (the standard comparator and alternative), linezolid, ceftaroline, ampicillin, gentamicin and rifampicin (combination regimens for endocarditis, prosthetic infections and VRE), fosfomycin (synergy studies). Related antimicrobial peptides on this site — LL-37 and other host-defence peptides (earlier profiles) — share the membrane target in principle but have no clinical overlap.

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	FDA-approved (Cubicin, September 2003; bacteraemia/endocarditis 2006; paediatric 2017); generics since 2016; Cubicin RF room-temperature formulation 2016
European Union	EMA-authorised (Cubicin, January 2006, MSD) for complicated skin infections, right-sided endocarditis and S. aureus bacteraemia in adults and children; generics authorised
United Kingdom	MHRA-licensed (Cubicin and generics); hospital only
Australia	TGA-registered (Cubicin and generics)
South Africa	Registered with SAHPRA (Cubicin and generics) †
Sport	Not prohibited by WADA

8Open questions

Optimal dose for deep-seated and enterococcal infections: 6, 8, 10 or 12 mg/kg — evidence is thin.
Whether β-lactam combinations prevent resistance and improve survival (CAMERA2 says no for MRSA bacteraemia; VRE data are observational).
Mechanisms behind eosinophilic pneumonia and how to predict it.

9References

1Debono M et al. (1987). A21978C, a complex of new acidic peptide antibiotics: isolation, chemistry, and mass spectral structure elucidation. J Antibiot (Tokyo). PubMed · DOI
2Silverman JA et al. (2003). Correlation of daptomycin bactericidal activity and membrane depolarization in Staphylococcus aureus. Antimicrob Agents Chemother. PubMed · DOI
3Arbeit RD et al. (2004). The safety and efficacy of daptomycin for the treatment of complicated skin and skin-structure infections. Clin Infect Dis. PubMed · DOI
4Silverman JA et al. (2005). Inhibition of daptomycin by pulmonary surfactant: in vitro modeling and clinical impact. J Infect Dis. PubMed · DOI
5Fowler VG et al. (2006). Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus. NEJM. PubMed · DOI
6Pertel PE et al. (2008). Effects of prior effective therapy on the efficacy of daptomycin and ceftriaxone for the treatment of community-acquired pneumonia. Clin Infect Dis. PubMed · DOI
7Tong SYC et al. (2020). Effect of vancomycin or daptomycin with vs without an antistaphylococcal β-lactam on mortality, bacteremia, relapse, or treatment failure in patients with MRSA bacteremia (CAMERA2). JAMA. PubMed · DOI
8Britt NS et al. (2017). Comparative effectiveness and safety of standard-, medium-, and high-dose daptomycin strategies for the treatment of vancomycin-resistant enterococcal bacteremia among Veterans Affairs patients. Clin Infect Dis. PubMed · DOI
9Cubicin (daptomycin for injection) US prescribing information and EU Summary of Product Characteristics (current). PubMed

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.

10Community

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Self-reported side effects Phase 2

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11Page history

30 Oct 2026Profile published — awaiting medical review

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