BASICS
DESCRIPTION
- An infection of the valvular (primarily) and mural (rarely) endocardium
- System(s) affected: cardiovascular, endocrine/metabolic, hematologic/lymphatic, immunologic, pulmonary, renal/urologic, skin/exocrine, neurologic
- Synonym(s): bacterial endocarditis; subacute bacterial endocarditis (SBE); acute bacterial endocarditis (ABE)
EPIDEMIOLOGY
Incidence
- Increase in incidence in United States from 11 per 100,000 to 15 per 100,00 between 2000 and 2011
- 1.5-3.0% incidence 1 year after prosthetic valve replacement; at 5 years, the incidence is 3-6%.
- Increasing incidence of cardiovascular device-related infections, due to higher frequency of implantable devices, especially in the elderly
ETIOLOGY AND PATHOPHYSIOLOGY
- ABE: Staphylococcus aureus; Streptococcus groups A, B, C, G; Streptococcuspneumoniae; Staphylococcus lugdunensis; Enterococcus spp. (gram-positive); Haemophilus influenzae or parainfluenzae; Neisseria gonorrhoeae (gram-negative)
- SBE: α-Hemolytic streptococci (viridans group strep), Streptococcus bovis, Enterococcus spp., Staphylococcus aureus, Staphylococcus epidermidis (gram-positive); HACEK organisms: Haemophilus aphrophilus or paraphrophilus, Actinobacillus (Aggregatibacter) actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella kingae
- Endocarditis in IV drug abusers (tricuspid valve): Staphylococcus aureus, Enterococcus spp. (gram-positive); Pseudomonas aeruginosa, Burkholderia cepacia, other bacilli (gram-negative); Candida spp.
- Early prosthetic-valve endocarditis (<60 days after valve implantation): Staphylococcus aureus, Staphylococcus epidermidis (gram-positive); gram-negative bacilli; fungi: Candida spp., Aspergillus spp.
- Late prosthetic valve endocarditis (>60 days after valve implantation): α-Hemolytic streptococci, Enterococcus spp., S. epidermidis (gram-positive); Candida spp., Aspergillus spp.
- Culture-negative endocarditis: 10% of cases; Bartonella quintana (homeless); Brucella spp., fungi, Coxiella burnetii (Q fever), Chlamydia trachomatis, Chlamydophila psittaci, HACEK organisms; Abiotrophia (formerly B6-deficient streptococci); use of antibiotics prior to blood cultures
- Device-related endocarditis: coagulase-negative staphylococci or S. aureus
RISK FACTORS
- Injection drug use, IV catheterization, certain malignancies (colon cancer), poor dentition, chronic hemodialysis
- High-risk conditions
- Prosthetic cardiac valve, implantable devices (pacemaker, automatic implantable cardioverter defibrillator [AICD]), total parenteral nutrition
- Previous infective endocarditis (IE)
- Congenital heart disease (CHD): unrepaired cyanotic CHD, including palliative shunts and conduits; repaired CHD with prosthetic device during the first 6 months; repaired CHD with residual defects at or near prosthetic site; cardiac transplant with valvulopathy (1)[B]
GENERAL PREVENTION
- Maintain good oral hygiene.
- Antibiotic prophylaxis is only recommended for high-risk cardiac conditions (1)[B]-prosthetic heart valve, history of endocarditis, transplant with abnormal valvular function, CHD (see "Risk Factors"�).
- Procedures requiring prophylaxis
- Oral/upper respiratory tract: any manipulation of gingival tissue or periapical region of teeth or perforation of the oral mucosa (1)[B], invasive respiratory procedures involving incision, or biopsy of the respiratory mucosa merit prophylaxis., amoxicillin 2 g PO (if penicillin allergic, clindamycin 600 mg PO) 30 to 60 minutes before procedure or ampicillin 2 g IV/IM are 1st-line prophylactic choices. For penicillin-allergic patients use clindamycin 600 mg IV, or cephalexin 2 g PO, or azithromycin/clarithromycin 500 mg PO, or cefazolin/ceftriaxone 1 g IV/IM 30 minutes before procedure. Pediatric doses are amoxicillin 50 mg/kg PO (max 2 g), cephalexin 50 mg/kg PO (max 2 g), clindamycin 20 mg/kg PO (max 600 mg), and ampicillin or ceftriaxone 50 mg/kg (maximum 1 g) IM/IV.
- GI/GU: Only consider coverage for enterococcus (with penicillin, ampicillin, piperacillin, or vancomycin) for patients with an established infection undergoing procedures (1)[B].
