
Infective Endocarditis
David T. Durack, M.B., D.Phil.
Duke University School of Medicine
Adolf W. Karchmer, M.D.
Harvard Medical School
Definition/Key Clinical Features
Differential Diagnosis
Best Tests
Best Therapy
Best References
Definition/Key Clinical Features
- Localized microbial infection of cardiac valves or mural endocardium caused by bacteria, fungi, rickettsiae, or chlamydiae
Subacute Bacterial Endocarditis (SBE)
- Insidious onset
- Fever
- Sweats
- Weakness
- Myalgias
- Arthralgias
- Malaise
- Anorexia
- Fatigue
- Splenomegaly, clubbing, and Osler nodes in long-standing SBE
Acute Bacterial Endocarditis
- Abrupt onset
- Rigors
- Fevers as high as 102.9° to 105.1° F (39.4° to 40.6° C), often remittent
- Cardiac
- Murmur
- New aortic diastolic murmur suggests dilatation of the aortic annulus or eversion, rupture, or fenestration of an aortic leaflet
- Sudden onset of loud mitral pansystolic murmur suggests rupture of chorda tendineae or fenestration of a mitral valve leaflet
- Congestive heart failure
- Cardiac rhythm disturbances
- Occasionally, pericarditis
- Cutaneous
- Petechiae of the conjunctivae, oropharynx, skin, and legs
- Linear subungual splinter hemorrhages of the lower or middle nail bed
- Osler nodes
- Janeway lesions
- Musculoskeletal
- Myalgias
- Arthralgias
- Arthritis
- Low back pain
- Rheumatoid factor in up to 50% of patients with endocarditis for > 6 wk
- Clubbing of fingers in < 15% of patients
- Ocular
- Petechial hemorrhages, flame-shaped hemorrhages, Roth spots, and cotton-wool exudates in the retina
- Embolic
- Significant arterial emboli occur in 30%50% of patients, causing the following:
- Stroke
- Monocular blindness
- Acute abdominal pain, ileus, and melena
- Pain and gangrene in the extremities
- CNS emboli are common
- Coronary emboli, often asymptomatic, can cause myocardial infarction
- Pulmonary emboli common in right-sided endocarditis, causing pulmonary infarcts or focal pneumonitis
- Splenic
- Splenomegaly in 15%30% of patients
- Splenic infarcts in up to 40% of patients
- Splenic abscesses in ~ 5% of patients
- Renal
- Microscopic hematuria in ~ 50% of patients
- Embolic renal infarction
- Diffuse membranoproliferative glomerulonephritis
- Mycotic aneurysms
- Occur in any artery in 2%8% of patients, causing the following:
- Pain or headache
- Pulsatile mass
- Fever
- Sudden expanding hematoma
- Signs of major blood loss
- Neurologic
- Neurologic complications occur in 25%40% of cases
- Strokes caused by cerebral embolisms in ~ 15% of cases, causing the following:
- Altered level of consciousness
- Seizures
- Fluctuating focal neurologic signs
- Cerebral aneurysms occur in 1%5% of cases, causing the following:
- Headache
- Focal signs
- Acute intracerebral or subarachnoid hemorrhage caused by rupture
- Mild meningeal irritation resulting from slow leakage
- Brain abscesses may occur in acute endocarditis caused by Staphylococcus aureus
- Seizures
Endocarditis Associated with Parenteral Drug Use
- High fevers, chills, rigors, malaise, cough, and pleuritic chest pain
- Septic pulmonary emboli causing sputum production, hemoptysis, and signs suggesting pneumonia
- Cardiac murmurs
- Tricuspid insufficiency
- Metastatic infections
- Neurologic manifestations
- Peripheral emboli
Prosthetic Valve Endocarditis
- Occurs in 1%2% of cases at 1 yr and in 4%5% of cases at 4 yr after implantation
- Infection of perivalvular tissues
- Valvular dysfunction
- Myocardial abscesses
- Fever
- Petechiae, Roth spots, Osler nodes, Janeway lesions
- Emboli
Differential Diagnosis
- Tuberculosis, salmonellosis,
gastrointestinal and genitourinary infections, and other disorders
causing fever of undetermined origin
- Juvenile rheumatoid arthritis, polymyalgia rheumatica
- Acute rheumatic fever
- Marantic endocarditis
- Polyarteritis nodosa
- Systemic lupus erythematosus with antiphospholipid antibody syndrome
- Cardiac myxoma
- Neoplasms
Best Tests
- Echocardiography
- Transthoracic echocardiography
- For detecting vegetations in native valve endocarditis: sensitivity, 60%; specificity, 90%
- For detecting abscess: sensitivity, 18%28%; specificity, 99%
- Transesophageal echocardiography
- For detecting vegetations in native valve endocarditis: sensitivity, 95%; specificity, 100%
- For detecting abscess: sensitivity, 76%87%; specificity, 96%
- Better
