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Infective Endocarditis 

Infective Endocarditis
Infective Endocarditis

Emily Shuman

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date: 20 May 2022

  1. A. Introduction

    1. a. Once uniformly fatal, infective endocarditis (IE) continues to cause significant morbidity and mortality. Early diagnosis by an astute clinician and proper therapy can substantially improve outcomes.

    2. b. Before the availability of effective antibiotics, IE was classified as acute or subacute based on the organism and the clinical course. Today these distinctions are less meaningful.

    3. c. Certain subgroups of patients are at increased risk for IE development and should be evaluated carefully for evidence of disease. They include (1) persons with preexisting valvular abnormalities, including congenital bicuspid aortic valves, and those with a history of rheumatic fever; (2) patients with prosthetic valves; and (3) intravenous drug users.

  2. B. Causes of Infective Endocarditis

    1. a. Staphylococci. IE caused by Staphylococcus aureus and Staphylococcus epidermidis has increased in frequency and now is more common than viridans streptococcal endocarditis. S. aureus is the most frequent cause of IE in those with a history of intravenous drug use and is an important cause of healthcare–associated endocarditis. S. epidermidis is the most common bacteria isolated in cases of prosthetic valve endocarditis.

    2. b. Streptococci. Viridans streptococci (Streptococcus salivarius, Streptococcus sanguis, Streptococcus mitis/mitior, and Streptococcus milleri) are the second most common cause of IE. Other streptococcal species, including enterococci, S. bovis (nonenterococcal group D Streptococcus, renamed S. gallolyticus and S. infantarius), and occasionally S. pneumoniae are important causes of IE as well.

    3. c. Gram-negative bacteria can occasionally cause endocarditis, usually in association with genitourinary or gastrointestinal procedures, surgery, or intravascular catheters.

    4. d. Fungi. Fungal endocarditis has a poorer prognosis than bacterial IE and is associated with injection drug use, long-term antimicrobial therapy, and chronic hyperalimentation therapy. Candida species account for the majority of cases of fungal IE.

    5. e. Culture-negative endocarditis is most frequently encountered in patients who have received prior antibiotics leading to sterile blood cultures. Certain organisms may be difficult to detect in routine culture systems, however. These include:

      1. i. HACEK group organisms. Haemophilus,Actinobacillus,Cardiobacterium,Eikenella, and Kingella are gram-negative organisms that often grow slowly in traditional blood culture systems. However, with automated blood culture systems, the HACEK organisms are easily isolated within the standard 5-day incubation period.

      2. ii. Nutritionally-variant streptococcal species (now known as Abiotrophia and Granulicatella species) require specific media supplementation for growth.

      3. iii. Fungi. Large vegetations are often found in patients with endocarditis associated with fungal infection. An intravascular source is frequently noted (e.g., an indwelling intravenous catheter). Candida species are easily isolated in routine cultures; however, Aspergillus is almost never recovered from cultures. Other rare fungal causes of IE, including Histoplasma capsulatum, may require special fungal cultures (lysis-centrifugation system).

      4. iv. Legionella, Brucella species, Coxiella burnetii (Q fever), Bartonella henselae (cat scratch disease), and Tropheryma whipplei (Whipple’s disease) are rare causes of culture-negative endocarditis.

  3. C. Clinical Manifestations of Infective Endocarditis. The clinical manifestations of endocarditis are variable but most closely depend on which organism is involved and whether the patient has left-sided (aortic or mitral) or right-sided (usually tricuspid) disease.

    1. a. Fever occurs in almost all patients; however, older adult patients, patients with congestive heart failure (CHF) or renal failure, and patients taking steroids or nonsteroidal antiinflammatory drugs (NSAIDs) may be afebrile. Other systemic symptoms, such as anorexia and malaise, are common.

    2. b. Murmurs. Although a cardiac murmur is a classic sign of endocarditis, a murmur may be absent in as many as 15% of patients, and a new or changing murmur is present in only 3%–5% and 5%–10% of patients, respectively.

    3. c. Low back pain, arthralgias, and myalgias are very common and may be the patient’s presenting symptoms.

