What is the recommended treatment for serious infections caused by gram-positive bacteria, such as Methicillin-Resistant Staphylococcus aureus (MRSA) and Vancomycin-Resistant Enterococcus (VRE)?

From the Guidelines

For serious infections caused by gram-positive bacteria like MRSA and VRE, the most recent and highest quality study recommends linezolid (600 mg IV/oral twice daily) or high-dose daptomycin (8-12 mg/kg IV daily) as the preferred options for VRE infections, as these bacteria are resistant to vancomycin 1.

Treatment Options

• Vancomycin is typically the first-line treatment for MRSA infections, administered intravenously at 15-20 mg/kg every 8-12 hours, with target trough levels of 15-20 μg/mL for severe infections.
• For VRE infections, linezolid (600 mg IV/oral twice daily) or high-dose daptomycin (8-12 mg/kg IV daily) are preferred options.
• Alternative medications for both pathogens include tigecycline, telavancin, and newer agents like tedizolid.

Treatment Duration

• Treatment duration typically ranges from 7-14 days but may extend to 4-6 weeks for complicated infections like endocarditis or osteomyelitis.
• Source control through drainage of abscesses or removal of infected devices is crucial for successful treatment.

Monitoring

• Regular monitoring of kidney function is necessary during vancomycin therapy.
• Linezolid requires blood count monitoring due to potential bone marrow suppression with prolonged use.

Recent Guidelines

• The most recent guidelines recommend high-dose daptomycin at 8-12 mg/kg daily for the treatment of VRE bacteremia 1.
• Combination antimicrobial therapy may be considered in severely ill patients or those who fail treatment with traditional options 1.

From the FDA Drug Label

Daptomycin for injection is indicated for the treatment of adult and pediatric patients (1 to 17 years of age) with complicated skin and skin structure infections (cSSSI) caused by susceptible isolates of the following Gram-positive bacteria: Staphylococcus aureus (including methicillin-resistant isolates), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus dysgalactiae subsp. equisimilis, and Enterococcus faecalis (vancomycin-susceptible isolates only). Daptomycin for injection is indicated for the treatment of adult patients with Staphylococcus aureus bloodstream infections (bacteremia), including adult patients with right-sided infective endocarditis, caused by methicillin-susceptible and methicillin-resistant isolates. Vancomycin Hydrochloride for Injection, USP is indicated for the treatment of serious or severe infections caused by susceptible strains of methicillin-resistant (β-lactam-resistant) staphylococci

The recommended treatment for serious infections caused by gram-positive bacteria, such as Methicillin-Resistant Staphylococcus aureus (MRSA) and Vancomycin-Resistant Enterococcus (VRE), includes:

• Daptomycin for complicated skin and skin structure infections and bloodstream infections, including right-sided infective endocarditis, caused by MRSA [ 2 ].
• Vancomycin for the treatment of serious or severe infections caused by susceptible strains of methicillin-resistant staphylococci [ 3 ]. Note that Vancomycin is not effective against Vancomycin-Resistant Enterococcus (VRE).

From the Research

Treatment of Serious Infections Caused by Gram-Positive Bacteria

The recommended treatment for serious infections caused by gram-positive bacteria, such as Methicillin-Resistant Staphylococcus aureus (MRSA) and Vancomycin-Resistant Enterococcus (VRE), includes the use of lipopeptide antibiotics.

• Daptomycin, a lipopeptide antimicrobial, has been shown to have in vitro bactericidal activity against Gram-positive bacteria, including MRSA and VRE 4, 5, 6, 7, 8.
• It has a unique mechanism of action, disrupting the cell membrane and causing the dissipation of the membrane potential 5, 6, 8.
• Daptomycin has been approved for the treatment of complicated skin and skin structure infections, as well as for the treatment of S. aureus bacteremia and right-sided endocarditis 5, 6.

Efficacy and Safety of Daptomycin

• Daptomycin has been found to be effective in treating various serious Gram-positive infections, including those caused by MRSA 6, 7.
• It has a prolonged postantibiotic effect and is well tolerated, with a low potential for resistance 5, 6, 7.
• The incidence and nature of serious adverse events associated with daptomycin are comparable to those observed with conventional therapy 7.
• Daptomycin is not indicated for pulmonary infections, but preliminary data suggest that it may be effective in urinary tract, bone, and joint infections 6.

Mechanisms of Nonsusceptibility

• Nonsusceptibility to daptomycin can occur, particularly in the context of prolonged treatment courses and infections with high bacterial burdens 4.
• Mechanisms of nonsusceptibility in S. aureus and Enterococcus are mediated by adaptations to cell wall homeostasis and membrane phospholipid metabolism 4.