Vancomycin-Resistant Enterococci: Symptoms, Types, Causes and Treatment

Vancomycin-resistant enterococci (VRE) have rapidly emerged as some of the most concerning pathogens in healthcare settings worldwide. Their rise is linked to both increased antibiotic resistance and the unique challenges they present in hospitals, especially among vulnerable patient populations. In this article, we delve into the key aspects of VRE—its symptoms, types, causes, and treatment—offering a clear, evidence-based overview for healthcare professionals, patients, and anyone concerned about the spread of antibiotic-resistant infections.

Symptoms of Vancomycin-Resistant Enterococci

Vancomycin-resistant enterococci can cause a range of symptoms depending on the location and severity of the infection. While some individuals may be asymptomatically colonized, others—particularly those with weakened immune systems—may experience serious, sometimes life-threatening infections.

Symptom Area	Common Presentations	Affected Populations	Source(s)
Bloodstream	Fever, chills, sepsis	Immunocompromised, hospital patients	1, 7, 13
Urinary Tract	Dysuria, frequency, urgency	Hospitalized patients, elderly	1, 5, 7
Heart	Endocarditis (fever, murmur, emboli)	Pre-existing heart disease	1, 2, 7
Abdomen/Pelvis	Pain, peritonitis, abscess	Post-surgical, ICU patients	1, 7
Skin/Wounds	Redness, swelling, discharge	Surgical/trauma patients	1, 7

Table 1: Key Symptoms

Overview of VRE Symptomatology

VRE infections present with a broad spectrum of symptoms, often mimicking those caused by other bacteria. The severity and type of symptoms are intimately tied to the site of infection and the patient's underlying health.

Bloodstream Infections (Bacteremia & Sepsis)

• Symptoms: Fevers, chills, low blood pressure, and signs of sepsis are common in VRE bloodstream infections. These are more frequent in patients with weakened immune systems, recent surgery, or indwelling medical devices 1, 7, 13.
• Risk: This is one of the most severe forms, often associated with high mortality rates if not promptly treated.

Urinary Tract Infections (UTIs)

• Symptoms: Burning sensation during urination, increased frequency, urgency, lower abdominal pain, and sometimes fever 1, 5, 7.
• Populations at Risk: Hospitalized individuals, especially those with urinary catheters or underlying urological conditions.

Endocarditis

• Symptoms: Persistent fever, heart murmur, and signs of heart failure or embolic events (e.g., stroke, kidney infarcts) 1, 2, 7.
• Who Gets It: Patients with pre-existing heart valve disease or prosthetic heart valves are particularly at risk.

Intra-abdominal and Pelvic Infections

• Symptoms: Localized abdominal pain, fever, peritonitis, abscess formation 1, 7.
• Common Scenarios: Often occur after abdominal or pelvic surgery or in critically ill patients.

Skin and Wound Infections

• Symptoms: Redness, swelling, pus, and delayed wound healing 1, 7.
• Risk Factors: Mostly seen in patients with surgical wounds, trauma, or chronic ulcers.

Colonization Without Symptoms

• Many people, particularly in hospital settings, may carry VRE in their gastrointestinal tract without symptoms. While colonization itself does not cause illness, it can lead to infection, especially if the patient becomes immunosuppressed or undergoes invasive procedures 13.

Types of Vancomycin-Resistant Enterococci

Understanding the types of VRE helps clarify why some infections are more difficult to treat and control than others. The diversity among enterococci and their resistance mechanisms is central to their clinical importance.

VRE Type/Species	Main Resistance Genes	Clinical Relevance	Source(s)
E. faecium	vanA, vanB	Most common VRE in hospitals, high resistance	2, 3, 4, 5, 11
E. faecalis	Rarely vanA/vanB	Less common, still clinically important	2, 4, 5, 11
E. gallinarum	vanC (intrinsic)	Mild, hospital-acquired infections	6
E. casseliflavus	vanC (intrinsic)	Less frequent, mainly in at-risk patients	6
Other Enterococcus spp.	Occasionally vanD, vanE, vanG	Rare, clinical impact not well defined	3, 4, 6

Table 2: Major Types of VRE

Species Overview

Enterococcus faecium

• Dominant VRE species globally; responsible for the vast majority of hospital outbreaks and severe infections.
• Resistance genes: Most often carries vanA and, less commonly, vanB, both of which can be transferred between bacteria via mobile genetic elements 3, 4, 5, 11.
• Clinical Impact: High-level resistance, frequent multi-drug resistance, making treatment challenging.

