Infective Endocarditis Case File

Infective Endocarditis Case File

Eugene C. Toy, Md, Michael d . Faulx, Md

Case 28

A 27-year-old intravenous drug user presents to the emergency department with 2 weeks of fever, productive cough, and pleuritic chest pain. He has had intermittent chills and drenching night sweats. He reports a decreased appetite and a 5-pound weight loss. He has had no sick contacts. The patient has also noted occasional blood in his urine. He denies any medical history and takes no prescription medications. He injects heroin daily, smokes tobacco and marijuana, but does not drink alcohol. He is unemployed and has had no recent travel. On examination, the patient is febrile to 101°F, is tachycardic to 115 bpm, and has a blood pressure of 92/ 65 mmHg. He is thin and ill-appearing. His mucous membranes are dry, and he has poor dentition. His sclera are anicteric. Neck exam reveals 6 cm of jugular venous distention above the sternal angle. The pulmonary exam reveals bronchial breath sounds over the right upper and left lower lobes. The cardiac exam reveals tachycardic, regular rate, a normal S1 and S2, and a III/VI blowing holosytolic murmur best heard at the left lower sternal border. His abdomen is soft and nontender with normal bowel sounds. Skin exam reveals scattered erythematous, nontender macules on his right palm and needle marks on both upper extremities. A complete blood count reveals an elevated white blood cell count to 19,000 cells/mm3 with 78% neutrophils and 11% bands. Chest x-ray reveals scattered multifocal wedge-shaped opacities in the right upper and left lower lobes. Electrocardiogram shows sinus tachycardia with a normal PR interval.

• What is the most likely diagnosis?
• What is the best next diagnostic step?
• What is the best next step in therapy?

Answer to Case 28

Infective Endocarditis

Summary: A 27-year-old IV drug user is presenting with fevers, chills, night sweats, cough, and chest pain for 2 weeks. He has a murmur on exam and evidence of septic pulmonary emboli on chest x-ray. He is ill-appearing, febrile, and tachycardic. His murmur is consistent with tricuspid regurgitation. He has abnormal breath sounds over multiple lung fields. His skin exam reveals Janeway lesions on his right palm. His white blood cell count is 19,000 cells/mm3 with 78% neutrophils and 11% bands. His ECG shows sinus tachycardia with no evidence of atrioventricular conduction delay.

• Most likely diagnosis: Infective endocarditis.
• Next diagnostic step: Blood cultures.
• Next step in therapy: Intravenous fluid resuscitation.

ANALYSIS

Objectives

1. Identify risk factors for developing infective endocarditis.
2. Recognize the common clinical manifestations of infective endocarditis, including Roth spots, Janeway lesions, Osler nodes, and splinter hemorrhages.
3. Become familiar with the workup for infective endocarditis, which includes blood cultures and echocardiography.
4. Know the indications for surgical management of infective endocarditis.

Considerations

A 27-year-old IV drug user is presenting with fevers, cough, and chest pain with a new murmur and septic emboli on chest x-ray suggestive of infective endocarditis. His initial management should include intravenous fluid resuscitation and broadspectrum antibiotics once blood cultures have been obtained. Infective endocarditis can lead to acute heart failure, which may be worsened with excessive volume administration, so you must carefully consider how much volume is given according to that patient’s volume status on exam. An echocardiogram should be performed to evaluate for vegetations on the heart valves, evidence of valvular regurgitation, or evidence of left ventricular dysfunction (decreased ejection fraction). An ECG should be performed to evaluate for atrioventricular conduction delay as the infection can involve the electrical system of the heart leading to varying degrees heart block. Other complications of endocarditis include septic emboli, most frequently to the brain, which can lead to stroke and/or brain abscess formation.

Laboratory evaluation will often reveal a leukocytosis, an elevated erythrocyte sedimentation rate, and C-reactive protein. Rheumatoid factor can also be positive.

Staphylococci and streptococci account for 80% of infective endocarditis cases. Initial empiric antibiotic therapy should include an antimicrobial with activity against methicillin-resistant Staphylococcus aureus, such as vancomycin, and the addition of either cefepime or a carbapenem if gram-negative bacteria are suspected or if the patient has prosthetic heart valves. The final antibiotic choice should be based on the sensitivities of the causative microorganism if identified through culture data. Patients are typically treated with intravenous antibiotics for 6 weeks. Surgical valve repair or replacement should be pursued if the patient has moderate to severe heart failure, severe aortic or mitral regurgitation, perivalvular abscess or fistula formation, fungal endocarditis, or very large vegetations.

Approach To:

Infective endocarditis

DEFINITIONS

Infective Endocarditis: Infection of the endocardium, typically the heart valves.

