What it is
Daptomycin is an antibiotic made of 13 amino acids, ten of them closed into a ring, with a fatty-acid tail. The label calls it "a cyclic lipopeptide antibacterial agent derived from the fermentation of Streptomyces roseosporus", a soil bacterium. Its formula is C72H101N17O26, molecular weight 1,620.67.
Read as residues, the label's chemical name gives the chain: a decanoyl group (a 10-carbon fatty acid) on tryptophan, then asparagine, aspartate, threonine, glycine, ornithine, aspartate, alanine, aspartate, glycine, serine, a 3-methyl-glutamate and a kynurenine-like residue, the last of which closes the ring back onto threonine. Three of the residues are D-forms, the mirror images of the amino acids human proteins use — a sign of bacterial manufacture.
How it works
The label's microbiology section describes daptomycin as having "rapid, concentration-dependent bactericidal activity against Gram-positive bacteria in vitro," across most clinically relevant Gram-positive pathogens. In animal models its activity tracks the ratio of total drug exposure to the bacterium's minimum inhibitory concentration (AUC/MIC); the label adds that the parameter best linked to cure in people has not been established.
What the label's trials show
| Use (label) | Trial design | Result |
|---|---|---|
| Complicated skin infections, adults | Two randomised, investigator-blinded trials (9801, 9901), 534 on daptomycin 4 mg/kg vs 558 on vancomycin or an anti-staphylococcal penicillin | Clinical success (ITT) 62.5% vs 60.9% and 80.4% vs 80.5% |
| Complicated skin infections, children 1–17 | Randomised trial, 257 vs 132 | Success at test of cure 88% (227/257) vs 86% (114/132) |
| S. aureus bacteraemia incl. right-sided endocarditis, adults | Randomised, 120 on daptomycin 6 mg/kg vs 115 on standard therapy | Adjudicated success six weeks after treatment 44.2% vs 41.7%; difference 2.4, 95% CI −10.2 to 15.1 |
The pattern in every row is similarity to standard therapy, not superiority. In the bacteraemia trial the confidence interval runs from 10 points worse to 15 points better.
Two subgroups the label itself flags. Success was lower in patients aged 65 and over in both indications. And in the bacteraemia trial, adjudicated success on daptomycin fell with kidney function — 60% (30/50) for bacteraemia patients with creatinine clearance above 80 mL/min, 14% (2/14) at 30 to under 50 — a drop the label says was not seen on the comparator.
What it is not approved for
- Pneumonia. In phase 3 trials of community-acquired pneumonia, "the death rate and rates of serious cardiorespiratory adverse events were higher in daptomycin-treated patients," differences the label attributes to lack of therapeutic effect.
- Left-sided infective endocarditis due to S. aureus.
- Infants under one year, because of muscular, neuromuscular and nervous-system effects seen in neonatal dogs — an animal finding, labelled here as such.
Doses on the label
Reported from the label, for reference; the dose for any patient is set by the treating team.
| Indication | Adults (label) |
|---|---|
| Complicated skin and skin-structure infections | 4 mg/kg once every 24 hours, for 7 to 14 days |
| S. aureus bacteraemia | 6 mg/kg once every 24 hours, for 2 to 6 weeks |
Doses above 6 mg/kg are not approved (label). With creatinine clearance below 30 mL/min, including dialysis, the label moves the same doses to once every 48 hours.
Safety
The label's warnings: anaphylaxis; myopathy and rhabdomyolysis, with CPK monitoring and stopping thresholds (above ~5× the upper limit with muscle symptoms, above ~10× without); eosinophilic pneumonia; DRESS; tubulointerstitial nephritis; peripheral neuropathy; and an increased INR (prolonged prothrombin time) on testing. In the adult skin trials, 1 of 534 patients had muscle pain or weakness with CPK above 4× normal; it resolved within days of stopping.
Where it stands
- Approved in the US since 2003-09-12 (Cubicin, Cubist, NDA 021572, a new molecular entity).
- Brand: every Cubicin and Cubicin RF product under that application is listed as discontinued.
- Generics and other forms: 25 daptomycin applications in Drugs@FDA; 19 generic and 11 other prescription intravenous products are listed (openFDA, 2026-10-11).
- Research record: PubMed indexes 4,691 records, 49 tagged as randomised trials (2026-10-11).
Related reading
Daptomycin was compared with vancomycin, a glycopeptide antibiotic, in its skin-infection trials. Another fatty-tailed peptide drug in the library is the antifungal micafungin, and the glycopeptide dalbavancin treats the same kind of skin infection with one or two infusions.