From the Guidelines
Daptomycin is a reasonable alternative to vancomycin for adults in the treatment of S aureus bacteremia and right-sided infective endocarditis, with a recommended dose of 6 mg/kg IV once daily 1.
Key Considerations for Daptomycin Use
- Daptomycin provides excellent coverage against gram-positive organisms, including MRSA, MSSA, and VRE.
- The standard dosing for daptomycin is 4-6 mg/kg IV once daily for skin and soft tissue infections.
- Higher doses of 8-12 mg/kg IV once daily are recommended for bacteremia, endocarditis, and other serious infections, although the FDA-approved dose for S aureus bacteremia and right-sided IE is 6 mg/kg IV once daily 1.
- Daptomycin works by binding to bacterial cell membranes, causing rapid depolarization and inhibition of protein, DNA, and RNA synthesis, leading to bacterial cell death.
- Important considerations when using daptomycin include monitoring creatine phosphokinase (CPK) levels weekly due to potential muscle toxicity, avoiding use in pneumonia cases (as it is inactivated by pulmonary surfactant), and adjusting dosing in patients with renal impairment 1.
Clinical Evidence and Recommendations
- A multinational trial found daptomycin to be noninferior to standard therapy with vancomycin or an antistaphylococcal penicillin plus low-dose, short-course gentamicin for S aureus bacteremia and right-sided IE 1.
- An observational study found high-dose daptomycin (≈9 mg/kg per dose) to be as effective as standard-of-care therapy for left-sided IE, with faster clearance of MRSA bacteremia 1.
- The 2023 guidelines on the contemporary management of Staphylococcus aureus bacteremia recommend daptomycin as an alternative to vancomycin, with a dose of 6 mg/kg IV once daily, although some experts argue for higher doses of 8-12 mg/kg IV once daily 1.
Administration and Safety
- Daptomycin should be administered as a 30-minute IV infusion for doses ≤6 mg/kg and as a 2-hour infusion for higher doses to minimize infusion reactions.
- Monitoring of CPK levels is crucial to minimize the risk of muscle toxicity, and dosing adjustments should be made in patients with renal impairment.
From the FDA Drug Label
Daptomycin has been shown to be active against most isolates of the following microorganisms both in vitro and in clinical infections Gram-Positive Bacteria Enterococcus faecalis (vancomycin-susceptible isolates only) Staphylococcus aureus (including methicillin-resistant isolates) Streptococcus agalactiae Streptococcus dysgalactiae subsp. equisimilis Streptococcus pyogenes
Daptomycin coverage includes Gram-Positive Bacteria, specifically:
- Enterococcus faecalis (vancomycin-susceptible isolates only)
- Staphylococcus aureus (including methicillin-resistant isolates)
- Streptococcus agalactiae
- Streptococcus dysgalactiae subsp. equisimilis
- Streptococcus pyogenes 2
From the Research
Daptomycin Coverage
- Daptomycin is a cyclic lipopeptide antibiotic with rapid bactericidal activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis and Enterococcus faecium (VRE) 3.
- It is approved for the treatment of complicated skin and soft-tissue infections (cSSTIs) caused by Gram-positive bacteria, and Staphylococcus aureus bacteraemia associated with right-sided infective endocarditis (RIE) or cSSTIs, or RIE due to S. aureus 4, 5.
- Daptomycin has been shown to be effective against a wide variety of Gram-positive bacteria, including MRSA and vancomycin-resistant enterococci, and is suitable for empirical therapy in patients with serious Gram-positive infections 5.
- The safety and efficacy of daptomycin have been compared to conventional antibiotics, such as penicillinase-resistant penicillins and vancomycin, and have been found to be comparable 6.
- Daptomycin resistance in Gram-positive bacteria is uncommon, but there are increasing reports of resistance in Staphylococcus aureus, Enterococcus faecium, and Enterococcus faecalis, particularly in the context of prolonged treatment courses and infections with high bacterial burdens 7.
Indications for Daptomycin
- Complicated skin and soft-tissue infections (cSSTIs) caused by Gram-positive bacteria 4, 5.
- Staphylococcus aureus bacteraemia associated with right-sided infective endocarditis (RIE) or cSSTIs, or RIE due to S. aureus 4, 5.
- Bacteraemia, endocarditis, cSSTIs, and osteomyelitis 4.
- Meningitis, sepsis, and urinary tract infections caused by Gram-positive bacteria 7.