What are the clinical trials on Daptomycin (Dapt)

From the Guidelines

Daptomycin is a reasonable alternative to vancomycin for adults in the treatment of S aureus NVE, with a recommended dose of 6 mg·kg −1·d−1, although some experts suggest higher doses of 8 to 10 mg/kg for complicated infections, including left-sided IE. The use of daptomycin for the treatment of S aureus infections, including infective endocarditis, has been supported by several studies 1. Some key points to consider when using daptomycin include:

• Daptomycin is bactericidal against both MSSA and MRSA and does not require therapeutic drug monitoring 1.
• The emergence of organisms with decreased susceptibility to daptomycin was observed in ≈5% of daptomycin-treated patients, highlighting the need for careful patient selection and monitoring 1.
• Daptomycin is inhibited by pulmonary surfactant and is contraindicated in the treatment of S aureus pneumonia acquired via the aspiration route 1.
• Higher doses of daptomycin (8-12 mg/kg) may be warranted in the treatment of complicated MRSA bacteremia, particularly IE, due to its concentration-dependent bactericidal activity and pharmacokinetic studies suggesting inadequate drug exposure in certain populations 1. It is essential to weigh the benefits and risks of daptomycin use, considering factors such as the severity of the infection, patient comorbidities, and potential for resistance development 1. Additionally, other treatment options, such as vancomycin, linezolid, and ceftaroline, may be considered for the treatment of S aureus infections, depending on the specific clinical scenario and patient characteristics 1.

From the FDA Drug Label

Table 4: Clinical Success Rates by Renal Function and Treatment Group in Phase 3 cSSSI Trials in Adult Patients (Population: ITT) Table 5: Adjudication Committee Clinical Success Rates at Test of Cure by Baseline Creatinine Clearance and Treatment Subgroup in the S aureus Bacteremia/Endocarditis Trial in Adult Patients (Population: ITT) Table 6: Incidence of Adverse Reactions that Occurred in ≥2% of Adult Patients in the Daptomycin for Injection Treatment Group and ≥ the Comparator Treatment Group in Phase 3 cSSSI Trials

The trials on daptomycin include:

• Phase 3 cSSSI trials: evaluated the clinical success rates of daptomycin in adult patients with complicated skin and skin structure infections.
• S aureus bacteremia/endocarditis trial: assessed the clinical success rates of daptomycin in adult patients with S aureus bacteremia or endocarditis. The results of these trials are presented in the tables above, showing the clinical success rates and adverse reaction rates for daptomycin-treated patients compared to comparator-treated patients 2. Key findings include:
• Clinical success rates were lower in patients with baseline creatinine clearance <50 mL/min.
• Adverse reactions, such as diarrhea, headache, and rash, were reported in ≥2% of adult patients receiving daptomycin.
• Serious Gram-negative infections were reported in 8.3% of daptomycin-treated patients in the S aureus bacteremia/endocarditis trial.

From the Research

Daptomycin Trials

• Daptomycin is a cyclic lipopeptide antibiotic used to treat complicated skin and skin-structure infections (cSSSI) caused by gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) 3, 4, 5.
• The efficacy and safety of daptomycin have been evaluated in several clinical trials, including a pilot study that compared high-dose short-duration daptomycin with standard therapy for cSSSI 3.
• In this study, the clinical success rates were 75.0% for daptomycin and 87.5% for the comparator, with a safety profile similar to that seen in previous studies 3.
• Another study compared daptomycin with conventional antibiotics for the treatment of cSSSI and found that the clinical success rates were 83.4% and 84.2% for the daptomycin- and comparator-treated groups, respectively 4.
• A review of the use of daptomycin in the management of cSSSI and Staphylococcus aureus bacteraemia found that it was effective and well-tolerated, with a low potential for drug interactions 5.

Daptomycin Dosage and Administration

• Daptomycin is typically administered at a dose of 4 mg/kg intravenously every 24 hours for 7-14 days 4, 6.
• The dosage may need to be adjusted in patients with reduced renal function, including those receiving hemodialysis and peritoneal dialysis 6.
• Daptomycin has a volume of distribution of 0.1 L/kg and a plasma elimination half-life of approximately 9 hours, and is eliminated primarily by renal excretion 6.

Clinical Experience with Daptomycin

• A multicenter observational registry found that daptomycin was effective in treating cSSSI due to culture-confirmed MRSA and MSSA, with clinical success rates of 89.1% overall, including 89.7% and 85.0% of those with MRSA and MSSA, respectively 7.
• The registry also found that the total days of daptomycin therapy and the days to clinical response were not significantly different for MRSA and MSSA patients 7.