- Cardiac valvular surgery or placement of prosthetic intracardiac/intravascular materials: perioperative cefazolin 1 to 2 g IV 30 minutes preop, or vancomycin 15 mg/kg (maximum 1 g) (penicillin-allergic patients) 60 minutes preop (1)[B]
- Skin: incision and drainage of infected tissue; use agents active against skin pathogens (e.g., cefazolin 1 to 2 g IV q8h or vancomycin 15 mg/kg q12h; max 1 g) if penicillin-allergic or if methicillin-resistant Staphylococcus aureus (MRSA) suspected
DIAGNOSIS
- Modified Duke Criteria for Diagnosis of IE (2)[B] (definite: 2 major criteria, or 1 major and 3 minor criteria, or 5 minor criteria; possible: 1 major and 1 minor criteria, or 3 minor criteria)
- Major clinical criteria
- Positive blood culture: isolation of typical microorganism for IE from two separate blood cultures or persistently positive blood culture
- Single positive blood culture for C. burnetii or anti-phase-1 IgG antibody titer >1:800
- Positive echocardiogram: presence of vegetation, abscess, or new partial dehiscence of prosthetic valve; must be performed rapidly if IE is suspected
- New valvular regurgitation (change in preexisting murmur not sufficient)
- Minor criteria
- Predisposing heart condition or IV drug use
- Fever ≥38.0 �C (100.4 �F)
- Vascular phenomena: major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhage, Janeway lesions
- Immunologic phenomena: glomerulonephritis, Osler nodes, Roth spots, rheumatoid factor (RF)
- Microbiologic evidence: positive blood culture but not a major criterion (excluding single positive cultures for coagulase-negative staphylococci and organisms that do not cause endocarditis) or serologic evidence of infection likely to cause IE
HISTORY
- Fever (>38 �C), chills, cough, dyspnea, orthopnea; especially in subacute endocarditis: night sweats, weight loss, fatigue
- Predisposition to IE (see "Risk Factors"�)
- Symptoms of transient ischemic attack, cerebrovascular accident (CVA), or myocardial infarction (MI) on presentation
PHYSICAL EXAM
- Most patients with IE have new murmur or change in existing murmur. Signs of heart failure (rales, edema) if valve function is compromised.
- Peripheral stigmata of IE: splinter hemorrhages in fingernail beds, Osler nodes on fleshy portions of extremities, "Roth spot"� retinal hemorrhages, Janeway lesions (cutaneous evidence of septic emboli), palatal or conjunctival petechiae, splenomegaly, hematuria (due to emboli or glomerulonephritis)
- Neurologic findings consistent with CVA, such as visual loss, motors weakness, and aphasia
DIFFERENTIAL DIAGNOSIS
Fever of unknown origin, infected central venous catheter, marantic endocarditis, connective tissue diseases, intra-abdominal infections, rheumatic fever, salmonellosis, brucellosis, malignancy, tuberculosis, atrial myxoma, septic thrombophlebitis �
DIAGNOSTIC TESTS & INTERPRETATION
- When patient is not critically ill; three sets of blood cultures drawn >2 hours apart from different sites before administration of antibiotics.
- In acutely ill patients, draw three sets of blood cultures over a 1-hour period prior to empiric antibiotic therapy.
- Leukocytosis common in acute endocarditis
- Anemia, decreased C3, C4, CH50, and RF in subacute endocarditis
- ESR, C-reactive protein (CRP)
- Hematuria, microscopic or macroscopic
- Consider serologies for Chlamydia, Q fever, Legionella, and Bartonella in "culture-negative"� endocarditis.
- Transthoracic or transesophageal echocardiogram (TTE/TEE) should be performed as soon as IE is suspected.
- Baseline ECG may provide clues to extension of infection.
- CT scan may help locate embolic abscesses (e.g., splenic abscess).
- Vegetations are composed of platelets, fibrin, and colonies of microorganisms. Destruction of valvular endocardium, perforation of valve leaflets, rupture of chordae tendineae, abscesses of myocardium, rupture of sinus of Valsalva, and pericarditis may occur.
- Emboli, abscesses, and/or infarction may occur in any organ system.
- Immune-complex glomerulonephritis
TREATMENT
MEDICATION
First Line
- Initial empirical treatment should be started after three sets of blood cultures have been drawn while waiting for a causative organism to be identified.
- Native valves: Ampicillin-sulbactam 12 g/day IV divided into 4 doses with gentamicin 3 mg/kg/day IV/IM in 2 or 3 doses. If penicillin allergic, use vancomycin 30 mg/kg/day IV in 2 doses with gentamicin 3 mg/kg/day IV/IM in 2 or 3 doses and with ciprofloxacin 1,000 mg/day PO or 800 mg/day IV, both in 2 doses (3)[A].
