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Bacterial Endocarditis

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Bacterial Endocarditis, Infective Endocarditis, Infectious Endocarditis, Subacute Bacterial Endocarditis, Acute Endocarditis, Osler Node, Osler's Node, Janeway Lesion, Roth Spot, Roth's Spot

  • Epidemiology
  1. Incidence: 5-8 cases per 100,000 persons in U.S.
  2. Native valve affected in over 70-80% of cases
  3. Age
    1. Median age of onset: 58 years old
    2. Males older than 50 years are more commonly affected
    3. Increasing Incidence in those over age 65 years old
      1. Related to degenerative Heart Valve Disease and implanted devices
    4. Uncommon in children outside of specific risk factors (esp. Congenital Heart Disease, indwelling venous catheters)
  • Risk Factors
  1. Hemodialysis (7.9%)
    1. Chronic Intravenous Access
    2. Immunosuppression
    3. Calcific valvular heart disease
  2. IV Drug Abuse (9.8%)
    1. Less than 50% of endocarditis in IV Drug Abuse is associated with a pre-existing structural cardiac defect
    2. Higher risk with immunosuppression (e.g. HIV Infection)
    3. Staphylococcus aureus infection is most common
    4. Tricuspid valve endocarditis is nearly pathognomonic for IV Drug Abuse
      1. Tricuspid valve is rarely involved in other causes of Bacterial Endocarditis
      2. Larger bloodborne particulate matter in IVDA typically deposits on the tricuspid valve
      3. Smaller particulate matter (<10 um) may pass through lung capillaries and deposit on aortic valve or mitral valve
    5. Atypical presentation due to primarily right sided involvement
      1. No murmur typically heard
      2. Associated with septic pulmonary emboli
      3. Not associated with Splinter Hemorrhages or Conjunctival Hemorrhage
  3. Degenerative valvular disease (most common predisposing factor for native valve endocarditis)
    1. Mitral Regurgitation (43.4%)
    2. Aortic Regurgitation (26.3%)
    3. Rheumatic Heart Disease (3.3%)
  4. Hospitalization or long-term care stay (Nosocomial Infectious Endocarditis)
    1. Defined as endocarditis onset within 3-60 days of a health care facility admission
    2. Accounts for 20% of Infectious Endocarditis
    3. Typically associated with invasive procedures or Intravenous Access
  • Etiology
  • Predisposing lesion (60-80% of patients)
  1. Prosthetic Heart Valve
  2. Rheumatic Heart Disease (30%)
    1. Mitral valve more affected than Aortic valve
  3. Congenital Heart Disease (10-20%)
    1. Bicuspid aortic valve
    2. Pulmonary stenosis
    3. Ventricular Septal Defect
  4. Mitral Valve Prolapse (10-33%)
  5. Calcific Aortic Stenosis
  6. Asymmetric septal hypertrophy
  7. Marfan's Syndrome
  • Etiology
  • Infection sources
  1. IV Drug Abuse or IV Catheter related phlebitis
    1. Staphylococcus aureus
    2. Group A Streptococcus
    3. Gram Negative Rods
    4. Candida
  2. Dental procedures (including routine tooth cleaning)
    1. Viridans Streptococci
  3. Genitourinary procedures (includes Prostatic Massage)
    1. Enterococcus
    2. Gram Negative Rods
  4. Prosthetic Valve Recipient
    1. Staphylococcus epidermidis
    2. Staphylococcus aureus
    3. Diphtheroids
    4. Gram Negative Rods
    5. Candida
    6. Enterococcus
  5. Colonic neoplasm, villous adenoma or polyp
    1. Streptococcus bovis
  6. Homelessness or Alcoholism (and Body Lice)
    1. Bartonella Quintana
  7. Obstetric delivery
  8. Respiratory infection
  9. Skin Infection
  10. Cardiac surgery or cardiac catheterization
  1. Staphylococcus aureus (31%, esp. IV Drug Abuse)