Roth spots: Exudative retinal hemorrhages, often with a pale or white center.

Osler nodes: Painful, palpable, red and purple lesions found on the pulps of the fingers and toes.

Janeway lesions: Flat, erythematous, nonpainful macules on the palms and soles.

Splinter hemorrhages: Small dark red or brown linear lesions found underneath the fingernail.

CLINICAL APPROACH

Etiology

Of all infective endocarditis cases, 80% are caused by staphylococci and streptococci species, including enterococcus. Other causative microorganisms include members of the hacek group of organisms (Haemophilus, Aggregatibacer, Cardiobacterium, Eikenella, and Kingella), bartonella, brucella, and Coxiella burnetii. Less common causes include other gram-negative bacteria and fungi, including candida and aspergillus. Risk factors include prosthetic heart valves, other intracardiac devices (such as pacemakers), rheumatic heart disease, unrepaired congenital heart disease, underlying structural valvular abnormalities, intravenous drug use, and hemodialysis.

Clinical Presentation

Most patients (80%) with infective endocarditis present with fever. Other presenting symptoms can include malaise, fatigue, weight loss, chills, and night sweats. Patients may present with symptoms of heart failure, including dyspnea on exertion, orthopnea, paroxysmal nocturnal dyspnea, and peripheral edema. Depending on the microbiologic cause, some patients may present with weeks to months of symptoms, while others will present much more rapidly, on the order of days.

In addition to the above mentioned symptoms, the history should focus on risk factors for developing endocarditis. Any cause of bacteremia, such as central venous lines or hemodialysis catheters, can lead to endocarditis, especially in patients with abnormal or prosthetic heart valves. Comorbid conditions can also increase the likelihood of infective endocarditis, including diabetes mellitus, HIV, and any cause of immunosuppression. Intravenous drug use is a major risk factor for developing endocarditis, particularly in younger patients. Iv drug users more commonly develop right-sided endocarditis (tricuspid or pulmonic valve) in comparison to non-IV drug users who typically get left-sided endocarditis (mitral or aortic valve).

The physical exam should first focus on the patient’s vital signs and the presence or absence of hypotension or shock. The patient’s volume status must be carefully assessed because the infection can lead to hypotension and intravascular volume depletion while simultaneously causing acute heart failure due to acute valvular regurgitation. The patient may display signs of heart failure, including jugular venous distention, peripheral edema, and pulmonary rales. A careful cardiovascular exam might reveal a regurgitant murmur. Tricuspid and mitral regurgitations are systolic murmurs, whereas aortic and pulmonic regurgitations are both diastolic murmurs. The exam should also include a search for peripheral stigmata of infective endocaritis that includes roth spots, osler nodes, janeway lesions, and splinter hemorrhages. Roth spots are exudative retinal hemorrhages often with a pale or white center. Osler nodes are painful, palpable, red and purple lesions found on the pulps of the fingers and toes. Janeway lesions are flat, erythematous, nonpainful lesions of the palms and soles. Splinter hemorrhages, which are not specific for endocarditis, are small dark red or brown linear lesions found underneath the fingernail in the nailbed.

Laboratory workup typically reveals a leukocytosis as well as an elevated erythrocyte

sedimentation rate and C-reactive protein. Rheumatoid factor is often positive.

Electrolyte abnormalities and renal failure may also be seen. Urinalysis may reveal

hematuria. Chest x-ray may reveal pulmonary cavitations or consolidations from

septic emboli.

Diagnosis

The clinical diagnosis of infective endocarditis is often based on the symptoms of the patient, laboratory findings, and imaging results. The first diagnostic step should be to obtain two sets of peripheral blood cultures as well as a blood culture from any indwelling catheter before the administration of antibiotics. Identification of the causative agent will greatly assist in the final choice of antibiotic. Blood cultures should be repeated every 24 hours until there is no evidence of bacteremia. An electrocardiogram should be obtained to evaluate for any conduction abnormalities such as atrioventricular block. Echocardiography should be pursued early. In general, a transthoracic echo is performed first to evaluate for any vegetations on the heart valves. However, if the transthoracic echo is negative and the suspicion for infective endocarditis remains high, or if the patient has prosthetic heart valves, then a transesophageal echo should be performed.