than transthoracic for evaluating patients with suspected prosthetic
valve endocarditis and for detecting paravalvular abscesses
- Blood culture
- Incubate for 5 days (Bartonella species may need > 5 days for isolation)
- Blood cultures are negative in 5%20% of patients with endocarditis
- Serologic tests
- Can diagnose endocarditis caused by Bartonella, Legionella, and Brucella species; Chlamydia psittaci and Coxiella burnetii in cases of culture-negative endocarditis
- Duke criteria for the diagnosis of infective endocarditis
- Definite
- Pathologic criteria
- Microorganisms:
demonstrated by culture or histologically in a vegetation, in a
vegetation that has embolized, or in an intracardiac abscess specimen
- Pathologic lesions: vegetation or intracardiac abscess confirmed by histologic examination showing active endocarditis
- Clinical criteria (see definition of terms, below)
- Two major criteria
- One major and three minor criteria
- Five minor criteria
- Possible
- Findings consistent with infective endocarditis that fall short of definite but are not rejected
- Rejected
- Firm alternative diagnosis for manifestations of infective endocarditis
- Resolution of endocarditis syndrome with antibiotic therapy for ≤ 4 days
- No pathologic evidence of infective endocarditis at surgery or autopsy, with antibiotic therapy for ≤ 4 days
- Definitions of terms used in Duke criteria for diagnosis of infective endocarditis
- Major criteria
- Positive blood cultures for any one of the following:
- Typical microorganism consistent with diagnosis from two separate blood cultures
-
- Viridans streptococci, Streptococcus bovis, or HACEK organisms (Haemophilus, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella, Kingella)
-
- Community-acquired S. aureus or enterococci, in the absence of a primary focus
-
- Persistently positive blood cultures, defined as microorganisms consistent with diagnosis from any one of the following:
- At least two blood samples drawn > 12 hr apart
- Three of three or a majority of more than three blood cultures drawn, with first and last samples drawn at least 1 hr apart
- Evidence of endocardial involvement
- Echocardiogram positive for infective endocarditis (any one of the following)
- Oscillating
intracardiac mass on valve or supporting structures, in the path of
regurgitant jets, or on implanted material, in the absence of an
alternative anatomic explanation
- Abscess
- New partial dehiscence of prosthetic valve
- New valvular regurgitation (changing of preexisting murmur not sufficient)
- Minor criteria
- Predisposition: predisposing heart condition or I.V. drug use
- Fever: temperature ≥ 100.4° F (38° C)
- Vascular
phenomena: major arterial emboli, septic pulmonary infarcts, mycotic
aneurysm, intracranial hemorrhage, conjunctival hemorrhages, Janeway
lesions
- Immunologic phenomena: glomerulonephritis, Osler nodes, Roth spots, rheumatoid factor
- Microbiologic
evidence: positive blood culture but not meeting a major criterion (see
above; excludes single positive cultures for coagulase-negative
staphylococci, diphtheroids, and organisms that do not commonly cause
endocarditis) or serologic evidence of active infection with organism
consistent with infective endocarditis
- Echocardiogram consistent with infective endocarditis but not meeting a major criterion (see above)
Best Therapy
Drug Therapy
- Effective treatment requires identification of the etiologic agent and determination of its antimicrobial susceptibility
- Antibiotic
therapy for subacute or indolent disease can be delayed until results
of blood cultures are known; in fulminant infection or valvular
dysfunction requiring urgent surgical intervention, begin empirical
antibiotic therapy promptly after blood cultures have been obtained
- For prosthetic valve endocarditis, treat for 68 wk
Penicillin-Susceptible Viridans and Other Nonenterococcal Streptococci (minimum inhibitory concentration [MIC] < 0.2 ΅g/ml)
- Penicillin G: preferred regimen
- Dose: 1218 million units I.V. daily in divided doses q. 4 hr for 4 wk
- Penicillin G + gentamicin or ceftriaxone: preferred regimen
- Dose:
penicillin G, dose as above; gentamicin, 3 mg/kg I.M. or I.V. daily in
divided doses q. 8 hr for 2 wk (peak serum concentration should be ~ 3
΅g/ml and trough concentrations < 1 ΅g/ml); ceftriaxone, 2 g I.V.