  2. Viridans Streptococcus (17%)
  3. Coagulase negative staphylococci (11%)
  4. Enterococci (11%)
  5. Streptococcus bovis (7%)
  6. Other causes (<2-5% each)
    1. Miscellaneous Streptococcus
    2. Fungi
    3. Gram negative HACEK Bacilli (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, and Kingella)
    4. Gram Negative non-HACEK Bacilli
    5. Bartonella (responsible for high number of culture negative endocarditis cases)
    6. Brucella
    7. Coxiella
  • Pathophysiology
  1. Endocardial layer infection (typically Heart Valves)
    1. Mitral valve and aortic valve are most likely to be involved
    2. Starts with endothelial damage
      1. Turbulent flow (e.g. valvular stenosis or valvular regurgitation)
      2. Intravascular device-related injury (e.g. catheters)
      3. Chronic inflammation (e.g. IVDA)
    3. Injured endotholelium colonized with transient bacteremia (e.g. dental procedures, GI/GU surgery)
      1. Sewing cuff of prosthetic valves are most often affected
  2. Two factor combination predisposes to the development of endocarditis
    1. Bloodborne pathogen
      1. Bacteria
      2. Fungi
    2. Cardiac lesion: Intracardiac surface upon which the pathogens can adhere
      1. Prosthetic Heart Valve
      2. Native valve with congenital or acquired defect
  3. Timing of endocarditis: Prosthetic Heart Valves
    1. Early infection (<2 months after Heart Valve Replacement)
      1. Intraoperative prosthetic contamination
      2. Postoperative Infection
    2. Late infection (>12 months after Valve Replacement)
      1. Same bloodborne pathogen entry as with native valves
      2. Risk of perivalvular invasion (e.g. myocardial abscess, Pericarditis)
  • History
  1. Recent hospitalizations
  2. Recent infections
  3. Indwelling catheters or devices
  4. Dental procedures
  5. Known murmur
  6. Structural heart disease (e.g. valvular stenosis, valvular regurgitation)
  7. Prosthetic Heart Valve
  8. Prior Infective Endocarditis
  9. Intravenous Drug Abuse
  10. Hemodialysis
  11. Immunosuppression (e.g. Diabetes Mellitus, HIV Infection)
  • Symptoms
  • Typical Presentation
  1. Prodrome type symptoms
    1. Fever (80-90% of cases)
      1. May be absent in elderly or immunosuppressed
    2. Chills
    3. Sweats
    4. Myalgias (especially large muscle groups)
    5. Fatigue
    6. Weight loss
    7. Anorexia
    8. Arthralgia
    9. Malaise
    10. Pallor
  2. Non-productive cough
    1. Present in up to 24% of cases
    2. Better when supine, worse when upright
  3. Classic endocarditis symptoms as above
    1. May only be present in severe Acute Endocarditis
  • Signs
  • Classic Presentation (Osler)
  1. Congestive Heart Failure
    1. Present in severe cases
  2. Systolic Murmur from Heart Valve
    1. New murmur auscultated in 48% of careful examinations
    2. Most often a valve regurgitation murmur
    3. Characteristics change on serial exams
    4. Absent in tricuspid valve involvement (rare outside of IV Drug Abuse)
  3. Petechiae on mucus membranes (mouth, Conjunctiva)
  4. Splinter Hemorrhages
    1. Non-blanching linear lesions beneath nails
  5. Splenomegaly
  6. Osler Nodes
    1. Painful, raised, violaceous Nodules affecting pulp of fingers and toes
  7. Janeway Lesions
    1. Blanching, erythematous, painless hemorrhagic Nodules on palms or soles
  8. Roth Spots
    1. Small Retinal Hemorrhages with central pallor
    2. Exudative, edematous Retinal lesions
  9. Digital Clubbing
  10. Multiple foci of infection
    1. Example: Pneumonia, Perinephric Abscess
