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- Symptoms and Signs
- Antibiotic regimens
- Key Points
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Infective endocarditis is infection of the endocardium, usually with bacteria (commonly, streptococci or staphylococci) or fungi. It causes fever, heart murmurs, petechiae, anemia, embolic phenomena, and endocardial vegetations. Vegetations may result in valvular incompetence or obstruction, myocardial abscess, or mycotic aneurysm. Diagnosis requires demonstration of microorganisms in blood and usually echocardiography. Treatment consists of prolonged antimicrobial treatment and sometimes surgery.
Endocarditis can occur at any age. Men are affected about twice as often as women. IV drug abusers and immunocompromised patients are at highest risk.
The normal heart is relatively resistant to infection. Bacteria and fungi do not easily adhere to the endocardial surface, and constant blood flow helps prevent them from settling on endocardial structures. Thus, 2 factors are typically required for endocarditis:
Rarely, massive bacteremia or particularly virulent microorganisms cause endocarditis on normal valves.
Endocarditis usually involves the heart valves. Major predisposing factors are congenital heart defects, rheumatic valvular disease, bicuspid or calcific aortic valves, mitral valve prolapse, hypertrophic cardiomyopathy, and prior endocarditis. Prosthetic valves are a particular risk. Occasionally, mural thrombi, ventricular septal defects, and patent ductus arteriosus sites become infected. The actual nidus for infection is usually a sterile fibrin-platelet vegetation formed when damaged endothelial cells release tissue factor.
Infective endocarditis occurs most often on the left side (eg, mitral or aortic valve). About 10 to 20% of cases are right-sided (tricuspid or pulmonic valve). IV drug abusers have a much higher incidence of right-sided endocarditis (about 30 to 70%).
Microorganisms that infect the endocardium may originate from distant infected sites (eg, cutaneous abscess, inflamed or infected gums, UTI) or have obvious portals of entry such as a central venous catheter or a drug injection site. Almost any implanted foreign material (eg, ventricular or peritoneal shunt, prosthetic device) is at risk of bacterial colonization, thus becoming a source of bacteremia and hence endocarditis. Endocarditis also may result from asymptomatic bacteremia, such as typically occurs during invasive dental, medical, or surgical procedures. Even toothbrushing and chewing can cause bacteremia (usually due to viridans streptococci) in patients with gingivitis.
Causative microorganisms vary by site of infection, source of bacteremia, and host risk factors (eg, IV drug abuse), but overall, streptococci and Staphylococcus aureus cause 80 to 90% of cases. Enterococci, gram-negative bacilli, HACEK organisms ( Haemophilus sp, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae), and fungi cause most of the rest. Why streptococci and staphylococci frequently adhere to vegetations and why gram-negative aerobic bacilli seldom adhere are unclear. However, the ability of S. aureus to adhere to fibronectin may play a role, as may dextran production by viridans streptococci.
After colonizing vegetations, microorganisms are covered by a layer of fibrin and platelets, which prevents access by neutrophils, immunoglobulins, and complement and thus blocks host defenses.
Endocarditis has local and systemic consequences.
Local consequences include formation of myocardial abscesses with tissue destruction and sometimes conduction system abnormalities (usually with low septal abscesses). Severe valvular regurgitation may develop suddenly, causing heart failure and death (usually due to mitral or aortic valve lesions). Aortitis may result from contiguous spread of infection. Prosthetic valve infections are particularly likely to involve valve ring abscesses, obstructing vegetations, myocardial abscesses, and mycotic aneurysms manifested by valve obstruction, dehiscence, and conduction disturbances.
Systemic consequences are primarily due to embolization of infected material from the heart valve and, primarily in chronic infection, immune-mediated phenomena. Right-sided lesions typically produce septic pulmonary emboli, which may result in pulmonary infarction, pneumonia, or empyema. Left-sided lesions may embolize to any tissue, particularly the kidneys, spleen, and CNS. Mycotic aneurysms can form in any major artery. Cutaneous and retinal emboli are common. Diffuse glomerulonephritis may result from immune complex deposition.
Infective endocarditis may have an indolent, subacute course or a more acute, fulminant course with greater potential for rapid decompensation.