    4. d. Splenomegaly may be seen in one-fourth to one-half of patients.

    5. e. Classic findings, including Osler’s nodes, Janeway lesions, Roth’s spots (retinal hemorrhages), petechiae of the palate or conjunctivae, and subungual splinter hemorrhages, are often not found, probably because of early treatment of disease in the antimicrobial era.

      Hot Key

      Although Osler’s nodes are typically violaceous nodules located on the pads of the fingers or toes, and Janeway lesions are typically erythematous and found on the palms or soles, the predominant distinction between the two is that Osler’s nodes are painful, whereas Janeway lesions are painless.

  4. D. Complications of Infective Endocarditis

    1. a. CHF. Pulmonary edema and hypotension may occur with significant left-sided (aortic and mitral) valve dysfunction, whereas peripheral edema may result from right-sided (tricuspid) disease.

    2. b. Myocardial abscess formation can lead to bundle branch block (aortic valve abscesses) or heart block (mitral valve abscesses). Perivalvular abscesses are common in patients with prosthetic valve endocarditis.

    3. c. Emboli. Left-sided endocarditis may result in visceral infarcts, including splenic, hepatic, renal, central nervous system, and mesenteric infarcts as well as cutaneous infarcts. Right-sided endocarditis may cause septic pulmonary emboli with pulmonary infarction, abscess formation, or both.

    4. d. Hematogenous seeding of other sites may occur, including bone (vertebral osteomyelitis), joint (septic arthritis), and other vessels (mycotic aneurysms).

  5. E. Approach to the Patient

    1. a. Patient history.

      1. i. IE is a diagnosis that is often missed; therefore, always make sure to include endocarditis in the head-to-toe approach to fever (see Chapter 48).

      2. ii. Be sure to ask the patient about risk factors for endocarditis (i.e., injection drug use, history of valvular disease or repair, recent procedures or surgery).

    2. b. Physical examination. In addition to performing a complete physical examination, pay special attention to the following:

      1. i. Funduscopic examination (to search for Roth’s spots)

      2. ii. Cardiovascular examination (to detect murmurs or evidence of CHF)

      3. iii. Skin and mucous membrane examination (to search for Osler’s nodes, Janeway lesions, splinter hemorrhages, and conjunctival or palatal petechiae)

      4. iv. Bone and joint examination (to detect septic joints or osteomyelitis)

    3. c. Laboratory studies. Patients who have an unexplained fever, have a low clinical probability of endocarditis, and are conscientious concerning follow-up can sometimes be evaluated as outpatients. Patients with fever and a prosthetic valve, history of injection drug use, or examination findings concerning for endocarditis and no obvious alternative source of infection are almost always admitted to rule out endocarditis.

      1. i. Blood cultures are the gold standard for diagnosis. A minimum of two sets of aerobic and anaerobic cultures are usually obtained; however, three sets may increase the sensitivity to greater than 90%.

        1. 1. Different venous sites are usually used to avoid confounding skin contamination.

        2. 2. Cultures should always be taken before initiating empiric antibacterial therapy.

      2. ii. Urinalysis. Abnormal urinalysis findings are common in endocarditis. Hematuria or proteinuria is common; red blood cell casts suggestive of glomerulonephritis should be sought.

      3. iii. Echocardiography. Because the duration of therapy may differ depending on which side of the heart (left or right) is involved, echocardiography is necessary to define which valve is infected and to identify complications such as myocardial abscesses. Transthoracic echocardiography is often performed first, followed by transesophageal echocardiography in cases in which the diagnosis is still in question; however, the cost-effectiveness of this stepped approach is unclear.

        1. 1. Transthoracic echocardiography (TTE), with a sensitivity of up to 75%, is not sensitive enough to rule out endocarditis. In addition, TTE is notoriously poor for ruling out mitral valve disease and evaluating prosthetic valves.

        2. 2. Transesophageal echocardiography (TEE) increases the sensitivity to >90% and is significantly better for evaluating the mitral valve.

