Peptide education
Daptomycin
Cubicin · Cubicin RF
Daptomycin is an intravenous antibiotic for certain serious Gram-positive infections. The Cubicin RF label covers specified complicated skin infections and Staphylococcus aureus bloodstream infections.
In a randomized bacteremia trial, daptomycin met the prespecified noninferiority criterion against a standard-therapy strategy that included initial gentamicin and either vancomycin or a penicillin.
Overview
Quick answer
The adult bloodstream indication includes right-sided infective endocarditis. The label does not indicate daptomycin for pneumonia or left-sided S. aureus endocarditis.
Which bacteria does the skin-infection label name?
Susceptible organisms include S. aureus, including methicillin-resistant isolates, certain streptococci, and vancomycin-susceptible Enterococcus faecalis.
Is it used for pneumonia?
No. Cubicin RF is not indicated for pneumonia.
What did the bloodstream infection trial compare?
It compared daptomycin with initial low-dose gentamicin plus either vancomycin or an antistaphylococcal penicillin. The main result is for that combined comparator, not vancomycin alone.
What needs monitoring?
The label advises monitoring for muscle pain or weakness and measuring creatine phosphokinase. Kidney impairment also affects dosing and monitoring.
Does the label cover children of every age?
The label covers specified skin infections and S. aureus bacteremia in children aged 1 to 17 years. It does not recommend use below age 1 because of muscle and nervous-system effects observed in neonatal dogs.
Evidence
Evidence snapshot
Treatment success with daptomycin versus pooled standard therapy at 42 days after treatment, in the modified intention-to-treat analysis. The difference was 2.4 percentage points, with a 95% confidence interval from -10.2 to 15.1.
This describes the prespecified comparison, not superiority.
Number of children in the daptomycin and standard-care groups in the intention-to-treat population.
The label warns about muscle injury and eosinophilic pneumonia.
Claims
Common claims vs evidence
| Claim | Human evidence | Verdict |
|---|---|---|
| Daptomycin treats all infections caused by S. aureus. | The label covers defined skin and bloodstream infections, including right-sided endocarditis in adults. It excludes pneumonia and left-sided S. aureus endocarditis from the indications. | Infection site and susceptibility are essential distinctions. |
| The bacteremia trial proved daptomycin superior to vancomycin alone. | Daptomycin met a noninferiority criterion against a pooled standard strategy of gentamicin plus vancomycin or an antistaphylococcal penicillin. | The study did not establish that claim. |
| A good infection response removes the need for monitoring. | The label warns of myopathy and rhabdomyolysis and calls for creatine phosphokinase monitoring during treatment. | Clinical response and treatment safety are separate considerations. |
Bottom line
Main takeaway
Daptomycin is not indicated for pneumonia.
Muscle pain or weakness and new respiratory symptoms warrant clinical attention during treatment.
The bacteremia result compares daptomycin with a combined standard-therapy strategy.
Identity
What it is
Cubicin RF is a prescription lipopeptide antibiotic given intravenously.
The label names susceptible Gram-positive bacteria for complicated skin infections and S. aureus, including MRSA, for bloodstream infection.
Use context
Routes, doses, and cycle patterns
The U.S. label specifies different adult doses for skin and bloodstream infections.
Human studies and product labels
Adult complicated skin infection
- Purpose
- Labeled treatment of susceptible complicated skin and skin structure infection
- Context
- U.S. prescription label
- Route
- Intravenous
- Amount
- 4 mg/kg
- Frequency
- Every 24 hours when creatinine clearance is at least 30 mL/min
- Duration
- 7 to 14 days
The interval changes to every 48 hours below a creatinine clearance of 30 mL/min.
Adult S. aureus bacteremia
- Purpose
- Bloodstream infection, including right-sided infective endocarditis
- Context
- U.S. prescription label
- Route
- Intravenous
- Amount
- 6 mg/kg
- Frequency
- Every 24 hours when creatinine clearance is at least 30 mL/min
- Duration
- 2 to 6 weeks
The label changes the interval to every 48 hours below a creatinine clearance of 30 mL/min. Pediatric doses are age-based.
Bacteremia trial
- Purpose
- S. aureus bacteremia with or without endocarditis
- Context
- Study-reported randomized regimen
- Route
- Intravenous
- Amount
- 6 mg/kg daily
- Frequency
- Once daily
The comparator was initial gentamicin plus vancomycin or an antistaphylococcal penicillin.
What varies
- Kidney function: the adult dose interval changes with severe renal impairment.
- Infection site: pneumonia and left-sided S. aureus endocarditis are not labeled indications.
Research
Research evidence
Controlled human studies include an adult S. aureus bacteremia trial and a pediatric complicated-skin-infection trial. Their populations and endpoints differ.
| Study / evidence area | Population | Design | Product context | Main outcome | Limitations | Weight |
|---|---|---|---|---|---|---|
| S. aureus bacteremia and endocarditis | Patients with S. aureus bacteremia, with or without endocarditis | Randomized active-comparator trial | IV daptomycin versus gentamicin plus vancomycin or penicillin | Success at 42 days after treatment was 53 of 120 versus 48 of 115. | The comparator was pooled, and reduced susceptibility emerged in some failures. | Strong |
| Pediatric complicated skin infection | Children and adolescents aged 1 to 17 years with complicated skin infections | Randomized active-comparator safety study | Age-based IV daptomycin versus standard antibiotics | The publication reports 91% clinical success with daptomycin; the label reports 227 of 257, or 88%. | Safety was the primary objective, and approximately 95% switched to oral antibiotics. The sources report different success percentages; the reason is not established here. | Moderate |
Cautions
Safety and unknowns
- The label warns of myopathy and rhabdomyolysis and calls for creatine phosphokinase monitoring.
- Eosinophilic pneumonia and serious hypersensitivity reactions are listed warnings.
- Renal impairment changes the adult dosing interval; the label advises more frequent renal function and muscle enzyme monitoring in these patients.
- The label does not recommend use below age 1 because of muscle and nervous-system effects observed in neonatal dogs.
Product quality
Product identity and quality
Cubicin RF is a sterile prescription product prepared for intravenous administration.
Formulation
Daptomycin formulations can have different reconstitution and storage instructions.
Mechanism
How it is proposed to work
Daptomycin acts on bacterial cell membranes and disrupts their electrical potential.
A laboratory study found calcium-dependent loss of membrane potential in S. aureus. The drug label describes downstream inhibition of bacterial protein, DNA, and RNA synthesis.
FAQ
Common questions
Is daptomycin indicated for pneumonia?
No. Cubicin RF is not indicated for pneumonia.
Does the adult dose change with severe renal impairment?
Yes. For adults with creatinine clearance below 30 mL/min, the label changes the interval from every 24 hours to every 48 hours.
Details
Technical details
Sources
References
- 1.
DailyMed. Cubicin RF prescribing information
- 2.
PubMed. Daptomycin versus standard therapy for Staphylococcus aureus bacteremia and endocarditis
doi:10.1056/NEJMoa053783 PMID:16914701 NCT00093067
- 3.
PubMed. Daptomycin for complicated skin infections in children
doi:10.1542/peds.2016-2477 PMID:28202770
- 4.
PubMed. Daptomycin and membrane potential in Staphylococcus aureus
doi:10.1128/AAC.35.11.2282 PMID:1666494