A clinical diagnosis of infective endocarditis can be made using the duke criteria, which include two major and five minor criteria. The first major criterion requires sustained positive blood cultures from a microorganism known to cause endocarditis or alternatively, a single positive blood culture or serology for Coxiella burnetii. The second major criterion requires evidence of endocardial involvement, which can be fulfilled by either new valvular regurgitation or echocardiographic evidence of valvular vegetations. The five minor criteria are (1) fever, (2) a predisposing condition (including IV drug use), (3) vascular phenomena, (4) immunologic phenomena, and (5) positive blood cultures that do not meet the first major criterion. Vascular phenomena include Janeway lesions, arterial emboli, septic pulmonary emboli, conjunctival hemorrhage, intracranial hemorrhage, and mycotic aneurysm. Immunologic phenomena include Roth spots, Osler nodes, a positive rheumatoid factor, and glomerulonephritis. A diagnosis of infective endocarditis can be made based on any of the following: two major criteria, one major criterion, and three minor criteria, or all five minor criteria (see Table 28-1).

Treatment

The initial treatment for infective endocarditis is generally fluid administration and antibiotics. However. the clinician must very cautiously provide volume as these patients can develop heart failure due to acute valvular regurgitation. A careful assessment of the patient’s volume status can guide fluid administration. Antibiotic choice is guided by the microbiologic cause (if known). Empiric regimens should include antibiotics with activity against methicillin-resistant Staphylococcus aureus (MRSA) such as vancomycin. If gram-negative bacteria are suspected or if the patient has a prosthetic heart valve, then an agent with gram-negative coverage such as cefepime or meropenem should be added to vancomycin. Fortunately, blood cultures are positive in almost 90% of patients with endocarditis, and final antibiotic choice can be tailored to the identified organism. Most patients are treated with antibiotics for a total of 6 weeks. 

Infectious-disease physicians, cardiothoracic surgeons, and cardiologists should all be involved in the management of these complex patients. Certain patients with infective endocarditis will require surgery. Indications for surgery include moderate

Figure 28-1. Intraoperative photograph of prosthetic aortic valve endocarditis. (Reproduced, with permission, from Jose Navia, M.D.)

to severe heart failure, severe aortic or mitral regurgitation, perivalvular abscess or fistula formation, prosthetic valve dehiscence or perforation, fungal endocarditis, and very large vegetations (>10 mm) to prevent embolization (Figures 28-1 and 28-2). Recent data have suggested that early surgery in patients with infective endocarditis and large vegetations has led to a decrease in mortality and embolic events.

Complications

In-hospital mortality for patients with infective endocarditis is about 15–20%, and 5-year mortality approaches 40%. The development of systolic heart failure is a very poor prognostic sign, with a mortality of >50% if there is no surgical intervention. Destruction of the valves can occur, which can lead to acute valvular insufficiency, 

Figure 28-2. Aortic valve vegetations ex vivo. (Reproduced, with permission, from Jose Navia, M.D.)

valvular dehiscence, and perforation. Abscesses and fistulas can form, which can lead to further valvular insufficiency or disruption of the conduction system. This can lead to varying degrees of heart block, including complete heart block. Systemic embolization is a major complication of infective endocarditis. The central nervous system is the most common and the most severe location for septic emboli. This can lead to ischemic or hemorrhagic strokes and the development of brain abscesses. The

spleen and kidney are other common sites for septic emboli. Systemic embolization most often occurs in left-sided endocarditis, although it can occur in right-sided endocarditis in the setting of a patent foramen ovale. Pulmonary septic emboli occur more frequently in right-sided endocarditis.

Prophylaxis

Antimicrobial prophylaxis is recommended for certain patients who are at high risk for developing endocarditis before certain procedures with high rates of postprocedural infectious complications. The current guidelines recommend that patients with prosthetic heart valves, a history of infective endocarditis, and congenital heart disease, and cardiac transplant patients with valvular regurgitation should be given antibiotic prophylaxis before undergoing invasive dental procedures. The guidelines recommend against antibiotic prophylaxis before nondental procedures, including upper endoscopy, colonoscopy, and transesophageal echo for all patients. The most common choice for prophylaxis is amoxicillin 2 g by mouth 30–60 minutes before the procedure. Cephalexin, azithromycin, and clindamycin are acceptable alternatives, but dosage should be based on the patient’s history of allergies.

CASE CORRELATION

• See also Case 6 (acute valvular regurgitation), Case 7 (chronic valvular regurgitation), and Case 10 (valvular stenosis).

