What are the clinical and microbiological differences between Enterococcus (E.) faecium and Enterococcus (E.) faecalis, particularly in terms of antibiotic resistance and treatment options, in elderly, immunocompromised, or medically complex patients?

Clinical and Microbiological Differences Between E. faecium and E. faecalis

The most critical distinction is that E. faecium exhibits intrinsic penicillin resistance and up to 95% multidrug resistance, while E. faecalis remains largely ampicillin-susceptible with only 3% multidrug resistance, fundamentally altering treatment approaches. 1, 2

Antibiotic Resistance Patterns

E. faecalis Resistance Profile

• Ampicillin remains the gold standard with most strains retaining susceptibility (only 19.6% resistance in surveillance data) 2, 3, 4
• Vancomycin resistance is rare, occurring in approximately 3% of strains 1, 2
• When vancomycin-resistant E. faecalis does occur, many strains paradoxically remain penicillin-susceptible 1
• High-level aminoglycoside resistance is increasingly common but less prevalent than in E. faecium 1

E. faecium Resistance Profile

• Intrinsic penicillin resistance is the hallmark, making ampicillin ineffective as first-line therapy 1, 2, 5
• Up to 95% of strains express multidrug resistance to vancomycin, aminoglycosides, and penicillins 1, 2
• Ampicillin resistance reaches 50.9-69.1% in clinical isolates 6, 4
• The majority of vancomycin-resistant enterococcus (VRE) infections are attributed to E. faecium 1
• Hospital-adapted clonal complex CC17 strains drive the increasing prevalence of resistant E. faecium 5

Virulence Factor Differences

E. faecalis Virulence Profile

• Harbors a significantly broader spectrum of virulence determinants compared to E. faecium 6, 7
• Beta-hemolysis occurs in 51% of E. faecalis versus only 1.6% of E. faecium (p<0.001) 6
• Gelatinase activity present in 28.6% of E. faecalis versus 3.3% of E. faecium (p<0.001) 6
• Higher prevalence of virulence genes: cylA, asa1, gelE, sprE, fsrA, fsrB, fsrC, ace, ebp, and efa 6, 7
• The esp gene is more prevalent in clinical E. faecalis isolates (67.8%) compared to environmental strains 7

E. faecium Virulence Profile

• Only the hyl gene and biofilm production occur more frequently in E. faecium than E. faecalis 6
• Biofilm formation occurs in 11.5% of E. faecium versus 8.2% of E. faecalis (not statistically significant) 6
• Generally possesses fewer well-defined virulence factors despite causing serious infections 6

Microbiological Identification

Laboratory Differentiation

• Both species are PYR-positive and share colonial morphology on primary isolation plates 1
• Motility testing is the key differentiator: E. faecium is nonmotile and nonpigmented, while E. gallinarum and E. casseliflavus are motile 1
• Species-level identification helps predict resistance patterns but is not routinely necessary if antimicrobial susceptibility testing is performed 1
• Commercial identification systems adequately differentiate E. faecalis from other enterococcal species 1

Treatment Implications for Elderly and Immunocompromised Patients

E. faecalis Treatment Algorithm

• First-line: Ampicillin 2g IV every 4-6 hours for susceptible strains 2, 3
• For serious infections requiring bactericidal activity, combine ampicillin with gentamicin for synergy 2, 3
• Native valve endocarditis: 4-6 weeks of combination therapy 1, 2, 3
• Prosthetic valve endocarditis: minimum 6 weeks of treatment 1, 2
• For high-level aminoglycoside resistance, use double β-lactam regimen (ampicillin plus ceftriaxone) with comparable efficacy and less nephrotoxicity 2, 3
• Vancomycin 30 mg/kg/24h IV in 2 divided doses only for documented β-lactam allergy 1, 2, 3

E. faecium Treatment Algorithm

• First-line: Linezolid 600mg IV/PO every 12 hours for vancomycin-resistant strains 1, 2
• Alternative: Daptomycin 8-12 mg/kg/day IV for serious infections 1, 2, 3
• Tigecycline is appropriate for polymicrobial intra-abdominal infections 1
• Quinupristin-dalfopristin inhibits only E. faecium (not E. faecalis) but is rarely used due to severe side effects including intractable muscle pain 1

Clinical Context Differences

Hospital-Acquired vs. Community-Acquired

• E. faecalis and E. faecium are more prevalent in hospital-acquired intra-abdominal infections (22.3%) versus community-acquired (13.9%) 1
• Empirical enterococcal coverage is not generally recommended for community-acquired infections 1
• Always consider enterococcal coverage in postoperative or tertiary peritonitis, particularly in elderly and immunocompromised patients 1

Risk Factors for VRE (Predominantly E. faecium)

• Previous antibiotic therapy, prolonged hospitalization, ICU admission 1
• Severe underlying illness, invasive procedures, gastrointestinal surgery 1
• Organ transplantation and close proximity to VRE-positive patients 1

Critical Pitfalls to Avoid

• Never assume E. faecium has the same susceptibility profile as E. faecalis – they require fundamentally different empiric coverage 2, 3
• Never use cephalosporins alone for enterococcal coverage – they have no intrinsic activity despite potential in vitro synergy 2
• Do not prescribe vancomycin empirically for E. faecalis when ampicillin is superior and available 2, 3
• Always obtain infectious disease consultation for enterococcal endocarditis as standard of care 2
• Differentiate colonization from true infection before initiating anti-enterococcal therapy 3
• Fully automated methods for testing vancomycin resistance are unreliable and require confirmation 1

Epidemiological Trends

• The worldwide ratio of E. faecalis to E. faecium infections is shifting toward E. faecium due to antimicrobial resistance and hospital-adapted strains 5
• E. faecium now represents a growing proportion of enterococcal infections in healthcare settings 5
• Multidrug resistance is significantly more prevalent in clinical isolates (71.2% E. faecalis, 70.3% E. faecium) compared to environmental isolates 7