Endocarditis is an infection of the valves of the heart.
Infection of the heart valves is thought to result from the colonization of damaged valvular endothelium by circulating pathogens. Endothelial damage may result from turbulent blood flow around the valve (congenital or rheumatic heart disease), direct injury from foreign bodies (e.g., intravenous catheters), or repeated intravenous injections of particles in intravenous drug users. Deposition of platelets and fibrin forms a thrombus at the site of the damaged endothelium. This is called nonbacterial thrombotic endocarditis (NBTE).
Organisms enter the bloodstream most often through the mouth (i.e., dental disease or dental procedures) or skin (i.e., trauma, injection drug use). Adhesion of bacteria to the damaged endothelium is enhanced by their ability to produce a glycocalyx.
Once the infection has begun, a combination of organisms and thrombus organize to form a vegetation (Figure 71–1). Destruction of the valve occurs at different rates depending on the virulence of the organism. As the valve is destroyed, symptoms of valvular regurgitation can develop. Organisms can spread to surrounding myocardium, resulting in abscess formation and destruction of the electrical conduction system.
Endocarditis. Note vegetations on mitral valve. Black arrows point to vegetations. (Reproduced with permission from Longo DL, Fauci AS, Kasper DL, et al. Harrison’s Principles of Internal Medicine. 18th ed. New York, NY: McGraw-Hill Education; 2012.)
As the vegetation on the valve enlarges, fragments can spread via the bloodstream (emboli), resulting in catastrophic effects, such as cerebrovascular accidents (CVAs) and metastatic infections to other organs. Prolonged infection as seen in subacute endocarditis can result in antigen–antibody complex formation. Deposition of these complexes can result in other clinical manifestations as described in the next section. Artificial materials within the heart, such as prosthetic heart valves, pacemakers, and defibrillators, serve as potential sites for infection.
In summary, the steps in the pathogenesis of endocarditis are as follows:
Formation of NBTE
Adherence of bacteria
Proliferation of bacteria within the vegetation
The clinical manifestations of infective endocarditis can include any of the following listed below. Depending on the virulence of the infecting pathogen, the time course of illness may be days (acute endocarditis; caused by, e.g., Staphylococcus aureus) or weeks to months (subacute endocarditis; caused by, e.g., viridans group streptococci).
Constitutional symptoms: fever (>80% cases), chills, night sweats, anorexia
Consequences of destruction of heart valves and associated structures: new murmur, heart failure, atrioventricular (AV) block (PR prolongation seen on ECG; Figure 71–2)
Left-sided endocarditis: CVAs or brain abscess (Figure 71–3) (new focal neurologic deficits), splenic or renal infarcts (abdominal or flank pain), and emboli to other sites manifesting as splinter hemorrhages (Figure 71–4), Janeway lesions (Figure 71–5), retinal hemorrhages (Figure 71–6), and conjunctival hemorrhages (Figure 71–7).
Right-sided endocarditis: septic pulmonary emboli (cough, shortness of breath, chest pain, hemoptysis).
Antigen–antibody deposition from uncontrolled infection: Osler’s nodes (Figure 71–8), Roth’s spots (Figure 71–9), glomerulonephritis (hematuria), and/or arthritis.
Atrioventricular block with sinus bradycardia. (Reproduced with permission from McKean SC, Ross JJ, Dressler DD, et al. Principles and Practice of Hospital Medicine. New York, NY: McGraw-Hill Education; 2012.)
Brain abscess. Red arrow points to a characteristic ring-enhancing lesion. The blue arrows point to two additional abscesses. (Reproduced with permission from Ropper AH, Samuels MA. Adams and Victor’s Principles of Neurology. 9th ed. New York, NY: McGraw-Hill Education; 2009.)
Splinter hemorrhage. Red arrow points to a splinter hemorrhage under the finger nail. (Reproduced with permission from Usatine RP, Smith MA, Mayeaux EJ Jr, et al. The Color Atlas of Family Medicine. New York, NY: McGraw-Hill Education; 2009.)
Janeway lesions. Red arrow points to a Janeway lesion. (Reproduced with permission from Wolff K, Johnson R, Saavedra A. Fitzpatrick’s Color Atlas & Synopsis of Clinical Dermatology. 7th ed. New York, NY: McGraw-Hill Education; 2013.)
Retinal hemorrhages. Blue arrow points to a retinal hemorrhage. (Reproduced with permission from Usatine RP, Smith MA, Mayeaux EJ Jr, et al. The Color Atlas of Family Medicine. New York, NY: McGraw-Hill Education; 2009. Photo contributor: Paul D. Comeau, MD.)
Conjunctival hemorrhages. Blue arrow points to one of several conjunctival hemorrhages. (Reproduced with permission from Fuster V, Walsh RA, Harrington RA. Hurst’s The Heart. 13th ed. New York, NY: McGraw-Hill Education; 2011.)
Osler’s node in pulp of big toe. Red arrow points to an Osler’s node. Note also Janeway lesions on sole of foot. Blue arrow points to a Janeway lesion. (Reproduced with permission from Usatine RP, Smith MA, Mayeaux EJ Jr, et al. The Color Atlas of Family Medicine. New York, NY: McGraw-Hill Education; 2009. Photo contributor: David A. Kasper DO, MBA.)
Roth’s spots. Note the central white spots characteristic of Roth’s spots (red arrow). (Reproduced with permission from Usatine RP, Smith MA, Mayeaux EJ Jr, et al. The Color Atlas of Family Medicine. New York, NY: McGraw-Hill Education; 2009. Photo contributor: Paul D. Comeau, MD.)
Bacteria are the most common causes of endocarditis, but occasionally fungi such as Candida are involved as well. The modern classification of pathogens causing endocarditis is divided into native valve versus prosthetic valve, with subclassifications within each group (Table 71–1). S. aureus is most common cause of native-valve infective endocarditis followed by viridans group Streptococci and Enterococcus species.