COMPREHENSION QUESTIONS

28.1 A 55-year-old man with severe mitral regurgitation is undergoing a screening colonoscopy in 2 weeks. He also has a history of hypertension, gastroesophageal reflux, and osteoarthritis. His medications include lisinopril, chlorthalidone, omeprazole, and acetaminophen. He is allergic to penicillin. Prior to undergoing the colonoscopy, he should be prescribed which of the following:

A. Amoxicillin 2 grams per os (PO) 1 hour before the procedure

B. Metronidazole 1 gram PO 1 hour before the procedure

C. Clindamycin 600 mg PO 1 hour before the procedure

D. No antibiotics

28.2 A 76-year-old woman with severe aortic stenosis status following aortic valve replacement presents with left-sided facial droop, fever, and malaise. On exam, she is febrile to 100.5°F, is tachycardic to 105 bpm, and has a blood pressure of 105/60 mmHg. She is lethargic and has a III/VI early diastolic murmur in the aortic position. Her neurologic exam reveals left-sided facial droop. Laboratory workup shows a leukocytosis to 17,000 cells/mm³ and a creatinine of 2.0 mg/dL. In addition to IV fluids, antibiotics, and a head CT, the patient should undergo which diagnostic test:

A. Transthoracic echocardiogram

B. Bilateral carotid ultrasound

C. Transesophageal echocardiogram

D. CT angiogram of the head and neck

28.3 A 31-year-old IV drug user presents to the emergency department with fevers, chills, and night sweats. He is febrile, tachycardic, and hypotensive. His exam also reveals retinal hemorrhages with a pale white center, and he has several linear deposits in the nailbed of his right index and middle fingers. He is admitted to the hospital and given IV fluids and vancomycin. Serial sets of blood cultures are positive for Staphylococcus aureus. Transthoracic echocardiogram does not reveal any evidence of valvular vegetations. His ECG shows sinus tachycardia with a prolonged PR interval. What is the next step in management?

A. Transesophageal echocardiogram

B. Chest CT with contrast

C. Repeat transthoracic echo in 72 hours

D. Urine drug screen

ANSWERS

28.1 D . The patient does not require any antibiotic prophylaxis for infective endocarditis prior to his screening colonoscopy. The current guidelines recommend that patients with prosthetic heart valves, a history of infective endocarditis, congenital heart disease, and cardiac transplant patients with valvular regurgitation be given antibiotic prophylaxis before undergoing certain dental procedures. The guidelines recommend against antibiotic prophylaxis before nondental procedures, including upper endoscopy, colonoscopy, and transesophageal echo for all patients.

28.2 C . The patient should undergo a transesophageal echocardiogram to evaluate for infective endocarditis. Patients with prosthetic heart valves who are suspected to have infective endocarditis should undergo transesophageal echocardiogram instead of transthoracic echo. Although she is presenting with facial droop, a carotid ultrasound or a CT of the head and neck would not be the next diagnostic test of choice, given the high degree of suspicion for endocarditis.

28.3 A . The patient has a definite diagnosis of infective endocarditis, fulfilling one major criterion (sustained positive blood cultures of a microorganism known to cause endocarditis) and four minor criteria (fever, IV drug use, vascular phenomena, and immunologic phenomena) of the Duke criteria. His prolonged PR interval is concerning for perivalvular extension of the infection, such as an abscess, invading the conduction system of the heart. This is best evaluated with an urgent transesophageal echocardiogram.

CLINICAL PEARLS

• Ninety percent of patients with infective endocarditis have positive blood cultures, and staphylococci and streptococci represent 80% of identified causative microorganisms.
• The Duke criteria can be used to make a clinical diagnosis of infective endocarditis.
• Indications for surgery include moderate to severe heart failure, severe aortic or mitral regurgitation, perivalvular abscess or fistula formation, valvular dehiscence or perforation, fungal endocarditis, and very large vegetations (>10 mm) to prevent embolization.
• Complications of infective endocarditis include septic emboli, acute systolic heart failure, acute valvular regurgitation, perivalvular abscess and fistula, and atrioventricular conduction delays.
• The current guidelines recommend that patients with prosthetic heart valves, a history of infective endocarditis, congenital heart disease, and cardiac transplant patients with valvular regurgitation be given antibiotic prophylaxis before undergoing invasive dental procedures.

References

Baddour LM, Wilson WR, Bayer AS, et al. Infective endocarditis: Diagnosis, antimicrobial therapy, and management of complications: A statement for healthcare professionals from the committee on rheumatic fever, endocarditis, and Kawasaki disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: Endorsed by the Infectious Diseases Society of America. Circulation. 2005;111(23):e394–e434. 

Hoen B, Duval X. Clinical practice. infective endocarditis. N Engl J Med. 2013;368(15):1425–1433. 

Kang DH, Kim YJ, Kim SH, et al. Early surgery versus conventional treatment for infective endocarditis. N Engl J Med. 2012;366(26):2466–2473. 

Nishimura RA, Carabello BA, Faxon DP, et al. ACC/AHA 2008 guideline update on valvular heart disease: Focused update on infective endocarditis: A report of the American College of Cardiology/ American Heart Association task force on practice guidelines endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Catheter Cardiovasc Interv. 2008;72(3):E1–E12.

HomeCase FilesInfective Endocarditis Case File