    2. Cerebral emboli
      1. Focal Cerebrovascular Accident findings
  • Precautions
  1. Endocarditis Diagnosis is often missed initially due to non-specific symptoms and signs
    1. Typically presents as a viral-like syndrome
    2. Patients often appear non-toxic initially
    3. Fever may not be present at visit (but reported at home)
    4. Murmurs are often absent or only intermittently present
    5. Consider Blood Cultures and close interval follow-up in undifferentiated fever with myalgias
  2. Red Flags for which Endocarditis should be considered
    1. Endocarditis risk factors
      1. Prosthetic or malformed Heart Valve
      2. Intravenous Drug Abuse (IVDA)
      3. Hemodialysis
    2. Unexplained symptoms
      1. Fever
      2. Night Sweats
      3. Systemic illness
  • Labs
  1. Blood Culture
    1. Obtain before starting empiric therapy
    2. Cultures should be obtained with careful antiseptic technique (not off IV lines)
    3. Obtain at least 3-5 ml for small children, 10 ml if older per culture (20 ml is preferred)
    4. Blood Culture timing need not coincide with fever (bacteremia is continuous)
    5. Obtain three cultures over at least one hour
      1. Three cultures are recommended as sufficient
      2. Test Sensitivity has been shown in the past to increase with additional cultures
        1. Four cultures: >90% sensitive
        2. Six cultures: 100% sensitive
    6. Repeat Blood Cultures (2 sets) are performed as part of the antibiotic protocol below
      1. Repeated if suspected endocarditis if initial 3 Blood Cultures negative at 24-48 hours
      2. If positive and on antibiotics, repeat every 24-48 hours until Blood Cultures are negative
    7. False Negative Rate: 10%
      1. Antibiotics prior to obtaining cultures or fastidious Bacteria
      2. Consider serologic testing for Bartonella, Coxiella, and Chlamydia
  2. Urinalysis
    1. Proteinuria
    2. Microscopic Hematuria
  3. Complete Blood Count
    1. Leukocytosis (only present in 50% of cases)
    2. Normochromic, Normocytic Anemia (50% of cases)
  4. Acute phase reactants and other lab markers
    1. May add little to diagnosis
      1. Low Test Specificity
      2. Low Test Sensitivity (increased in 66% of cases)
    2. C-Reactive Protein (C-RP) elevated
    3. Sedimentation Rate (ESR) elevated
    4. Complement
      1. CH50 or C3 decreased
    5. Rheumatoid Factor positive
      1. Circulating immune complex
    6. Procalcitonin
      1. Not recommended routinely in endocarditis evaluation
      2. Yu (2013) Am J Emerg Med 31(6):935-41 [PubMed]
  5. Markers of cardiac injury
    1. Serum Troponin
    2. Brain Natriuretic Peptide (BNP)
  6. Other labs
    1. Comprehensive metabolic panel
    2. Bartonella serology (Antibody titers >1:800) or tissue biopsy PCR
      1. Consider in culture negative cases, esp Alcoholism or Homelessness (or cat exposure)
  • Diagnostics
  1. Electrocardiogram (EKG)
    1. New AV nodal block (13% of cases)
      1. Periannular extension (valvular annulus, septum, Myocardium)
      2. Conduction abnormalities are seen in up to 26% of patients
      3. Associated with invasive infection and worse prognosis
      4. See complications below
      5. Meine(2001) Am Heart J 142(2):280-5 +PMID:11479467 [PubMed]
    2. Myocardial Ischemia or infarction
      1. Coronary emboli
  • Imaging
  • Diagnosis
  1. Transthoracic Echocardiogram
    1. Cornerstone of Duke Criteria for Infectious Endocarditis Diagnosis
    2. Recommended in all patients with suspected endocarditis
    3. Consider repeating Echocardiogram in 7-10 days in early cases, with high suspicion
