What is the management of Vancomycin-Resistant Enterococci (VRE)?

From the Guidelines

Vancomycin-resistant Enterococcus (VRE) management should prioritize linezolid (600mg IV/PO twice daily) as the first-line treatment option, given its strong recommendation and low quality of evidence as per the latest guidelines 1.

Treatment Options

The treatment of VRE infections depends on the site and severity of the infection.

• For pneumonia, linezolid 600 mg IV q12 h is recommended for at least 7 days 1.
• For bloodstream infections, linezolid 600 mg IV q12 h or daptomycin 8-12 mg/kg IV qd in combination with beta-lactams may be considered, with a treatment duration of 10-14 days 1.
• For complicated intra-abdominal infections, linezolid 600 mg IV q12 h or tigecycline 50 mg IV q12 h after a loading dose of 100 mg IV may be used, with a treatment duration of 5-7 days 1.
• For uncomplicated urinary tract infections, fosfomycin 3 g PO x 1 dose, nitrofurantoin 100 mg PO qid, or ampicillin 18-30 g/day IV in divided doses may be considered, with a treatment duration of 3-7 days 1.

Infection Control Measures

In addition to antimicrobial therapy, infection control measures are crucial in preventing the transmission of VRE in healthcare settings.

• Contact precautions with gloves and gowns should be implemented for patients with VRE infections.
• Dedicated patient equipment and proper hand hygiene with alcohol-based sanitizers are essential.
• Environmental cleaning with hospital-grade disinfectants and antibiotic stewardship to limit unnecessary vancomycin use are also important.
• Patient isolation should continue until negative surveillance cultures (typically rectal swabs) are obtained on at least two occasions one week apart.

Challenges in VRE Management

VRE management is challenging due to the development of resistance to glycopeptide antibiotics through altered cell wall precursors (VanA or VanB genes), limiting treatment options and necessitating strict infection control measures to prevent transmission in healthcare settings 1.

From the FDA Drug Label

CLINICAL STUDIES Adults Vancomycin-Resistant Enterococcal Infections Adult patients with documented or suspected vancomycin-resistant enterococcal infection were enrolled in a randomized, multi-center, double-blind trial comparing a high dose of ZYVOX (600 mg) with a low dose of ZYVOX (200 mg) given every 12 hours (q12h) either intravenously (IV) or orally for 7 to 28 days The cure rates for the ITT population with documented vancomycin-resistant enterococcal infection at baseline are presented in Table 15 by source of infection. Table 15. Cure Rates at the Test-of-Cure Visit for ITT Adult Patients with Documented Vancomycin-Resistant Enterococcal Infections at Baseline Source of InfectionCured ZYVOX600 mg q12hn/N (%)ZYVOX200 mg q12hn/N (%) Any site39/58 (67)24/46 (52) Any site with associated bacteremia10/17 (59)4/14 (29) Bacteremia of unknown origin5/10 (50)2/7 (29) Skin and skin structure9/13 (69)5/5 (100) Urinary tract12/19 (63)12/20 (60) Pneumonia 2/3 (67)0/1 (0) Other*11/13 (85)5/13 (39)

The management of Vancomycin-Resistant Enterococcal (VRE) infections can be achieved with linezolid (ZYVOX).

• The cure rates for VRE infections were higher in the high-dose arm (600 mg) than in the low-dose arm (200 mg), although the difference was not statistically significant at the 0.05 level.
• The cure rates ranged from 39% to 85% depending on the source of infection.
• Linezolid can be used to treat VRE infections, including those with associated bacteremia.
• The cure rates for VRE infections with bacteremia of unknown origin were 50% in the high-dose arm and 29% in the low-dose arm.
• Linezolid can be administered orally or intravenously for the treatment of VRE infections 2.
• In pediatric patients, linezolid was effective in treating VRE infections, with a cure rate of 75% in microbiologically evaluable patients 2.

From the Research

VRE Management Overview

• Vancomycin-resistant enterococcal (VRE) infections are a significant concern, particularly in patients with compromised host defenses and serious co-morbidities 3.
• Effective antimicrobial treatment is crucial, and various options are available, including quinupristin/dalfopristin, linezolid, daptomycin, and tigecycline 3, 4, 5, 6.

Treatment Options

• Quinupristin/dalfopristin is a streptogramin that impairs bacterial protein synthesis and has bacteriostatic activity against vancomycin-resistant E. faecium, but not against E. faecalis 3.
• Linezolid is an oxazolidinone compound that inhibits bacterial pre-translational initiation complex formation and has bacteriostatic activity against both vancomycin-resistant E. faecium and E. faecalis 3.
• Daptomycin is a lipopeptide antibiotic that has been shown to be effective against VRE, particularly in combination with β-lactams 5.
• Tedizolid is a second-generation oxazolidinone that has activity against some linezolid-resistant VRE strains, but its effectiveness is limited by the predominant resistance mechanism 7.

Comparative Studies

• A study comparing linezolid and daptomycin for the treatment of VRE bloodstream infections found that daptomycin was associated with a lower risk of treatment failure and 30-day mortality 4.
• Another study found that tigecycline generally showed the greatest activity against VRE, but resistance was still observed in some strains 6.

Novel Strategies

• Fecal microbiota transplantation (FMT) has shown promise in treating colonization and infection due to VRE, as well as recovering the integrity of the gut microbiota under antibiotic pressure 5.
• The use of bacteriophages may also be a promising strategy in eradicating VRE from the gut of patients 5.
• Infection control measures and stewardship programs are essential for controlling the spread of VRE and reducing the risk of infection 5.