Subacute bacterial endocarditis (SBE), although aggressive, usually develops insidiously and progresses slowly (ie, over weeks to months). Often, no source of infection or portal of entry is evident. SBE is caused most commonly by streptococci (especially viridans, microaerophilic, anaerobic, and nonenterococcal group D streptococci and enterococci) and less commonly by S. aureus, Staphylococcus epidermidis, Gemella morbillorum, Abiotrophia defectiva (formerly, Streptococcus defectivus), Granulicatella sp, and fastidious Haemophilus sp. SBE often develops on abnormal valves after asymptomatic bacteremia due to periodontal, GI, or GU infections.
Acute bacterial endocarditis (ABE) usually develops abruptly and progresses rapidly (ie, over days). A source of infection or portal of entry is often evident. When bacteria are virulent or bacterial exposure is massive, ABE can affect normal valves. It is usually caused by S. aureus, group A hemolytic streptococci, pneumococci, or gonococci.
Prosthetic valvular endocarditis (PVE) develops in 2 to 3% of patients within 1 yr after valve replacement and in 0.5%/yr thereafter. It is more common after aortic than after mitral valve replacement and affects mechanical and bioprosthetic valves equally. Early-onset infections (< 2 mo after surgery) are caused mainly by contamination during surgery with antimicrobial-resistant bacteria (eg, S. epidermidis, diphtheroids, coliform bacilli, Candida sp, Aspergillus sp). Late-onset infections are caused mainly by contamination with low-virulence organisms during surgery or by transient asymptomatic bacteremias, most often with streptococci; S. epidermidis; diphtheroids; and the fastidious gram-negative bacilli, Haemophilus sp, Actinobacillus actinomycetemcomitans, and Cardiobacterium hominis.
Symptoms and signs vary based on the classification but are nonspecific.
Initially, symptoms are vague: low-grade fever (< 39° C), night sweats, fatigability, malaise, and weight loss. Chills and arthralgias may occur. Symptoms and signs of valvular insufficiency may be a first clue. Initially, ≤ 15% of patients have fever or a murmur, but eventually almost all develop both. Physical examination may be normal or include pallor, fever, change in a preexisting murmur or development of a new regurgitant murmur, and tachycardia.
Retinal emboli can cause round or oval hemorrhagic retinal lesions with small white centers (Roth spots). Cutaneous manifestations include petechiae (on the upper trunk, conjunctivae, mucous membranes, and distal extremities), painful erythematous subcutaneous nodules on the tips of digits (Osler nodes), nontender hemorrhagic macules on the palms or soles (Janeway lesions), and splinter hemorrhages under the nails. About 35% of patients have CNS effects, including transient ischemic attacks, stroke, toxic encephalopathy, and, if a mycotic CNS aneurysm ruptures, brain abscess and subarachnoid hemorrhage. Renal emboli may cause flank pain and, rarely, gross hematuria. Splenic emboli may cause left upper quadrant pain. Prolonged infection may cause splenomegaly or clubbing of fingers and toes.
Symptoms and signs are similar to those of SBE, but the course is more rapid. Fever is almost always present initially, and patients appear toxic; sometimes septic shock develops. Heart murmur is present initially in about 50 to 80% and eventually in > 90%. Rarely, purulent meningitis occurs.
Because symptoms and signs are nonspecific, vary greatly, and may develop insidiously, diagnosis requires a high index of suspicion. Endocarditis should be suspected in patients with fever and no obvious source of infection, particularly if a heart murmur is present. Suspicion of endocarditis should be very high if blood cultures are positive in patients who have a history of a heart valve disorder, who have had certain recent invasive procedures, or who abuse IV drugs. Patients with documented bacteremia should be examined thoroughly and repeatedly for new valvular murmurs and signs of emboli.
If endocarditis is suspected, 3 blood cultures (20 mL each) should be obtained within 24 h (if presentation suggests ABE, 2 cultures within the first 1 to 2 h). Each set of cultures should be obtained from a separate, fresh venipuncture site (ie, not from preexisting vascular catheters). Blood cultures do not need to be done during chills or fever because most patients have continuous bacteremia. When endocarditis is present and no prior antibiotic therapy was given, all 3 blood cultures usually are positive because the bacteremia is continuous; at least one culture is positive in 99%. Premature use of empiric antibiotic therapy should be avoided in patients with acquired or congenital valvular or shunt lesions to avoid culture-negative endocarditis. If prior antimicrobial therapy was given, blood cultures should still be obtained, but results may be negative.
Echocardiography, typically transthoracic (TTE) rather than transesophageal (TEE), should be done. Although TEE is somewhat more accurate (ie, capable of revealing vegetations too small to be seen on TTE), it is invasive and more costly. TEE should be done when endocarditis is suspected in patients with prosthetic valves, when TTE is nondiagnostic, and when diagnosis of infective endocarditis has been established clinically.
