Best Dx/Best Rx: Infective Endocarditis

Infective Endocarditis

Patrick T. O’Gara, MD

Harvard Medical School, Boston, MA

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 or fungi

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 39.4° to 40.6°C (102.9° to 105.1°F), 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 holosystolic murmur suggests rupture of chordae tendineae or fenestration of the leaflet
Heart failure
Cardiac rhythm disturbances
Occasionally, pericarditis

Cutaneous

Petechiae of the conjunctivae, oropharynx, skin, and legs
Linear subungual “splinter” hemorrhages of the base or middle of the nail bed
Osler nodes
Janeway lesions

Musculoskeletal

Myalgias
Arthralgias
Arthritis
Low back pain
Rheumatoid factor present 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

Central nervous system (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

Microbial (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 often develop
Strokes caused by cerebral emboli in ~ 15% of cases, resulting in the following:

Altered level of consciousness
Seizures
Fluctuating focal neurologic signs

Multiple aneurysms occur in some cases
Mycotic aneurysms cause the following:

Headache
Focal signs
Acute intracerebral or subarachnoid hemorrhage attributable to rupture
Mild meningeal irritation resulting from slow leakage

Septic emboli may cause multiple intracerebral foci of inflammation or small abscesses in acute endocarditis caused by Staphylococcus aureus
Toxic encephalopathy and 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 regurgitation may be difficult to detect on physical examination
Metastatic infections, including left-sided valve lesions
Neurologic manifestations
Peripheral emboli

Prosthetic Valve Endocarditis

Occurs in 1–2% of cases at 1 yr and in 4–5% of cases during the first 5 yr after valve implantation
Infection associated with invasion of perivalvular tissues
Valvular dysfunction, including sewing ring dehiscence
Myocardial abscesses
Fever
Petechiae, Roth spots, Osler nodes, Janeway lesions
Emboli

Differential Diagnosis

Tuberculosis, salmonellosis, intra-abdominal and genitourinary infections, and other disorders causing fever of undetermined origin
Juvenile rheumatoid arthritis, polymyalgia rheumatica
Acute rheumatic fever
Marantic (nonbacterial thrombotic) endocarditis
Polyarteritis nodosa
Systemic lupus erythematosus with antiphospholipid antibody syndrome
Cardiac myxoma
Neoplasms with paraneoplastic syndrome

Best Tests

Echocardiography

Transthoracic echocardiography

For detecting vegetations in native valve endocarditis: sensitivity, 60%; specificity, 90%
For detecting abscess: sensitivity, 18–28%

Transesophageal echocardiography

For detecting vegetations in native valve endocarditis: sensitivity, 95%; specificity, 100%
For detecting abscess: sensitivity, 76–87%
Better than transthoracic echocardiography 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 (change in preexisting murmur not sufficient)

Minor criteria

Predisposition: predisposing heart condition or injection drug use
Fever: temperature ≥ 38°C (100.4°F)
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 6 wk

Penicillin-Susceptible Viridans and Other Nonenterococcal Streptococci (minimum inhibitory concentration [MIC] < 0.2 µg/mL)

Penicillin G: preferred regimen

Dose: 12–18 million units IV 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 IM or IV daily in divided doses q. 8 hr for 2 wk (peak serum concentration should be ~ 3 µg/mL and trough concentrations < 1 µg/mL); ceftriaxone, 2 g IV daily as a single dose for 4 wk

Vancomycin: for patients with history of penicillin hypersensitivity

Dose: 30 mg/kg IV daily in divided doses q. 12 hr for 4 wk

Relatively Penicillin-Resistant Streptococci

MIC 0.2–0.5 µg/mL

Penicillin G + gentamicin: preferred regimen

Dose: penicillin G, 20–30 million units IV daily in divided doses q. 4 hr for 4 wk; gentamicin, 3 mg/kg IM or IV daily in divided doses q. 8 hr for 2 wk (peak serum concentration should be ~ 3 µg/mL and trough concentrations < 1 µg/mL)

MIC > 0.5 µg/mL

Penicillin G + gentamicin: preferred regimen

Dose: penicillin G, 20–30 million units IV daily in divided doses q. 4 hr for 4 wk; gentamicin, 3 mg/kg IM or IV daily in divided doses q. 8 hr for 2 wk (peak serum concentration should be ~ 3 µg/mL and trough concentrations < 1 µg/mL)