TABLE 71–1Etiology of Endocarditis by Category ||Download (.pdf) TABLE 71–1 Etiology of Endocarditis by Category
|Category ||Pathogen |
|Native valve |
| Community onset ||Viridans group streptococci, Staphylococcus aureus, Streptococcus bovis, Enterococcus species |
| Health care associated ||S. aureus, Enterococcus species, Staphylococcus epidermidis |
| Intravenous drug user ||S. aureus, gram-negative rods such as Pseudomonas, Candida species |
|Prosthetic valve |
| Early ||S. epidermidis, S. aureus |
| Late ||S. aureus, viridans group streptococci, Enterococcus species, S. epidermidis |
| Pacemaker or defibrillator ||S. epidermidis, S. aureus |
| Culture negative ||Prior antibiotics, Bartonella species, Coxiella burnetii, Brucella species, Tropheryma whipplei |
In patients who have prosthetic valves, pacemakers, or defibrillators in place, coagulase-negative staphylococci such as Staphylococcus epidermidis and S. aureus are the most common pathogens. Other less common pathogens that grow relatively well in routine culture media include the β-hemolytic streptococci, Streptococcus pneumoniae, HACEK organisms (Haemophilus aphrophilus, Aggregatibacter species, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae), and Candida species.
Pathogens that do not grow in routine blood culture media and require specialized testing for diagnosis include Bartonella species, Coxiella burnetii, Brucella species, and Tropheryma whipplei. These are cited as pathogens that cause “culture-negative” endocarditis. The most frequent cause of “culture-negative endocarditis” is the use of antimicrobials prior to obtaining blood cultures.
A definitive diagnosis of endocarditis requires direct pathologic examination and microbiologic analysis of the heart valve. Because in most cases the heart valve tissue is not available for evaluation, most clinicians use a combination of blood cultures and echocardiographic findings to make the diagnosis of infective endocarditis. The Modified Duke Criteria are the most frequently used criteria for making the diagnosis of endocarditis (Table 71–2) and help guide clinicians to make an accurate diagnosis.
TABLE 71–2Modified Duke Criteria for the Diagnosis of Infective Endocarditis ||Download (.pdf) TABLE 71–2 Modified Duke Criteria for the Diagnosis of Infective Endocarditis
|Definite infective endocarditis |
Microorganism demonstrated by culture or histology in a vegetation or in a vegetation that has embolized or in an intracardiac abscess
Pathologic lesions, vegetation or intracardiac abscess, confirmed by histology showing active endocarditis
|Major criteria |
Positive blood cultures of typical organism for infective endocarditis from two separate blood cultures or persistently positive blood culture or single culture positive for culture or serology consistent with Coxiella burnetii infection
Positive echocardiogram for infective endocarditis
New valvular regurgitation
|Minor criteria |
Predisposing heart condition or intravenous drug use
Vascular phenomena (arterial emboli, septic pulmonary infarcts, mycotic aneurysm, etc.)
Immunologic phenomena (Osler’s nodes, Roth’s spots, glomerulonephritis, etc.)
Microbiologic evidence not meeting major criteria
Infecting pathogens are most commonly recovered through blood cultures. To maximize sensitivity of the test, it is recommended to obtain three sets of blood cultures over at least an hour. Whenever possible, blood cultures should be obtained prior to administering antibiotics. In some rare cases of endocarditis due to organisms that do not grow easily in blood culture media (Bartonella species), serology can be used to help make the diagnosis.
Evaluation of valves for infection is best accomplished through echocardiography. TTE has reduced sensitivity when compared with a TEE to assess for vegetations and myocardial abscesses but is a less invasive test. Not only can echocardiogram identify new vegetations on valves, which are evidence of infection, but it can also assess the degree of valvular damage and complications such as perivalvular abscesses (Figure 71–10). ECG can be used to detect damage to the conducting system. The most common finding is PR prolongation in patients with aortic valve endocarditis and associated perivalvular abscess (see Figure 71–2).
Transesophageal echocardiography in endocarditis. Segmented abscess cavity (labeled A) between the left atrium (labeled LA) and the aortic root (labeled AO). Red arrow indicates the wall that segments the abscess. RA = right atrium; RVOT = right ventricular outflow tract. (Reproduced with permission from Fuster V, Walsh RA, Harrington RA. Hurst’s The Heart. 13th ed. New York, NY: McGraw-Hill Education; 2011.)
Without treatment, endocarditis is always fatal, so prompt effective therapy is essential. The treatment for endocarditis always includes antimicrobial therapy, and in some cases, surgical removal of the infected valve is indicated as well. Empiric therapy for endocarditis is recommended in cases where the patient has hemodynamic instability, severe disease, evidence of embolic disease, or large vegetations.
Empiric antimicrobial coverage should be active against methicillin-resistant S. aureus, viridans group streptococci, enterococci, and HACEK organisms. A common empiric regimen is vancomycin plus ceftriaxone. Specific antimicrobial therapy should be instituted when the results of blood cultures and antibiotic susceptibility tests are known. Antimicrobial therapy for endocarditis is usually required for 4 to 6 weeks.
Surgical therapy is either indicated or should be strongly considered in patients with severe congestive heart failure, perivalvular abscesses, infections refractory to medical management, and embolic events with large vegetations.
In patients with prior endocarditis, a prosthetic heart valve, or select types of congenital heart disease, antibiotic prophylaxis is recommend prior to certain procedures. Guidelines support giving antibiotics, such as amoxicillin, to these high-risk patients at the time of invasive dental procedures (not for routine cleanings), surgery involving respiratory mucosa, or surgery involving infected tissues.