- Prosthetic valves: Vancomycin 30 mg/kg/day IV in 2 doses with gentamicin 3 mg/kg/day IV/IM in 2 doses and rifampin 1,200 mg/day PO in 2 doses, if <12 months postsurgery. If >12 months, use native valve regimen (3)[A].
- Penicillin-susceptible viridans group streptococci or S. bovis
- Native valve: penicillin G 12 to 18 million U/day IV continuously or in 4 to 6 doses or ceftriaxone 2 g/day IV/IM in 1 dose, both for 4 weeks (2)[B]
- Prosthetic valve: penicillin G 24 million U/day IV continuously or 4 to 6 doses for 6 weeks or ceftriaxone 2 g/day IV/IM in 1 dose � gentamicin 3 mg/kg IV/IM q24h for 2 weeks (peak gentamicin level 3 μg/mL and trough <1 μg/mL) (2)[B]
- Penicillin-resistant viridans group streptococci or S. bovis
- Native valve: penicillin G 24 million U/day IV, either continuously or in 6 equally divided doses or ceftriaxone 2 g/day IV/IM in 1 dose for 4 weeks + gentamicin 3 mg/kg IV/IM q24h for 2 weeks (peak gentamicin level 3 μg/mL and trough <1 μg/mL) (2)[B]
- Prosthetic valve: Regimen is equivalent, but length of therapy is 6 weeks for all antibiotics.
- Staphylococcus
- Native valve: oxacillin or nafcillin 12 g IV every day for 4 to 6 weeks. The use of gentamicin is optional (e.g., patients with severe sepsis) and at most limited to 3 days. According to BSAC and IDSA guidelines, for MRSA bacteremia, the use of gentamicin is no longer recommended for staphylococcal native valve IE. For oxacillin-resistant strains, use vancomycin 15 mg/kg/day IV q12h for 6 weeks for goal trough of 15 to 20 μg/mL (2)[B].
- Prosthetic valve: oxacillin or nafcillin 12 g/day IV in 4 to 6 doses + rifampin 300 mg IV/PO q8h, for 6 weeks, + gentamicin 3 mg/kg/day IV for first 2 weeks (peak gentamicin level 3 μg/mL and trough <1 μg/mL). For oxacillin-resistant strains, use vancomycin 15 mg/kg IV q12h, + rifampin 300 mg IV/PO q8h, both for 6 weeks, + gentamicin 3 mg/kg/day IV/IM in 2 to 3 doses for the first 2 weeks (peak gentamicin level 3 μg/mL and trough <1 μg/mL) (2)[B].
- Penicillin-sensitive Enterococcus, native or prosthetic valve: ampicillin 12 g IV divided q4h or penicillin G 18 to 30 million U/day IV continuously or in 6 doses plus gentamicin 3 mg/kg IV q8h for 4 to 6 weeks (peak gentamicin level 3 μg/mL and trough <1 μg/mL) (2)[B]. Consider expert consultation for penicillin-resistant enterococci.
- HACEK organisms: ceftriaxone 2 g IM or IV q24h for 4 weeks (2)[B] or ampicillin-sulbactam 12 g IV divided q4h for 4 weeks or ciprofloxacin 1 g/day PO or 800 mg/day IV in 2 equally divided doses for 4 weeks
- Cardiac device-related endocarditis: Whole device removal is recommended for all patients with lead infection, followed by antibiotic therapy based on organism susceptibility (4)[B].
- Precautions: In patients with renal impairment, dosage adjustment should be made for penicillin G, gentamicin, cefazolin, ampicillin, ampicillin/sulbactam, ciprofloxacin, and vancomycin. Rapid infusion of vancomycin <1 hour may cause "red-man syndrome"� due to histamine release, not an allergic reaction. Treat with antihistamines and decrease infusion rate.
- Interactions: Vancomycin + gentamicin increases renal toxicity. Rifampin increases the requirement for Coumadin and oral hypoglycemic agents.
