Enterococcal Infections¶
Chapter 154 | Part 5: Infectious Diseases · Part 5 – Infectious Diseases: Bacterial · Chapter 154
Key Clinical Points¶
- Enterococci are the third most common hospital-associated infection isolates in the US, following E. coli and staphylococci.
- E. faecium is highly resistant; >90% of isolates are ampicillin-resistant, with vancomycin resistance (VRE) ranging from 50–70% in acute care hospitals to up to 80% in long-term care facilities.
- Synergistic bactericidal activity is achieved by combining a cell-wall active agent (β-lactam or glycopeptide) with an aminoglycoside (gentamicin or streptomycin).
- Linezolid is the only FDA-approved agent for VRE infections but is non-bactericidal and carries risks of thrombocytopenia, peripheral neuropathy, and optic neuritis.
- Daptomycin is bactericidal against all enterococci; however, E. faecium with MIC ≤ 4 mg/L requires high-dose regimens (8–12 mg/kg).
- Enterococcal endocarditis is typically subacute; valve replacement may be critical for infections caused by multidrug-resistant organisms.
- VRE colonization of the GI tract is a critical step in disease development; patients can remain colonized for >1 year.
- Cephalosporins are not active as monotherapy against enterococci; ampicillin and amoxicillin are the most active β-lactams.
- Intraabdominal infections in hospitalized patients are increasingly caused by vancomycin-resistant E. faecium, leading to treatment failures.
- Enterococcal meningitis is rare (~4% of cases) and associated with neurosurgical interventions or hematogenous seeding from endocarditis.
1. DEFINITION & OVERVIEW¶
Enterococci are gram-positive organisms observed as single cells, diplococci, or short chains in clinical specimens.
1.1 Microbiology and Taxonomy¶
• Morphology: Gram-positive cocci; appear as single cells, diplococci, or short chains. • Classification: Distinct from streptococci based on DNA hybridization studies and 16S rRNA sequencing. • Metabolic Characteristics: ◦ Hydrolyze esculin in the presence of 40% bile salts ◦ Grow at high salt concentrations (e.g., 6.5%) ◦ Grow at high temperatures (46°C) • Hemolysis: Usually nonhemolytic; however, some E. faecalis strains possess an acquired hemolysin/cytolysin gene allowing them to lyse RBCs from humans, horses, and rabbits. • Biochemical Markers: The majority of clinically relevant species hydrolyze pyrrolidonyl-β-naphthylamide (PYR).
2. EPIDEMIOLOGY¶
Enterococci are the third most common isolates from hospital-associated infections in the US, after E. coli and staphylococci.
2.1 Prevalence and Resistance¶
• Species Trends: E. faecalis is the predominant species; however, E. faecium isolation has increased significantly over the past 20 years (now ~1/3 of all enterococcal infections). • Resistance Profiles: ◦ E. faecium: >90% are ampicillin-resistant. ◦ Vancomycin Resistance (VRE): 50–70% in acute care hospitals; up to 80% in long-term care facilities. • Genomic Clades: ◦ Clade A: Hospital-associated, rapidly evolving, drug-resistant; lacks functional CRISPR-Cas systems; possesses PBP5 alleles associated with β-lactam resistance. ◦ Clade B: Community-associated, susceptible phenotype.
2.2 Risk Factors for VRE Colonization¶
• Clinical Factors: Prolonged hospitalization, long antibiotic courses, ICU/surgical unit admission, organ transplantation, renal failure (especially hemodialysis), diabetes, and high APACHE scores. ◦ Environmental Factor: Proximity to VRE-colonized patients.
3. ETIOLOGY & PATHOPHYSIOLOGY¶
Enterococci are normal inhabitants of the human gastrointestinal tract (<1% of intestinal microbiota).
3.1 Colonization Dynamics¶
• Colonization Resistance: Enterococci may contribute to resistance against drug-resistant pathogens like VRE. ◦ Disruption Factors: Proton pump inhibitors (reducing gastric pH), mucin layer degradation, and antibiotic use. ◦ Nutrient Dynamics: Fructose depletion by Olsenella reduces VRE; lactose promotes enterococcal growth. • Pathogenic Interactions: ◦ Enhance C. difficile virulence by altering amino acid availability and arginine depletion. ◦ Bacteriocins from E. faecalis plasmids enhance competitive fitness. • Clearance: VRE clearance post-discharge takes 2–4 months in patients without ongoing risk factors.