    4. Findings
      1. Cannot differentiate active from healed lesion
      2. Vegetation in native valve endocarditis
        1. Test Sensitivity: 80% (range 50-90%), and very high in children
        2. Test Specificity: 90%
        3. Efficacy is much lower in Prosthetic Valve Endocarditis
  2. Transesophageal Echocardiogram
    1. Efficacy
      1. Test Sensitivity for native valve Infective Endocarditis: 90-100%
      2. Efficacy is slightly lower for prosthetic valves
    2. Indications
      1. Staphylococcus bacteremia
      2. Thoracic views non-diagnostic or limited by Obesity
      3. Prosthetic valve (shadowing interferes with adequate valve viewing)
      4. Endocarditis prior history
      5. Structural valve abnormality
  • Imaging
  • Additional
  • Differential Diagnosis
  1. Viral syndrome
  2. Acute Rheumatic Fever
  3. Atrial myxoma
  4. Systemic Lupus Erythematosus
  5. Primary neurologic disorder
  6. Occult neoplasm
  7. Myocarditis
  8. Bacteremia from other cause
  9. IV Drug Abuse
  10. Central catheter Sepsis
  11. Spinal Epidural Abscess
  • Management
  • Antibiotics
  1. Obtain Blood Cultures before starting empiric therapy (see above)
  2. In non-critically ill patients, delay treatment until Blood Culture and Echocardiogram confirm diagnosis
    1. If Sepsis or other hemodynamic instability, antibiotics may be started after cultures obtained
    2. Do not delay treatment beyond Blood Cultures in children (rapid decompensation may occur)
  3. Antibiotic Course
    1. Antibiotics IV for 4-6 week course
    2. Specific to organisms cultured
    3. Duration of therapy is based from the first day in which Blood Cultures are negative
      1. Obtain two sets of Blood Cultures every 24-48 until Blood Cultures are negative
    4. Antibiotics are initiated inpatient and then when clinically stable, at home via home care
      1. Re-evaluation in clinic following discharge should be within 7-14 days
      2. Obtain Complete Blood Count, Serum Creatinine and antibiotic levels at follow-up
  4. Antibiotics: Initial Empiric Treatment
    1. Protocol 1 - Native Valve
      1. Vancomycin 15-20 mg/kg every 8-12 hours IV (target trough 15-20 mcg/ml) AND
      2. Ceftriaxone 2 grams every 24 hours IV
    2. Protocol 2 - Native Valve
      1. Vancomycin 15-20 mg/kg every 8-12 hours IV (target trough 15-20 mcg/ml) AND
      2. Gentamicin 1 mg/kg every 8 hours IV or IM
    3. Protocol 3 - Prosthetic Valve
      1. Vancomycin 15-20 mg/kg every 8-12 hours IV (target trough 15-20 mcg/ml) AND
      2. Gentamicin 1 mg/kg every 8 hours IV or IM
      3. Rifampin 300 mg PO/IV every 12 hours
    4. Alternative agents
      1. Vancomycin alternative in native valve empiric therapy
        1. Daptomycin 6 mg/kg IV every 24 hours (every 48 hours if Creatinine Clearance <30 ml/min)
  5. Antibiotics: Viridans Streptococcus or Streptococcus bovis
    1. Penicillin Susceptible
      1. Penicillin G or Ceftriaxone for 4 weeks or
      2. Gentamicin AND (Penicillin G or Ceftriaxone) for 2 weeks or
      3. Vancomycin 15-20 mg/kg every 8-12 hours IV (target trough 15-20 mcg/ml) for 4 weeks
        1. Beta-lactams are preferred over Vancomycin, unless Antibiotic Resistance, allergy
    2. Penicillin Intermediate Sensitivity
      1. Gentamicin for 2 weeks AND (Penicillin G or Ceftriaxone) for 4 weeks or
      2. Vancomycin 15-20 mg/kg every 8-12 hours IV (target trough 15-20 mcg/ml) for 4 weeks
    3. Penicillin Resistant
      1. Gentamicin AND (Penicillin G or Ampicillin) for 4 to 6 weeks or