daily as a single dose for 2 wk
- Vancomycin: for patients with history of penicillin hypersensitivity
- Dose: 30 mg/kg I.V. daily in divided doses q. 12 hr for 4 wk
Relatively Penicillin-Resistant Streptococci
- MIC 0.20.5 ΅g/ml
- Penicillin G + gentamicin: preferred regimen
- Dose:
penicillin G, 2030 million units I.V. daily in divided doses q. 4 hr
for 4 wk; gentamicin, 3 mg/kg I.M. or I.V. daily in divided doses q. 8
hr for 2 wk (peak serum concentration should be ~ 3 ΅g/ml and trough
concentrations < 1 ΅g/ml)
- MIC > 0.5 ΅g/ml
- Penicillin G + gentamicin: preferred regimen
- Dose:
penicillin G, 2030 million units I.V. daily in divided doses q. 4 hr
for 4 wk; gentamicin, 3 mg/kg I.M. or I.V. daily in divided doses q. 8
hr for 4 wk (peak serum concentration should be ~ 3 ΅g/ml and trough
concentrations < 1 ΅g/ml)
- Vancomycin: regimen for patients with history of penicillin hypersensitivity
- Dose: 30 mg/kg I.V. daily in divided doses q. 12 hr for 4 wk
Enterococci
- Penicillin G + gentamicin: preferred regimen
- Dose:
penicillin G, 2030 million units I.V. daily in divided doses q. 4 hr
for 46 wk; gentamicin, 3 mg/kg I.M. or I.V. daily in divided doses q.
8 hr for 46 wk (peak serum concentration should be ~ 3 ΅g/ml and
trough concentrations < 1 ΅g/ml)
- Ampicillin + gentamicin
- Dose: ampicillin, 12 g I.V. daily in divided doses q. 4 hr for 46 wk; gentamicin, dose as above
- Vancomycin + gentamicin: regimen for patients with history of penicillin hypersensitivity
- Dose: vancomycin, 30 mg/kg I.V. daily in divided doses q. 12 hr for 46 wk; gentamicin, dose as above
Staphylococci (Methicillin Susceptible) in the Absence of Prosthetic Material
- Nafcillin or oxacillin + gentamicin (optional): preferred regimen
- Dose:
nafcillin or oxacillin, 12 g I.V. daily in divided doses q. 4 hr for
46 wk; gentamicin, 3 mg/kg I.M. or I.V. daily in divided doses q. 8 hr
for 35 days (peak serum concentration should be ~ 3 ΅g/ml and trough
concentrations <1 ΅g/ml)
- Cefazolin + gentamicin (optional): alternative regimen for patients with history of penicillin hypersensitivity
- Dose: cefazolin, 12 g I.V. daily in divided doses q. 4 hr for 46 wk; gentamicin, dose as above
- Vancomycin: alternative regimen for patients with history of penicillin hypersensitivity
- Dose: 30 mg/kg I.V. daily in divided doses q. 12 hr for 46 wk
-
Staphylococci (Methicillin Resistant) in the Absence of Prosthetic Material
Staphylococci (Methicillin Susceptible) in the Presence of Prosthetic Material
- Nafcillin or oxacillin + rifampin + gentamicin
- Dose:
nafcillin or oxacillin, 12 g I.V. daily in divided doses q. 4 hr for
68 wk; rifampin, 300 mg p.o., q. 8 hr for 68 wk; gentamicin
(administer during the initial 2 wk), 3 mg/kg I.M. or I.V. daily in
divided doses q. 8 hr for 2 wk
Staphylococci (Methicillin Resistant) in the Presence of Prosthetic Material
- Vancomycin + rifampin + gentamicin
- Dose:
vancomycin, 30 mg/kg I.V. daily in divided doses q. 12 hr for 68 wk;
rifampin, 300 mg p.o., q. 8 hr for 68 wk; gentamicin (administer
during the initial 2 wk), 3 mg/kg I.M. or I.V. daily in divided doses
q. 8 hr for 2 wk
HACEK Organisms
- Ceftriaxone or another third-generation cephalosporin
- Dose: 2 g I.V. daily as a single dose for 4 wk
Surgical Intervention
- Indications for surgical debridement of vegetations and infected perivalvular tissue, with valve replacement or repair as needed
- Moderate to severe heart failure
- Vegetations that obstruct the valve orifice
- Perivalvular invasion and abscess formation
- Uncontrolled infection for > 13 wk despite maximal antimicrobial therapy
- Fungal endocarditis
- Prosthetic valve endocarditis with perivalvular invasion
- Endocarditis caused by Pseudomonas aeruginosa or other gram-negative bacilli that has not responded after 710 days of maximal antimicrobial therapy
Endocarditis Associated with Parenteral Drug Use
- In intravenous drug users with isolated right-sided S. aureus endocarditis, surgery should be postponed and antibiotic therapy continued for a prolonged period
Antithrombotic Therapy
- Anticoagulants can cause or worsen hemorrhage in patients with endocarditis but may be carefully administered when needed
- Prothrombin time should be carefully maintained at INR of 2.03.0
- Anticoagulation should be
reversed immediately in the event of CNS complications and interrupted
for 12 wk after acute embolic stroke
- Avoid heparin during active endocarditis if possible
Best References
Cabell, et al: Arch Intern Med 162:90, 2002
Durack: JAMA 290:3250, 2003
Lisby, et al: Infect Dis Clin North Am 16:393, 2002
Olaison, et al: Cardiol Clin 21:235, 2003
Towns, et al: Cardiol Clin 21:197, 2003
March 2005
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