Daptomycin

Summary

Daptomycin is a naturally derived cyclic lipopeptide antibiotic produced by Streptomyces roseosporus. It is used to treat serious gram-positive bacterial infections including complicated skin and skin structure infections and Staphylococcus aureus bacteremia (including right-sided endocarditis). It has a unique mechanism of action targeting the bacterial cell membrane.

Mechanism of Action

Binds to bacterial cell membranes in a calcium-dependent manner, causing rapid membrane depolarization, loss of membrane potential, inhibition of DNA, RNA, and protein synthesis, and ultimately bacterial cell death. Active against gram-positive organisms.

Routes of Administration

Goals & Uses

• MRSA osteomyelitisInfectious DiseaseModerate
• Complicated skin and skin structure infections (cSSSI)AntibacterialHigh
• Left-sided endocarditis (gram-positive)Infectious DiseaseModerate
• Staphylococcus aureus bacteremiaInfectious DiseaseHigh
• Vancomycin-resistant Enterococcus (VRE) infectionsInfectious DiseaseModerate

Contraindications

• PneumoniaDisease SpecificHigh
• Known hypersensitivity to daptomycinAllergyHigh

Adverse Effects

• Peripheral neuropathyNeurologicalUncommon
• Skeletal muscle toxicity (myopathy/rhabdomyolysis)MusculoskeletalUncommon
• Gastrointestinal disturbancesGastrointestinalCommon
• Eosinophilic pneumoniaPulmonaryRare
• Elevated liver enzymesHepaticUncommonIncrease in AST/ALT or other hepatic markers
• Infusion site reactionsLocalCommon

Drug Interactions

• TobramycinLow
• HMG-CoA reductase inhibitors (statins)Moderate
• WarfarinModerate

Population Constraints

• PregnancyReproductive SafetyRelative
• Pediatric patients (<1 year)AgeAbsolute
• Renal impairment (CrCl <30 mL/min)RenalRelative
• Pre-existing myopathy or elevated CKMusculoskeletalRelative

Regulatory Status

• European UnionApprovedApproved: Complicated skin and soft tissue infections, Staphylococcus aureus bacteremia, Right-sided infective endocarditisApproved by EMA; marketed as Cubicin in Europe
• United StatesApprovedApproved: Complicated skin and skin structure infections (adults and pediatric ≥1 year), Staphylococcus aureus bloodstream infections (bacteremia) including right-sided infective endocarditis in adultsApproved by FDA in 2003 (Cubicin); Cubicin RF approved 2016; manufactured by Merck (formerly Cubist)
• United KingdomApprovedApproved: Complicated skin and soft tissue infections, Staphylococcus aureus bacteremia and right-sided endocarditisApproved via MHRA; retained EU approval post-Brexit

FDA approved in 2003 (Cubicin). Also approved in Europe and other jurisdictions. Not indicated for pneumonia due to inactivation by pulmonary surfactant. Cubicin RF (reformulated) approved 2016.

Evidence & Sources

No sources recorded yet.