Vancomycin: regimen for patients with history of penicillin hypersensitivity

Dose: 30 mg/kg IV daily in divided doses q. 12 hr for 4 wk

Enterococci

Penicillin G + gentamicin: preferred regimen

Dose: penicillin G, 20–30 million units IV daily in divided doses q. 4 hr for 4–6 wk; gentamicin, 3 mg/kg IM or IV daily in divided doses q. 8 hr for 4–6 wk (peak serum concentration should be ~ 3 µg/mL and trough concentrations < 1 µg/mL)

Ampicillin + gentamicin

Dose: ampicillin, 12 g IV daily in divided doses q. 4 hr for 4–6 wk; gentamicin, dose as above

Vancomycin + gentamicin: regimen for patients with history of penicillin hypersensitivity

Dose: vancomycin, 30 mg/kg IV daily in divided doses q. 12 hr for 4–6 wk; gentamicin, 3–5 mg/kg IM or IV daily in divided doses q. 8 hr for 4–6 wk

Staphylococci (Methicillin Susceptible) in the Absence of Prosthetic Material

Nafcillin or oxacillin + gentamicin (optional): preferred regimen

Dose: nafcillin or oxacillin, 12 g IV daily in divided doses q. 4 hr for 4–6 wk; gentamicin, 3 mg/kg IM or IV daily in divided doses q. 8 hr for 3–5 days (peak serum concentration should be ~ 3 µg/mL and trough concentrations < 1 µg/mL)

Cephapirin + gentamicin (optional): alternative regimen for patients with history of penicillin hypersensitivity

Dose: cephapirin, 12 g IV daily in divided doses q. 4 hr for 4–6 wk; gentamicin, dose as above

Vancomycin: alternative regimen for patients with history of penicillin hypersensitivity

Dose: 30 mg/kg IV daily in divided doses q. 12 hr for 4–6 wk

Staphylococci (Methicillin Resistant) in the Absence of Prosthetic Material

Vancomycin

Dose as above

Staphylococci (Methicillin Susceptible) in the Presence of Prosthetic Material

Nafcillin or oxacillin + rifampin + gentamicin

Dose: nafcillin or oxacillin, 12 g IV daily in divided doses q. 4 hr for 6–8 wk; rifampin, 300 mg p.o., q. 8 hr for 6–8 wk; gentamicin (administer during the initial 2 wk), 3 mg/kg IM or IV 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 IV daily in divided doses q. 12 hr for 6–8 wk; rifampin, 300 mg p.o., q. 8 hr for 6–8 wk; gentamicin (administer during the initial 2 wk), 3 mg/kg IM or IV daily in divided doses q. 8 hr for 2 wk

HACEK Organisms

Ceftriaxone or another third-generation cephalosporin

Dose: 2 g IV daily as a single dose for 4 wk

Surgical Intervention

Indications for surgical débridement of vegetations and infected perivalvular tissue, with valve replacement or repair as needed

Heart failure attributable to valve dysfunction
Pseudoaneurysm, fistula,or valve perforation
Perivalvular invasion and abscess formation
Uncontrolled infection for > 1–3 wk despite optimal antimicrobial therapy
Recurrent emboli with persistent vegetation
Large mobile vegetation, especially involving the anterior mitral leaflet, with other indications for surgery such as severe mitral regurgitation
Mobile vegetation > 1.5 cm in maximal dimension
Fungal endocarditis
Prosthetic valve endocarditis with perivalvular invasion, especially with valve dehiscence
Endocarditis caused by Pseudomonas aeruginosa or other gram-negative bacilli that has not responded after 7–10 days of optimal 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
Anticoagulation should be reversed immediately in the event of CNS complications and interrupted for 1–2 wk after acute embolic stroke
There is no role for prophylactic aspirin

Best References

Durack DT. JAMA 2003;290:3250. [PMID 14693880]

Karchmer AW. Braunwald’s heart disease: a textbook of cardiovascular medicine. WB Saunders; 2007. p. 1713.

Murdoch DR, et al. Arch Intern Med 2009;169:463. [PMID 19273776]

* To obtain additional drug information, click on the DrugInfo tab in the left column, or click on the following link: http://search.medscape.com/drug-reference-search?queryText=

March 2011