3.2 Resistance Mechanisms¶
• Tolerance: Defined as lack of killing by drug concentrations 32 imes MIC. • Synergistic Activity: Combination of a cell-wall active agent (β-lactam or glycopeptide) and an aminoglycoside (gentamicin or streptomycin) → enhanced aminoglycoside penetration due to cell-wall alterations by β-lactams. ◦ Note: Resistance to all available antibiotics makes achieving this synergy increasingly difficult, especially for E. faecium.
4. CLINICAL FEATURES¶
Enterococci are leading causes of nosocomial infections, particularly in the urinary tract.
4.1 Clinical Syndromes¶
• Urinary Tract Infections (UTI): Most common; often associated with indwelling catheters or genitourinary instrumentation. ◦ Diagnosis: Challenging to differentiate infection from colonization in catheterized patients. ◦ Presentation: Fever, leukocytes in urine, and positive cultures (>10⁵ CFU/mL). • Bacteremia: Second most common cause of central line-associated bacteremia after staphylococci; often linked to intravascular devices. ◦ Complications: May be polymicrobial or linked to Strongyloides stercoralis hyperinfection in immunocompromised patients. • Endocarditis: Second only to staphylococci; typically subacute with fever, weight loss, and cardiac murmur. ◦ Risk: E. faecium associated with worse outcomes due to higher resistance rates. ◦ Intervention: Valve replacement may be critical for multidrug-resistant infections. • Meningitis: Rare (~4% of cases); linked to neurosurgical interventions or hematogenous seeding from endocarditis.
5. DIFFERENTIAL DIAGNOSIS¶
Enterococcal infections must be differentiated from other gram-positive organisms (staphylococci, streptococci) and polymicrobial infections.
5.1 Colonization vs. Infection¶
• Colonization: Asymptomatic with positive cultures. • Infection: Symptomatic (e.g., fever, leukocytosis) with positive cultures and clinical signs.
6. INVESTIGATIONS & DIAGNOSIS¶
Diagnosis relies on culture of blood, urine, or other body fluids.
6.1 Diagnostic Criteria¶
- Blood Cultures: Positive for enterococci.
- Urine Culture: ≥10⁵ CFU/mL with symptoms.
- Molecular Testing: PCR to detect vancomycin resistance genes (vanA/vanB).
- Echocardiography: Critical for identifying vegetations or valve abnormalities in endocarditis.
- CSF Analysis: Evaluation of pleocytosis, elevated protein, and low glucose in suspected meningitis.
7. MANAGEMENT & TREATMENT¶
Treatment depends on infection type and resistance profile.
7.1 Therapeutic Regimens¶
- Uncomplicated UTI: ◦ Ampicillin 2 g IV q4h ◦ Amoxicillin 500 mg PO q8h
- Endocarditis (E. faecalis): ◦ Option A: Ampicillin (12 g/d IV in divided doses q4h) + ceftriaxone (2 g IV q12h) ◦ Option B: Ampicillin (12 g/d IV q4h or continuous infusion) OR penicillin (18–30 mU/d IV q4h or continuous infusion) + an aminoglycoside ◦ Option C: Vancomycin (15 mg/kg IV per dose) + an aminoglycoside ◦ Option D: High-dose daptomycin ± another active agent ◦ Option E: Ampicillin + imipenem
- Endocarditis (VRE E. faecium): ◦ Option A: High-dose daptomycin + another agent ± an aminoglycoside ◦ Option B: Linezolid (600 mg IV q12h) ◦ Option C: High-dose ampicillin (if MIC ≤ 64 μg/mL) ± an aminoglycoside ◦ Note: Daptomycin for E. faecium with MIC ≤ 4 mg/L requires 8–12 mg/kg IV q24h.
- Meningitis: ◦ Option A (E. faecalis): Ampicillin (20–24 g/d IV q4h) or penicillin (24 mU/d IV q4h) + an aminoglycoside; consider adding ceftriaxone (2 g IV q12h) ◦ Option B: Vancomycin (500–750 mg IV q6h) + an aminoglycoside or rifampin ◦ Option C: Linezolid ◦ Option D: High-dose daptomycin (plus intraventricular daptomycin) ± another CSF-penetrating active agent.