Second Line
For patients allergic to penicillin: �
- Penicillin-susceptible or resistant viridans group streptococci or S. bovis: vancomycin 30 mg/kg (not to exceed 2 g/day) IV for 4 weeks (6 weeks for prosthetic valve endocarditis) for goal trough of 15 to 20 μg/mL (2)[B]
- Enterococcus, native or prosthetic valve: Desensitization to penicillin should be considered. Vancomycin 15 mg/kg (usual dose, 1 g) IV q12h, + gentamicin or streptomycin (peak gentamicin level 3 μg/mL and trough <1 μg/mL) for 4 to 6 weeks (6 weeks for prosthetic valve endocarditis) (2)[B]
- Staphylococcus of native valve: cefazolin 2 g IV q8h (not to be used in patients with immediate-type hypersensitivity to penicillin) for 4 to 6 weeks or vancomycin 30 mg/kg (usual dose, 1 g) IV q12h for a goal trough of 15 to 20 μg/mL, for 6 weeks (2)[B]
SURGERY/OTHER PROCEDURES
Surgery is required in 50% of IE cases. Indications include the following (3)[A]: �
- Heart failure due to of aortic or mitral valve disease
- Prevention of embolism: aortic or mitral valve vegetations >10 mm with prior embolic episodes; isolated very large vegetation >15 mm; in patients with major ischemic stroke, surgery is delayed for at least 4 weeks, if possible (5)[C].
- Uncontrolled infection: persistent fever and positive cultures >7 to 10 days; infection caused by fungi or resistant organism; presence of abscess, fistula, false aneurysm, or enlarging vegetations
- Early prosthetic valve IE
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
- Check gentamicin peak (~3 μg/mL) and trough (<1 μg/mL) levels if used for >5 days and with renal dysfunction. Perform twice-weekly BUN and serum creatinine while on gentamicin. Consider audiometry baseline and follow-up during long-term aminoglycoside therapy.
- Check vancomycin trough (15 to 20 μg/mL) levels in all patients (typically prior to 4th dose) (3)[B].
- Baseline ECG; monitor ECG for conduction disturbances/MI in initial weeks of therapy.
- TTE at the conclusion of therapy
- Blood cultures q48h until negative
PROGNOSIS
Late complications contribute to the poor prognosis of IE. The main complications are heart failure, reinfection, and cerebral emboli. 10-year survival is 60-90% (6)[A]. �
COMPLICATIONS
- Cerebral complications are the most frequent and severe, occurring in 15-20% of patients (1)[A].
- Emboli: arterial (e.g., MI, mesenteric, splenic, cerebral infarction), infectious (e.g., abscesses of heart, lung, brain, meninges, bone, pericardium)
- Neurologic events are the most frequent complications in patients with IE requiring ICU admission. Ischemic stroke is the presenting symptom of IE in 20% of cases (6)[A].
- Inflammatory/immune disorders (e.g., arthritis, myositis, glomerulonephritis)
- Other complications: congestive heart failure (CHF), ruptured valve cusp, sinus of Valsalva aneurysm, arrhythmia, and mycotic aneurysms
REFERENCES
11 Wilson �W, Taubert �KA, Gewitz �M, et al. Prevention of infective endocarditis: guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation. 2007;116(15):1736-1754.22 Baddour �LM, Wilson �WR, Bayer �AS, et al. Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America. Circulation. 2005;111(23):e394-e434.33 Hoen �B, Duval �X. Clinical practice. Infective endocarditis. N Engl J Med. 2013;368(15):1425-1433.44 Baddour �LM, Epstein �AE, Erickson �CC, et al. Update on cardiovascular implantable electronic device infections and their management: a scientific statement from the American Heart Association. Circulation. 2010;121(3):458-477.55 Byrne �JG, Rezai �K, Sanchez �JA, et al. Surgical management of endocarditis: the society of thoracic surgeons clinical practice guideline. Ann Thorac Surg. 2011;91(6):2012-2019.66 Sonneville �R, Mirabel �M, Hajage �D, et al. Neurologic complications and outcomes of infective endocarditis in critically ill patients: the ENDOcardite en REAnimation prospective multicenter study. Crit Care Med. 2011;39(6):1474-1481.
CODES
ICD10
- I33.0 Acute and subacute infective endocarditis
- I39 Endocarditis and heart valve disord in dis classd elswhr
- A54.83 Gonococcal heart infection
- B37.6 Candidal endocarditis
ICD9
- 421.0 Acute and subacute bacterial endocarditis
- 421.1 Acute and subacute infective endocarditis in diseases classified elsewhere
- 098.84 Gonococcal endocarditis
- 112.81 Candidal endocarditis
SNOMED
- 233850007 infective endocarditis (disorder)
- 301183007 Bacterial endocarditis (disorder)
- 61048000 Gonococcal endocarditis (disorder)
- 63553008 Candidal endocarditis (disorder)
- 73028002 staphylococcal endocarditis (disorder)
- 459056003 Acute infective endocarditis (disorder)
CLINICAL PEARLS
- Antibiotic prophylaxis is recommended for patients with artificial heart valves, history of IE, CHDs, and cardiac transplants with valvulopathy.
- TEE/TTE and blood cultures are the mainstays for the diagnosis of IE.
- Most common organisms involved in IE are viridians Streptococcus spp. and Staphylococcus.