      2. Vancomycin 15-20 mg/kg every 8-12 hours IV (target trough 15-20 mcg/ml) for 6 weeks
  6. Antibiotics: Coagulase negative Staphylococcus
    1. Oxacillin-Susceptible (Coagulase negative Staphylococcus)
      1. Nafcillin or Oxacillin for 6 weeks AND
      2. Rifampin 300 mg IV/PO for 6 weeks AND
      3. Gentamicin 1 mg/kg every 8 hours IV or IM for 2 weeks
    2. Oxacillin-Resistant (Resistant coagulase negative Staphylococcus)
      1. Vancomycin 15-20 mg/kg every 8-12 hours IV (target trough 15-20 mcg/ml) for 6 weeks AND
      2. Rifampin 300 mg IV/PO for 6 weeks AND
      3. Gentamicin 1 mg/kg every 8 hours IV or IM for 2 weeks
  7. Antibiotics: Staphylococcus aureus
    1. MSSA
      1. Nafcillin or Oxacillin for 6 weeks AND
      2. Rifampin 300 mg IV/PO (if prosthetic valve) for 6 weeks AND
      3. Gentamicin 1 mg/kg every 8 hours IV or IM (if prosthetic valve) for 2 weeks
    2. MRSA
      1. Vancomycin 15-20 mg/kg every 8-12 hours IV (target trough 15-20 mcg/ml) for 6 weeks AND
      2. Rifampin 300 mg IV/PO (if prosthetic valve) for 6 weeks AND
      3. Gentamicin 1 mg/kg every 8 hours IV or IM (if prosthetic valve) for 2 weeks
  8. Antibiotics: Enterococcus
    1. Penicillin, Ceftriaxone, Gentamicin, Vancomycin sensitive
      1. Ceftriaxone and Ampicillin for 6 weeks or
      2. Gentamicin and (Ampicillin or Penicillin G) for 4 to 6 weeks (4 weeks for native valve) or
      3. Gentamicin and Vancomycin for 6 weeks
    2. Penicillin, and Vancomycin (and Streptomycin) sensitive, but resistant to Gentamicin
      1. Streptomycin and (Ampicillin or Penicillin G) for 4 to 6 weeks or
      2. Streptomycin and Vancomycin for 6 weeks
    3. Gentamicin and Vancomycin sensitive, but resistant to Penicillin
      1. Gentamicin and Ampicillin-Sulbactam (Unasyn) for 6 weeks or more or
      2. Gentamicin and Vancomycin for 6 weeks
  9. Antibiotics: Gram Negatives
    1. Ceftriaxone for 4-6 weeks (6 weeks for prosthetic valves)
  10. Antibiotics: Bartonella
    1. Ceftriaxone 2 g IV every 24 hours for 6 weeks (or until Bartonella confirmed as causative) AND
    2. Gentamicin 1 mg/kg IV every 8 hours for first 2 weeks (or Rifampin 300 mg IV or oral) AND
    3. Doxycycline 100 mg oral or IV twice daily for 6 weeks (or Azithromycin 250 mg daily)
  11. Experimental
    1. Oral antibiotics for endocarditis may be effective after using 2 weeks of IV antibiotic therapy as above
    2. May be indicated in left sided endocarditis native or prosthetic valve (mitral valve or aortic valve)
      1. Could be considered in non-compliant patients who refuse to continue IV medications
    3. Protocols
      1. Streptococcus or Enterococcus
        1. Amoxicillin 1000 mg four times daily (high dose)
      2. Staphylococcus (MSSA)
        1. Dicloxacillin 1000 mg four times daily (high dose)
      3. MRSA
        1. Linezolid
    4. References
      1. (2018) Presc Lett 25(11):62
      2. Iversen (2018) N Engl J Med +PMID:30152252 [PubMed]
  12. References
    1. Gilbert (2016) Sanford Guide to Antibiotics, IOS app accessed 4/13/2016
    2. Bonow (2006) J Am Coll Cardiol 48(3): e1-e148 [PubMed]
  • Management
  • Cardiovascular Surgery
  1. Indications (required in 50% of cases)
    1. Fungal endocarditis or other difficult to treat organisms
    2. Prosthetic Valve Endocarditis (higher risk of Heart Failure and invasive infection)
    3. Persistently positive Blood Culture despite therapy beyond the first week
    4. Recurrent emboli in the first 2 weeks of treatment
    5. Acute Heart Failure (pulmonary edema, Cardiogenic Shock)