8. PROGNOSIS & COMPLICATIONS¶
Prognosis depends on infection type and resistance profile.
8.1 Mortality and Relapse¶
• Endocarditis Mortality: ~20–30%; higher with E. faecium. • Relapse Rates (E. faecalis): ◦ Antibiotic therapy alone: 2–11% ◦ With surgery: 0–3%.
9. SPECIAL CONSIDERATIONS¶
Neonates and immunocompromised hosts require careful management.
9.1 Neonatal and Immunocompromised Hosts¶
• Neonates: Often present as sepsis or meningitis. • Immunocompromised: May present with atypical features (e.g., disseminated infection without fever).
10. KEY PEARLS & CLINICAL TRAPS¶
Key pearls include the importance of combination therapy for endocarditis and high resistance in E. faecium.
10.1 Board Exam Favorites¶
• Synergistic Therapy: β-lactam/glycopeptide + aminoglycoside for endocarditis. • VRE Prevalence: E. faecium 50–70% in acute care; up to 80% in long-term care. • Daptomycin Dosing: For E. faecium with MIC ≤ 4 mg/L, use 8–12 mg/kg IV q24h. • Clinical Trap: Avoid misdiagnosing colonization as infection in catheterized patients.
11. WHAT TO LOOK FOR — DIAGNOSTIC CLUES¶
Diagnostic clues include gram-positive cocci in chains on Gram stain, positive blood/urine cultures, and clinical signs of endocarditis.
11.1 Specific Findings¶
• Gram Stain: Gram-positive cocci in chains (Figure 154-1). • Endocarditis Signs: Fever, cardiac murmur, new regurgitant murmur. • Meningitis Markers: Pleocytosis, elevated protein, low glucose.
12. WHAT EXCLUDES THE DIAGNOSIS¶
Exclusion criteria include negative cultures and lack of clinical symptoms.
12.1 Exclusion Criteria¶
• Negative Cultures: Absence of growth from blood, urine, or CSF. • Asymptomatic Presentation: Lack of fever/leukocytosis (suggests colonization). • Alternative Diagnosis: Confirmed viral infection or other pathogens via imaging/testing.
Reference Tables¶
TABLE 154-1 Suggested Regimens for the Management of Infections Caused by Enterococcus faecalis¶
Harrison's 22e, p.1219
| CLINICAL SYNDROME |
SUGGESTED THERAPEUTIC OPTIONSa |
|---|---|
| Endovascular infections (including endocarditis) |
• Ampicillinb (12 g/d IV in divided doses q4h) plus ceftriaxone (2 g IV q12h) • Ampicillinb (12 g/d IV in divided doses q4h or by continuous infusion) or penicillin (18–30 mU/d IV in divided doses q4h or by continuous infusion) plus an aminoglycosidec • Vancomycind (15 mg/kg IV per dose) plus an aminoglycosidec • High-dose daptomycine ± another active agentf • Ampicillinb plus imipenem |
| Meningitis | • Ampicillin (20–24 g/d IV in divided doses q4h) or penicillin (24 mU/d IV in divided doses q4h) plus an aminoglycosidec,h and consider adding ceftriaxone (2 g IV q12h) • Vancomycin (500–750 mg IV q6h)d plus an aminoglycosidec or rifampin • Linezolid • High-dose daptomycine (plus intrathecal daptomycin) ± another active agentf |
TABLE 154-2 Suggested Regimens for the Management of Infections Caused by Vancomycin- and Ampicillin-Resistant…¶
Harrison's 22e, p.1220
| CLINICAL SYNDROME | SUGGESTED THERAPEUTIC OPTIONSa |
|---|---|
| Endovascular infections (including endocarditis) |
• High-dose daptomycinb plus another agentc ± an aminoglycosided • Linezolid (600 mg IV q12h) • High-dose ampicillin (if MIC is ≤64 μg/mL) ± an aminoglycosided |
| Meningitis | • Linezolid (600 mg IV q12h) ± another CSF-penetrating active agentf • High-dose daptomycinb (plus intraventricular daptomycin) ± another CSF-penetrating active agentf,g |