Other than positive blood cultures, there are no specific laboratory findings. Established infections often cause a normocytic-normochromic anemia, elevated WBC count, increased ESR, increased immunoglobulin levels, and the presence of circulating immune complexes and rheumatoid factor, but these findings are not diagnostically helpful. Urinalysis often shows microscopic hematuria and, occasionally, RBC casts, pyuria, or bacteriuria.
Identification of the organism and its antimicrobial susceptibility is vital to guide treatment. Blood cultures may require 3 to 4 wk incubation for certain organisms; however, some proprietary, automated culture monitoring systems can identify positive cultures within a week. Other organisms (eg, Aspergillus sp) may not produce positive cultures. Some organisms (eg, Coxiella burnetii, Bartonella sp, Chlamydia psittaci, Brucella sp) require serodiagnosis; others (eg, Legionella pneumophila) require special culture media or PCR (eg, Tropheryma whippelii). Negative blood culture results may indicate suppression due to prior antimicrobial therapy, infection with organisms that do not grow in standard culture media, or another diagnosis (eg, noninfective endocarditis, atrial myxoma with embolic phenomena, vasculitis).
Infective endocarditis is definitively diagnosed when microorganisms are seen histologically in (or cultured from) endocardial vegetations obtained during cardiac surgery, embolectomy, or autopsy. Because vegetations are not usually available for examination, clinical criteria for establishing a diagnosis (with a sensitivity and specificity > 90%) have been developed (see Table: Revised Duke Clinical Diagnostic Criteria for Infective Endocarditis).
Revised Duke Clinical Diagnostic Criteria for Infective Endocarditis
Untreated, infective endocarditis is always fatal. Even with treatment, death is more likely and the prognosis is generally poorer for older people and people who have infection with resistant organisms, an underlying disorder, or a long delay in treatment. The prognosis is also poorer for people with aortic or multiple valve involvement, large vegetations, polymicrobial bacteremia, prosthetic valve infections, mycotic aneurysms, valve ring abscess, and major embolic events. Septic shock is more likely in patients with diabetes, acute renal insufficiency, S. aureusinfection, supraventricular tachycardia, vegetation size > 15 mm, and signs of persistent infection. The mortality rate for viridans streptococcal endocarditis without major complications is < 10% but is virtually 100% for Aspergillus endocarditis after prosthetic valve surgery.
The prognosis is better with right-sided than left-sided endocarditis because tricuspid valve dysfunction is tolerated better, systemic emboli are absent, and right-sided S. aureusendocarditis responds better to antimicrobial therapy.
Treatment consists of a prolonged course of antimicrobial therapy. Surgery may be needed for mechanical complications or resistant organisms. Typically, antimicrobials are given IV. Because they must be given for 2 to 8 wk, home IV therapy is often used.
Any apparent source of bacteremia must be managed: necrotic tissue debrided, abscesses drained, and foreign material and infected devices removed. Existing IV catheters (particularly central venous ones) should be changed. If endocarditis persists in a patient with a newly inserted central venous catheter, that catheter should also be removed. Organisms within biofilms adherent to catheters and other devices may not respond to antimicrobial therapy, leading to treatment failure or relapse. If continuous infusions are used instead of intermittent boluses, infusions should not be interrupted for long periods.
Drugs and dosages depend on the microorganism and its antimicrobial susceptibility (for typical regimens, see Table: Antibiotic Regimens for Endocarditis). Initial therapy before organism identification (but after adequate blood cultures have been obtained) should be broad spectrum to cover all likely organisms:
In all regimens, penicillin-allergic patients require substitution of vancomycin 15 mg/kg IV q 12 h for the penicillin.
Antibiotic Regimens for Endocarditis
IV drug abusers frequently do not adhere to treatment, abuse IV access lines, and tend to leave the hospital too soon. For such patients, short-course IV or (less preferably) oral therapy may be used. For right-sided endocarditis caused by methicillin-sensitive S. aureus, nafcillin 2 g IV q 4 h plus gentamicin 1 mg/kg IV q 8 h for 2 wk is effective, as is a 4-wk oral regimen of ciprofloxacin 750 mg po bid plus rifampin 300 mg po bid. Left-sided endocarditis does not respond to 2-wk courses.
