From the Guidelines
Yes, MRSA (Methicillin-resistant Staphylococcus aureus) is typically susceptible to daptomycin, making it an effective treatment option for MRSA infections. Daptomycin is a lipopeptide antibiotic that works by binding to bacterial cell membranes and causing rapid depolarization, leading to inhibition of protein, DNA, and RNA synthesis, which results in bacterial cell death. It is particularly useful for treating serious MRSA infections including complicated skin and skin structure infections, bacteremia, and right-sided endocarditis. The typical adult dosage ranges from 4-6 mg/kg administered intravenously once daily for skin infections, and 6-10 mg/kg once daily for bacteremia or endocarditis, with treatment duration typically ranging from 7-14 days for skin infections and 2-6 weeks for more serious infections, depending on clinical response. Some experts recommend higher doses of daptomycin, such as 8-12 mg/kg, for complicated infections, including left-sided endocarditis, due to its concentration-dependent bactericidal activity and pharmacokinetic studies suggesting inadequate drug exposure in certain populations 1. It's essential to note that while MRSA resistance to daptomycin is relatively uncommon, it can develop during therapy, particularly in patients with deep-seated infections or prolonged treatment. Regular monitoring of creatine phosphokinase (CPK) levels is recommended during daptomycin therapy due to potential muscle toxicity, and the drug should be used cautiously in patients with renal impairment, with appropriate dose adjustments 1. The emergence of organisms with decreased susceptibility to daptomycin was observed in approximately 5% of daptomycin-treated patients, highlighting the need for careful patient selection and monitoring 1. Overall, daptomycin is a valuable treatment option for MRSA infections, and its use should be guided by the most recent clinical guidelines and evidence-based recommendations 1.
From the FDA Drug Label
The overall Adjudication Committee success rates in the ITT population were 44. 2% (53/120) in patients treated with daptomycin for injection and 41.7% (48/115) in patients treated with comparator (difference = 2.4% [95% CI −10.2,15.1]). The success rates in the PP population were 54.4% (43/79) in patients treated with daptomycin for injection and 53.3% (32/60) in patients treated with comparator (difference = 1.1% [95% CI −15.6,17. 8]). Methicillin-resistant S. aureus 20/45 (44%) 14/44 (32%) 12.6% (−10.2,35.5) Among patients with persisting or relapsing S. aureus infections, 8/19 daptomycin for injection-treated patients and 7/11 comparator-treated patients died Failure of treatment due to persisting or relapsing S aureus infections was assessed by the Adjudication Committee in 19/120 (16%) daptomycin for injection-treated patients (12 with MRSA and 7 with MSSA) and 11/115 (10%) comparator-treated patients (9 with MRSA treated with vancomycin and 2 with MSSA treated with an anti-staphylococcal semi-synthetic penicillin)
Daptomycin susceptibility in MRSA:
- The drug label shows that daptomycin has a success rate of 44% in treating MRSA infections.
- The median time to clearance of MRSA bacteremia was 8 days.
- Failure of treatment due to persisting or relapsing MRSA infections occurred in 12 out of 120 patients treated with daptomycin.
- Key finding: Daptomycin appears to be effective against MRSA, with a success rate comparable to the comparator (vancomycin). 2
From the Research
Susceptibility of MRSA to Daptomycin
- MRSA is typically susceptible to daptomycin, as evidenced by its in vitro activity against a wide variety of Gram-positive bacteria, including MRSA 3, 4, 5.
- Daptomycin has been shown to be effective in treating MRSA infections, including bacteremia, right-sided endocarditis, and complicated skin and skin structure infections 3, 4, 6.
- The mechanism of action of daptomycin involves a calcium-dependent dissipation of membrane potential, leading to the release of intracellular ions and bacterial death 5.
Clinical Use of Daptomycin
- Daptomycin is approved for the treatment of complicated skin and skin structure infections, right-sided endocarditis, and bacteremia caused by Gram-positive bacteria, including MRSA 3, 4.
- Daptomycin can be used as monotherapy or in combination with other antibiotics, such as β-lactams, to treat complicated MRSA bacteremia 7.
- Combination therapy with daptomycin and other antibiotics may offer a promising treatment option for complicated MRSA bacteremia, particularly in cases where emergence of resistance is anticipated 7.
Resistance to Daptomycin
- Emerging cases of resistance to daptomycin have been reported, commonly occurring by spontaneous mutations, and have been associated with prolonged use, osteomyelitis, acute myeloid leukemia, and leucocyte adhesion deficiency syndrome 5.
- The development of resistance to daptomycin is a concern, and combination therapy with other antibiotics may help to reduce the risk of resistance 7.