Enterococcus faecalis

• Less frequently resistant: While E. faecalis is a common enterococcal species causing infections, vancomycin resistance is much rarer compared to E. faecium 2, 4, 5, 11.
• Clinical Role: Still important, as it can cause severe infections, particularly in the urinary tract and heart.

Enterococcus gallinarum and E. casseliflavus

• Intrinsic resistance: These species possess the vanC gene naturally (intrinsic resistance), which results in low-level vancomycin resistance 6.
• Clinical Relevance: Cause mainly healthcare-associated infections, particularly in immunocompromised patients or those with hepatobiliary disease. Their resistance is chromosomally encoded and not easily transferred to other bacteria, posing different infection control challenges.

Less Common Genotypes (vanD, vanE, vanG)

• Rare: These resistance types are infrequent and their clinical impact is not fully understood, but their presence reinforces the genetic diversity of VRE 3, 4, 6.

Resistance Mechanisms

• Acquired resistance (vanA, vanB): Often associated with mobile genetic elements, allowing for rapid spread within hospitals 3, 4.
• Intrinsic resistance (vanC): Chromosomally encoded, not transferred between species, associated with E. gallinarum and E. casseliflavus 6.

Causes of Vancomycin-Resistant Enterococci

The emergence and spread of VRE are rooted in both microbial evolution and human healthcare practices. Understanding these causes is crucial for both prevention and control.

Cause	Mechanism/Description	Key Populations/Settings	Source(s)
Antibiotic Overuse	Selects for resistant strains, especially vancomycin and broad-spectrum antibiotics	Hospitalized, ICU patients	1, 2, 12, 13
Horizontal Gene Transfer	Movement of van genes (vanA/vanB) via plasmids/transposons	Hospital environments	3, 4, 7
Prolonged Hospitalization	Increases exposure risk, especially with invasive devices	ICU, oncology, transplant	1, 2, 8, 11
Colonization Pressure	High-density VRE colonization promotes transmission	Units with many colonized patients	12, 13
Animal Reservoirs	VRE found in food animals, potential zoonotic source	Community, food supply	4

Table 3: Main Causes and Risk Factors

Antibiotic Pressure and Selection

• Overuse of Vancomycin & Broad-Spectrum Antibiotics: Frequent or prolonged use of vancomycin and agents active against anaerobes (such as certain cephalosporins and carbapenems) can eliminate competing gut bacteria, allowing VRE to flourish 1, 12.
• Antianaerobic Therapy: Especially promotes high-density colonization, increasing risk of transmission and infection 12.

Genetic Transmission

• Mobile Genetic Elements: The vanA and vanB genes are typically carried on plasmids and transposons, facilitating their spread between bacteria in hospital settings 3, 4, 7.
• Rapid Adaptation: Enterococci are highly adaptable, with "genome plasticity" that lets them acquire new resistance traits 1, 3.

Hospital Environment and Patient Factors

• Prolonged Hospitalization & ICU Stay: The longer a patient stays in high-risk units, the greater the chance of acquiring VRE, especially when invasive devices (catheters, central lines) are present 1, 2, 8, 11.
• Colonization Pressure: When many patients in a unit are colonized, risk for new cases rises, especially if infection control lapses occur 12, 13.

Community and Animal Sources

• Food and Animal Reservoirs: VRE strains, especially E. faecium, have been isolated from meat and eggs, raising concerns about zoonotic transfer and the food chain as a reservoir of resistance genes 4.

Additional Risk Factors

• Immunosuppression: Patients with cancer, transplant recipients, or those with chronic illnesses are at much higher risk for VRE infection following colonization 1, 13.
• Healthcare Worker Transmission: VRE can survive on surfaces for long periods and be transferred by hands, clothing, or equipment if proper hygiene is not maintained 13.