    6. Severe valvular regurgitation (Aortic Regurgitation, Mitral Regurgitation)
      1. Best outcomes with early surgery (regardless of Infective Endocarditis)
    7. Large vegetation
    8. Paravalvular extension of infection
      1. Valve ring or myocardial abscess
      2. Valve dehiscence or fistula
      3. Heart Block
  2. Efficacy
    1. Based on retrospective study
    2. Early surgery improves survival over antibiotic alone
      1. Surgery within first 2 days of admission
      2. After 8 years of follow-up
        1. Surgery patient survival: 60%
        2. Medical therapy (antibiotics) survival: 35%
    3. Bishara (2001) Clin Infect Dis 33:1636-43 [PubMed]
  • Management
  • Other measures
  1. Remove IV catheters as soon as antibiotics are completed
  2. Obtain Echocardiogram at the end of antibiotic therapy
    1. Documents new baseline echo
  3. Remove implantable cardioverter Defibrillators and Pacemakers with evidence of device infection
  • Complications
  1. Cardiovascular complications (30-50% of cases)
    1. Heart Failure (right or left)
      1. Associated with poor prognosis
      2. Valve perforation
      3. Mitral chordae rupture
      4. Valve obstruction (large vegetation)
    2. Perivalvular abscess (up to 30-40% of cases)
      1. Associated with worse prognosis (systemic embolization risk)
      2. Consider when EKG abnormalities or persistent fever or bacteremia despite antibiotics
    3. Periannular extension into Myocardium
      1. May present as a new AV Nodal Block
      2. Increased mortality risk
      3. May require cardiac pacing
  2. Renal complications
    1. Glomerulonephritis
    2. Renal infarction
    3. Renal Abscess
  3. Musculoskeletal complications (esp. Staphylococcus aureus Infective Endocarditis)
    1. Vertebral Osteomyelitis
    2. Septic Arthritis
  4. Neurologic complications (33% of cases)
    1. Cerebrovascular Accident (CVA) or Transient Ischemic Attack (TIA)
      1. Typically affects the Middle Cerebral Artery distribution
    2. CNS emboli
      1. Stop Anticoagulation for 2 weeks in Staphylococcus aureus Prosthetic Valve Endocarditis with CNS emboli
    3. Mycotic aneurysm (rare)
    4. Meningitis
    5. Encephalitis
    6. Cerebral mycotic aneurysm
    7. Cerebral abscess
  5. Miscellaneous complications
    1. Splenic infarction
    2. Pulmonary Infarction
  • Prevention
  • Recurrent Endocarditis
  1. Obtain 3 Blood Culture sets at each subsequent febrile illness (prior to start of antibiotics)
  2. Practice good dental hygiene with regular dental visits
  3. SBE Prophylaxis for indicated procedures
  • Prognosis
  • Poor prognostic factors
  1. Advanced age
  2. Female gender
  3. Staphylococcus aureus Infective Endocarditis
  4. Healthcare-associated infection
  5. Heart Failure
  6. Prosthetic Valve Endocarditis
  7. Diabetes Mellitus
  8. Embolization complications
  9. Perivalvular Abscess
  10. Large vegetations
  11. Decreased mental status
  12. Other conditions associated with poor surgical candidacy
  • References
  1. (2015) Presc Lett 22(12): 69
  2. Orman and Mattu in Herbert (2015) EM:Rap 15(1): 9-11
  3. Pacheco and Rawani-Patel (2019) Crit Dec Emerg Med 33(5): 3-11
  4. Pelletier (1991) in Harrison's Medicine, p. 972
  5. Vlasic (2015) Crit Dec Emerg Med 29(7): 12-9
  6. Baddour (2015) Circulation 132: 1435-86 +PMID: 26373316 [PubMed]
  7. Habib (2009) Eur Heart J 30(19): 2369-413 [PubMed]
  8. Hoen (2013) N Engl J Med 368(15):1425-33 +PMID:23574121 [PubMed]
  9. Murdoch (2009) Arch Intern Med 169(5): 463-73 [PubMed]
  10. Pierce (2012) Am Fam Physician 85(10): 981-6 [PubMed]