Infective Endocarditis

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Diagnosis and reasoning

The history of prolonged fever associated with a pansystolic murmur in the apex, early clubbing and splenomegaly strongly raises the suspicion of infective endocarditis (IE). His blood cultures test positive for Streptococcus bovis (S. bovis), an organism well known to cause IE. In addition, his echocardiogram demonstrates an oscillatory mass attached to the mitral valve leaflet - most likely a cardiac vegetation. These findings are sufficient to confirm the clinical diagnosis. While many patients with IE have an obvious underlying etiology, at first glance, none is apparent in this patient. However, his full blood count (FBC) provides a hint by revealing the presence of microcytic hypochromic anemia. While IE itself may cause anemia (known as "anemia of chronic disease"), this is usually normocytic normochromic in nature. Microcytic hypochromic anemia is often due to chronic blood loss (iron deficiency anemia), or secondary to haemoglobinopathies such as thalassemia. In addition, there is a well recognized relationship between S. bovis infection and the presence of gastrointestinal neoplasia. As carcinoma of the colon may cause occult GI blood loss resulting in iron deficiency anaemia, this mandates colonoscopy in this patient. His colonoscopy reveals the presence of a fungating, ulcerating mass in the sigmoid colon - most likely a malignancy. He needs IV antibiotic therapy, and a GI surgical consultation to determine further management of his colonic lesion.


Discussion

IE is caused by infection of the endocardial surface or of prosthetic material in the heart. The incidence is approximately 1.7 to 6.2 cases per 100,000 patient years, with a 2:1 male to female ratio. IE is almost always fatal if untreated. Even with treatment, the one year mortality is between 20% to 25%, while the 10 year mortality is almost 50%. Risk factors for IE include native valve lesions, prosthetic valves, congenital heart disease, pacemaker implantation, IV drug abuse, recent invasive procedures and a history of previous IE. More than 80% of cases are caused by Staphylococcus aureus or by species of Streptococcus or Enterococcus. Almost 90% patients with IE present with a fever, which may be associated with chills or constitutional symptoms. Cardiac murmurs are found in up to 85% of patients. IE is also known to cause vasculitic phenomena like splinter haemorrhages, Roth spots (exudative, hemorrhagic lesions of the retina) and emboli to the brain, lung, or spleen (which may be the presenting feature in up to 30% of patients). Peripheral stigmata of IE include Janeway lesions (macular, erythematous, nonpainful lesions on the palms and soles) and Osler's nodes (painful nodules in the pulps of the fingers and toes). However, these are uncommon in developed countries as patients usually present early. The FBC may show anemia and a neutrophil leukocytosis, while the ESR and CRP may be elevated. Urinalysis may show the presence of red blood cells and casts (secondary to glomerulonephritis). However, these findings are non-specific. The initial investigation of choice is transthoracic echocardiography (TTE), with findings suggestive of IE including cardiac vegetations, new onset valvular regurgitation, myocardial abscesses, and in patients with prosthetic valves, new dehiscence. A normal TTE in a patient at low risk for IE makes this diagnosis unlikely. However, patients at high risk for IE should undergo further evaluation via transoesophageal echocardiography (TOE), which has a higher sensitivity and specificity. Blood cultures should be obtained in all patients with suspected IE. Current guidelines recommend that 3 sets of blood cultures should be drawn from separate sites 1 hour apart. It is vital to perform this prior to commencing antibiotic therapy, as a false negative result may be obtained otherwise. Note that the bacteraemia in IE is constant and persistent - thus cultures need not be taken during fever peaks. Blood cultures may be negative in up to 14% of patients (this is termed "culture negative endocarditis"). While this is often due to prior antibiotic therapy, it may also indicate infection by a fastidious organism like Legionella, Coxiella, the HACEK group of organisms or fungi like Candida, Histoplasma or Aspergillus. In such patients, serological testing may identify certain pathogens. If infected tissue is available (via cardiac surgery or retrieval of embolic material), histological analysis may be of use. In 1994, a group at Duke University proposed criteria for assessing patients with suspected IE (the "Duke criteria"). Further modifications yielded the "modified Duke criteria", which have gained widespread acceptance. The modified Duke criteria include both pathological and clinical criteria. The clinical criteria are further classified into "Major" and "Minor" criteria. A diagnosis of IE requires the presence of either a pathological criterion or a combination of major and/or minor clinical criteria. An ECG is useful in assessing the presence of complications like heart blocks or conduction delays. The management of IE involves early and appropriate antibiotic therapy, with the type of antibiotic and duration of therapy depending on the pathogen. Surgery may be considered in uncontrolled infection despite optimal antibiotic therapy; in fungal endocarditis; in the presence of complications like congestive heart failure or perivalvular invasive disease; or in prosthetic valve endocarditis. This often involves valve replacement with a metallic or biological prosthesis, although valve sparing techniques exist. The complications of IE include cardiac complications like valvular regurgitation, abscess formation and heart failure; neurologic complicationslike strokes and mycotic aneurysms; systemic embolism to the spleen, the kidney, the liver, and the iliac or mesenteric arteries; and splenic abscess formation. S. bovis is a non-enterococcal Streptococcus in Lancefield's group D, and is a normal inhabitant of the human GI tract. There is a well recognized association between S. bovis infection and the presence of gastrointestinal neoplasia, although the pathogenesis is unclear. Thus, it is suggested that endoscopic screening for colonic polyps and malignancies should be performed in patients with S. bovis infection, even if asymptomatic. Anti-tuberculous therapy and NSAIDs are not indicated in this patient.


Take home messages

  1. IE is an uncommon but potentially fatal cause for prolonged fever.
  2. IE is almost always fatal if untreated, and has a high mortality even with treatment.
  3. Almost 90% patients with IE present with a fever, while cardiac murmurs are found in up to 85% of patients.
  4. The initial investigation of choice is TTE. If negative, a TOE should be considered in patients at high risk for IE.
  5. Three sets of blood cultures should be drawn from separate sites one hour apart, prior to antibiotic therapy. This need not be during peaks of fever.
  6. Culture negative IE may be due to prior antibiotic therapy or infection with fastidious organisms.
  7. Endoscopic screening for colonic polyps and malignancies should be considered in patients with S. bovis infection.

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  1. Archives of Surgery : Association of Streptococcus bovis Bacteremia With Colonic Neoplasia and Extracolonic Malignancy (2004)
  2. BMJ : Easily Missed - Infective endocarditis (2010)
  3. BMJ : Infective endocarditis (2006)
  4. NEJM: Infective Endocarditis in Adults (2001)