Treatment of Vancomycin-Resistant Enterococci

Treating VRE infections is a significant challenge due to their resistance to vancomycin and often to multiple other antibiotics. However, new therapies and rigorous infection control offer hope in combating these formidable pathogens.

Drug/Class	Efficacy Against VRE	Issues/Limitations	Source(s)
Linezolid	Good	Hematologic side effects, resistance emerging	1, 13, 14
Daptomycin	Good (high dose)	Not always bactericidal, high dose needed	1, 14
Quinupristin-dalfopristin	Effective (E. faecium)	Not active vs E. faecalis, side effects	1, 13, 14
Tigecycline	Variable	Bacteriostatic, not for bloodstream infections	1, 14
Newer Agents (tedizolid, oritavancin, dalbavancin)	Promising	Limited data, not fully established	1
Decolonization (niclosamide)	Experimental	Not yet standard of care	15
Source Control & Infection Prevention	Critical	Must be combined with antibiotics	1, 13

Table 4: Therapeutic Options and Strategies

Mainstay Treatments

Linezolid

• Activity: Highly active against most VRE strains 1, 13, 14.
• Limitations: Prolonged use can cause bone marrow suppression and neuropathy. Resistance is increasing in some regions 14.
• Role: Often first-line, especially for bloodstream and deep tissue infections.

Daptomycin

• Activity: Effective at high doses; bactericidal against enterococci 1, 14.
• Limitations: Must be dosed higher for enterococcal infections than for other bacteria. Not effective in pneumonia as it is inactivated by lung surfactant.

Quinupristin-dalfopristin

• Activity: Active against E. faecium but not E. faecalis 1, 13, 14.
• Side Effects: Can cause joint and muscle pain, and infusion-related reactions.

Tigecycline

• Activity: Broad-spectrum, including VRE 1, 14.
• Limitations: Bacteriostatic rather than bactericidal; not effective for bloodstream infections.

Newer and Experimental Agents

• Tedizolid, dalbavancin, oritavancin: Early evidence suggests potential, but clinical experience is limited 1.
• Niclosamide: An anti-parasitic drug recently shown to reduce VRE colonization in animal models, potentially useful for decolonization, especially in the gut 15.

Other Management Strategies

Source Control

• Essential for Cure: Removing infected catheters, draining abscesses, and correcting underlying anatomical issues are vital steps 1.

Infection Control Measures

• Isolation and Hygiene: Rigorous hand hygiene, environmental cleaning, and isolation of colonized or infected patients help prevent spread 13.
• Antibiotic Stewardship: Limiting unnecessary antibiotic use reduces selection pressure for resistance 1, 12.

Challenges and Future Directions

• Resistance to Last-Resort Drugs: Emergence of VRE strains resistant to linezolid, daptomycin, and tigecycline is a growing concern 14.
• Therapy Individualization: Due to differences in species, resistance genes, and site of infection, treatment must be tailored to each case 1, 6.
• Decolonization: While not standard, new agents like niclosamide show promise in reducing gastrointestinal carriage of VRE in high-risk patients 15.

Conclusion

Vancomycin-resistant enterococci represent a formidable challenge in modern medicine, particularly in hospitals and among vulnerable patients. Their ability to survive, adapt, and resist multiple antibiotics underscores the need for vigilant detection, prevention, and individualized therapy.

Key Takeaways:

• Symptoms range from asymptomatic colonization to life-threatening sepsis, with presentation depending on infection site and patient vulnerability 1, 7, 13.
• Major Types include E. faecium (most common and resistant), E. faecalis (less frequently resistant), and intrinsically resistant species like E. gallinarum 2, 3, 4, 5, 6, 11.
• Causes are rooted in antibiotic overuse, genetic adaptability, prolonged hospitalization, and even animal reservoirs 1, 2, 3, 4, 7, 12, 13.
• Treatment relies on newer antibiotics (linezolid, daptomycin), rigorous source control, and strict infection prevention, with emerging therapies and decolonization strategies on the horizon 1, 13, 14, 15.

A multifaceted approach—combining prudent antibiotic use, robust infection control, and ongoing research—is essential to curb the spread and impact of vancomycin-resistant enterococci in the years to come.