Is daptomycin effective against Vancomycin-Resistant Enterococcus (VRE)?

From the Guidelines

Daptomycin is effective against Vancomycin-Resistant Enterococcus (VRE) and is considered an important treatment option for these infections, with a recommended dose of 8-12 mg/kg IV once daily for serious infections like bacteremia or endocarditis. The effectiveness of daptomycin against VRE is supported by a meta-analysis of 2 cohort studies, which found a significant reduction in 30-day mortality rate in patients treated with high-dose daptomycin compared to standard dose 1. Additionally, a study published in the Journal of Microbiology, Immunology and Infection found that daptomycin had better in vitro bactericidal activity against VRE than other antimicrobial agents, including vancomycin, linezolid, and quinupristin-dalfopristin 1. The recommended treatment duration for VRE infections with daptomycin varies depending on the infection site and clinical response, but typically ranges from 7-14 days for uncomplicated infections to 4-6 weeks for endocarditis or bone infections 1. It is also important to note that daptomycin should be used cautiously in patients with renal impairment and that creatine phosphokinase (CPK) levels should be monitored weekly to watch for potential muscle toxicity 1.

Some key points to consider when using daptomycin to treat VRE infections include:

• Daptomycin is not effective for respiratory infections as it is inactivated by lung surfactant, so alternative agents should be considered for VRE pneumonia
• Combination therapy with beta-lactams may be considered in VRE bloodstream infections with high daptomycin MIC (3-4 mg/mL)
• Tigecycline, fosfomycin, and nitrofurantoin are alternative treatment options for VRE infections, particularly for uncomplicated urinary tract infections
• High-dose ampicillin or amoxicillin may be recommended for uncomplicated urinary tract infections due to VRE

Overall, daptomycin is a valuable treatment option for VRE infections, particularly for serious infections like bacteremia or endocarditis, and should be used in accordance with recommended guidelines and dosing regimens.

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[see Indications and Usage (1)] Gram-Positive Bacteria Enterococcus faecalis (vancomycin-susceptible isolates only) ... The following in vitro data are available, but their clinical significance is unknown At least 90 percent of the following bacteria exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for daptomycin against isolates of similar genus or organism group. However, the efficacy of daptomycin in treating clinical infections caused by these bacteria has not been established in adequate and well-controlled clinical trials Gram-Positive Bacteria ... Enterococcus faecium (including vancomycin-resistant isolates)

Daptomycin is effective in vitro against Vancomycin-Resistant Enterococcus (VRE), including Enterococcus faecium (vancomycin-resistant isolates). However, the clinical efficacy of daptomycin in treating infections caused by VRE has not been established in adequate and well-controlled clinical trials 2.

• Key points:
  • In vitro activity: Daptomycin has been shown to be active against VRE.
  • Clinical efficacy: Not established in adequate and well-controlled clinical trials.

From the Research

Effectiveness of Daptomycin Against VRE

• Daptomycin is effective against Vancomycin-Resistant Enterococcus (VRE), with studies showing its efficacy in treating VRE bloodstream infections 3, 4, 5, 6, 7.
• The optimal dose of daptomycin for treating VRE is still being determined, but higher doses (≥9 mg/kg) have been associated with better outcomes and lower mortality rates 3, 4, 7.
• Daptomycin has been shown to be more active against VRE than other antibiotics, such as vancomycin and linezolid, in some studies 5, 6.
• However, the efficacy of daptomycin can be influenced by the minimum inhibitory concentration (MIC) of the VRE isolate, with higher MICs potentially requiring higher doses of daptomycin 7.

Key Findings

• A study published in 2017 found that higher daptomycin doses (≥9 mg/kg) were associated with lower mortality rates in patients with VRE bloodstream infections 3.
• Another study published in 2016 found that higher-dose daptomycin (≥9 mg/kg) was associated with better survival rates than lower-dose daptomycin (6-9 mg/kg) 4.
• A review of pharmacotherapy options for resistant enterococcal infections published in 2018 noted that daptomycin and linezolid have demonstrated clinical efficacy against VRE 6.
• A study published in 2022 found that increasing the daptomycin dose to ≥11 mg/kg improved survival in patients with VRE bloodstream infections, but was associated with a higher rate of highly elevated creatine kinase 7.