Surgery (debridement, valve repair or replacement) is frequently required for abscess, persistent infection despite antimicrobial therapy (ie, persistent positive blood cultures or recurrent emboli), or severe valvular regurgitation.
Timing of surgery requires experienced clinical judgment. If heart failure caused by a correctable lesion is worsening (particularly when the organism is S. aureus, a gram-negative bacillus, or a fungus), surgery may be required after only 24 to 72 h of antimicrobial therapy. In patients with prosthetic valves, surgery may be required when TEE shows valve dehiscence on a paravalvular abscess, when valve dysfunction precipitates heart failure, when recurrent emboli are detected, or when the infection is caused by an antimicrobial-resistant organism.
After starting therapy, patients with penicillin-susceptible streptococcal endocarditis usually feel better, and fever is reduced within 3 to 7 days. Fever may continue for reasons other than persistent infection (eg, drug allergy, phlebitis, infarction due to emboli). Patients with staphylococcal endocarditis tend to respond more slowly. Diminution of vegetation size can be followed by serial echocardiography.
Relapse usually occurs within 4 wk. Antibiotic retreatment may be effective, but surgery may also be required. In patients without prosthetic valves, recrudescence of endocarditis after 6 wk usually results from a new infection rather than a relapse. Even after successful antimicrobial therapy, sterile emboli and valve rupture may occur up to 1 yr later.
Preventive dental examination and therapy before surgery to repair heart valves or congenital heart lesions is recommended.
The American Heart Association (AHA) recommends antimicrobial prophylaxis for patients at high risk of an adverse outcome from infective endocarditis (see AHA Guidelines ). Such patients include those with
Prosthetic heart valves
Previous infective endocarditis
Certain congenital heart diseases (CHD): Unrepaired cyanotic CHD (including palliative shunts and conduits), completely repaired CHD during the first 6 mo after surgery if prosthetic material or device was used, repaired CHD that has residual defects at or adjacent to the site of repair
Heart transplant recipients with valvulopathy
Most procedures for which prophylaxis is required for high-risk patients are oral-dental procedures that manipulate the gingiva or the periapical region of teeth or perforate the oral mucosa. Other procedures include those respiratory tract procedures in which mucosa is incised, and GI, GU, or musculoskeletal procedures that involve an area with an established infection (see Table: Procedures Requiring Antimicrobial Endocarditis Prophylaxis in High-Risk Patients).
Procedures Requiring Antimicrobial Endocarditis Prophylaxis in High-Risk Patients
For most patients and procedures, a single dose shortly before the procedure is effective. For oral-dental and respiratory procedures, a drug effective against viridans group streptococci is used (see Table: Recommended Endocarditis Prophylaxis During Oral-Dental or Respiratory Tract Procedures*)
Recommended Endocarditis Prophylaxis During Oral-Dental or Respiratory Tract Procedures*
For GI, GU, and musculoskeletal procedures on areas involving infected tissue, antibiotics should be selected based on the known organism and its sensitivities. If infection is present but the infecting organism has not been identified, antibiotics for GI and GU prophylaxis should be effective against enterococci (eg, amoxicillin or ampicillin, or vancomycin for patients who are allergic to penicillin). Antibiotics for skin and musculoskeletal prophylaxis should be effective against staphylococci and beta-hemolytic streptococci (eg, a cephalosporin or vancomycin or clindamycin if infection with methicillin-resistant staphylococci is possible).
Because the normal heart is relatively resistant to infection, endocarditis occurs mainly when there is a predisposing abnormality of the endocardium.
Predisposing cardiac abnormalities include congenital heart defects, rheumatic valvular disease, bicuspid or calcific aortic valves, mitral valve prolapse, hypertrophic cardiomyopathy, prior endocarditis, and presence of a prosthetic valve.
Local cardiac consequences include myocardial abscess, conduction system abnormalities, and sudden, severe valvular regurgitation.
Systemic consequences include immune phenomena (eg, glomerulonephritis) and septic emboli, which may affect any organ put particularly the lungs (with right sided endocarditis), kidneys, spleen, CNS, skin, and retina (with left-sided endocarditis).
Diagnose using blood cultures and Duke criteria.
Treat with a prolonged course of antimicrobial therapy; surgery may be needed for mechanical complications or resistant organisms.
Give antimicrobial prophylaxis for patients at high risk of an adverse outcome from infective endocarditis, including those with prosthetic heart valves, previous infective endocarditis, certain congenital heart diseases, or who are heart transplant recipients with valvulopathy.
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