  6. F. Treatment

    1. a. Empiric therapy. Empiric therapy should be initiated only when the patient appears unstable or acutely ill. Patients with stable symptoms for days to weeks should be watched carefully while not taking antibiotics until a causative agent is discovered. Ill patients should receive vancomycin and gentamicin pending cultures. Penicillin plus gentamicin is an appropriate empiric regimen in patients suspected of having viridans streptococcal endocarditis, but often these patients are not acutely ill and the diagnosis can be made with blood culture data before urgently starting therapy.

      Hot Key

      The benefits of adding gentamicin to vancomycin in IE include (1) synergy against S. aureus, which may decrease the duration of bacteremia; and (2) broader coverage against gram-negative and multiorganism infections, an important advantage in injection drug users and patients with prosthetic valves.

      1. i. Suspected prosthetic valve endocarditis may be treated with vancomycin, rifampin, and an aminoglycoside. This regimen will cover methicillin-resistant coagulase-negative staphylococci (common offenders) while treating possible enterococcal infection as well.

    2. b. Organism-specific therapy. The duration of therapy may vary depending on the causative organism, the severity of the illness, and whether disease is right or left sided.

      1. i. Viridans streptococcal infections are usually treated with penicillin or ceftriaxone with or without an aminoglycoside. Therapy most commonly lasts for 2–4 weeks.

      2. ii. Enterococcal infections usually require prolonged combination therapy and are often treated with ampicillin or vancomycin and an aminoglycoside for 4–6 weeks.

      3. iii. Staphylococcal infections

        1. 1. Methicillin-sensitive S. aureus (MSSA) infections may be treated with nafcillin or oxacillin.

        2. 2. Methicillin-resistant S. aureus (MRSA) infections may be treated with vancomycin.

        3. 3. Prosthetic valve staphylococcal infections should be treated with combination therapy with rifampin and 2 weeks of an aminoglycoside in addition to the previous agents when possible.

    3. c. Surgery. Valve replacement is often indicated when:

      1. i. Fungal infection is strongly suspected.

      2. ii. A prosthetic valve is infected.

      3. iii. Complications have developed (e.g., myocardial abscess, acute valvular dysfunction with refractory CHF).

      4. iv. Uncontrolled infection (inability to clear blood cultures).

      5. v. The patient has experienced more than one embolic event.

  7. G. Follow-Up

    1. a. Frequent examinations are essential. Listen carefully for a new or changing murmur, look closely for embolic phenomena, and watch for widening of the pulse pressure (which should alert you to possible aortic regurgitation).

      1. i. Bilateral disease. Although intravenous drug users more commonly have right-sided disease, they may also have left-sided or bilateral endocarditis. You should therefore continue to assess for possible left-sided involvement.

      2. ii. Persistent fever. Defervescence occurs within 1 week in 72% of patients. Prolonged fever is an important prognostic sign. Drug reactions are the most common cause of persistent or recurrent fever, but myocardial and metastatic abscess formation should always be considered.

    2. b. Electrocardiograms (EKGs). Lengthening of the PR interval or a new bundle branch block should prompt an echocardiogram to evaluate possible myocardial abscess formation (TEE is more sensitive). An EKG should be obtained on admission and on a frequent basis thereafter.

Suggested Further Readings

Baddour LM, Wilson WR, Bayer AS, et al. Infective endocarditis. Circulation 2005;111:3167.Find this resource:

Durack DT, Lukes AS, Bright DK. New criteria for diagnosis of infective endocarditis: utilization of specific echocardiographic findings. Duke Endocarditis Service. Am J Med 1994;96:200–9. (Classic Article.)Find this resource:

Hermans PE. The clinical manifestations of infective endocarditis. Mayo Clinic proceedings 1982;57:15–21. (Classic Article.)Find this resource:

Hoen B, Duval X. Infective endocarditis. N Engl J Med 2013;368:1425–33.Find this resource:

Lamas CC, Fournier P-E, Zappa M, et al. Diagnosis of blood culture-negative endocarditis and clinical comparison between blood culture-negative and blood culture-positive cases. Infection 2016;44:459–66.Find this resource: