Internal Medicine

Infective endocarditis (IE)


Multisystem disease that results from infection, usually bacterial, of the endocardial surface of the heart.


Sir William Osler, 1st Baronet, FRS FRCP (1849 – 1919) was a Canadian physician and one of the four founding professors of Johns Hopkins Hospital.

Infective endocarditis has been recognized as a pathological entity for hundreds of years and as an infectious process since the 19th century. In his landmark 1885 Gulstonian Lectures on malignant endocarditis, Sir William Osler presented a unifying theory in which susceptible patients developed ‘mycotic’ growths on their valves followed by “transference to distant parts of microbes”. The intervening 130 years have witnessed dramatic growth in our understanding of IE as well as fundamental changes in the disease itself. Medical progress, novel at-risk populations and the emergence of antimicrobial resistance have led to new clinical manifestations of IE.


Global epidemiology of causative pathogens involved in endocarditis: The causative agents of infective endocarditis differ geographically. | CoNS, Coagulase-negative staphylococci; HACEK, Haemophilus species, Aggregatibacter species, Cardiobacterium hominis, Eikenella corrodens, and Kingella species; Strep, streptococcal species; VGS, viridans group streptococci. | Murdoch DR, Corey GR, Hoen B, Miró JM, Fowler VG Jr, Bayer AS, Karchmer AW, Olaison L, Pappas PA, Moreillon P, Chambers ST, Chu VH, Falcó V, Holland DJ, Jones P, Klein JL, Raymond NJ, Read KM, Tripodi MF, Utili R, Wang A, Woods CW, Cabell CH, International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS) Investigators. Arch Intern Med. 2009 Mar 9; 169(5):463-73.


Risk factors:

  • Rheumatic heart disease (M/C predisposing cardiac condition for IE)
    • M/C involved site: Mitral valve
  • Prosthetic valves (20%) and cardiac devices (7%): Permanent pacemakers and cardioverter-defibrillators
  • Congenital heart disease (12%)
  • Structural heart disease:
    • Mitral valve prolapse (M/C predisposing structural abnormality, 7–30%)
  • Other factors:
    • Injection drug use (IDU)
    • Human immunodeficiency virus (HIV) infection
    • Health care-associated IE: Extensive healthcare system contact
Cahill, T. J., & Prendergast, B. D. (2016). Infective endocarditis. The Lancet, 387(10021), 882–893.


  • Staphylococcus aureus (M/C)
  • Coagulase-negative S. aureus (CoNS) (M/C early Prosthetic Valve IE)
  • Staphylococcal epidemidis (prosthetic valves or other nosocomial infection)
  • Enterococcus faecalis (#3 M/C) & Streptococcus bovis (commensals in colon)
    • Pre-existing colonic lesionsColorectal cancer & ulcerative colitis
  • HACEK organosism (Gram-negative & live on mouth/throat)
  • Q fever: Coxiella burnetii (rare)
    • Infected animal → Q fever → IE
      • Immunocompromised
      • Pregnant women
      • Valve defects
Pierce, D., Calkins, B. C., & Thornton, K. (2012). Infectious endocarditis: diagnosis and treatment. American family physician, 85(10), 981–986.

Streptococci and staphylococci collectively account for approximately 80% of IE cases:

Bacteria Streptococci viridians Staphylococcus aureus
Infection Subacute Acute
Virulence Low High
Site Mouth Skin
Valves Damaged only Damaged or healthy
Vegetations Small Large
Valve destruction No Yes



Nonbacterial Thrombotic Endocarditis (NBTE)/Marantic Endocarditis
Incidence (in order of pressure gradients): Aortic valve > Mitral valve > Tricuspid valve > Pulmonary valve

Infection → Transient bacteraemia → Microorganism-NBTE interaction

Infective endocarditis

Pathogenesis of endocarditis: a) Pathogens gain access to the bloodstream, for example via an intravenous catheter, injection drug use or from a dental source. b) Pathogens adhere to an area of abnormal cardiac valve surface. c) Some pathogens, such as S. aureus, obtain intracellular access to the valve endothelium. d) The infected vegetation is created by burying of the proliferating organism within a protective matrix of serum molecules. e) Vegetation particles can detach and disseminate to form emboli. These may lead to complications such as ischemic stroke, mycotic aneurysms and infarcts or abscesses at remote sites. | Werdan, K., Dietz, S., Löffler, B., Niemann, S., Bushnaq, H., Silber, R. E., … Müller-Werdan, U. (2014). Mechanisms of infective endocarditis: pathogen-host interaction and risk states. Nature reviews. Cardiology, 11(1), 35–50. doi:10.1038/nrcardio.2013.174
Mechanisms of infective endocarditis: a) Valve colonization as a consequence of mechanical injury. 1) Nonbacterial thrombotic endocarditis. 2) Bacteria bind to coagulum and colonize it during transient bacteraemia. Adhered monocytes release tissue factor and cytokines. 3) More platelets are attracted and become activated and the vegetation grows. 4) Endothelial cells are infected and can be lysed by bacterial products, or bacteria can persist inside the cells. b) Valve colonization as a consequence of an inflammatory endothelial lesion. 1) Activated endothelial cells express integrins that promote the local deposition of fibronectin; bacteria such as S. aureus adhere to this protein. 2) Bacteria are internalized and endothelial cells release tissue factor and cytokines, causing blood clotting and promoting the extension of inflammation and vegetation formation. 3) Infected endothelial cells can be lysed by bacterial products or bacteria can persist inside the cells. | Werdan K, et al. Mechanisms of infective endocarditis: pathogen-host interaction and risk states. Nat Rev Cardiol. 2014;11:35–50.

Types of valvular lesions:


  • Immune complex deposition in the kidney: 
    • Glomerulonephritis
  • Embolisation:
    • Organ infarction
  • Infected valve → Impaired function
    • Cardiac valve insufficiency
    • Regurgitation
  • Metastatic lesions
    • Acute arthritis
    • Splenic, mesenteric, brain, perivalvular abscess
    • Osteomyelitis
End-organ manifestations of endocarditis A) CT scans of pyogenic brain abscess and embolic stroke with haemorrhagic conversion. B) CT scan demonstrating multiple septic pulmonary emboli. C) CT scan demonstrating peripheral wedge-shaped splenic infarcts. D) Roth spots on funduscopic exam. E) Infarcts affecting multiple fingers. F) Explanted mitral valve with vegetation. G) Explanted aortic valve leaflet with vegetation and perforation. H) Pacemaker lead with vegetation. Roth spots photo courtesy of Walter B. Holland, MD. | Eisenbarth, G. S., & Gottlieb, P. A. (2004). Autoimmune Polyendocrine Syndromes. New England Journal of Medicine, 350(20), 2068–2079.

Clinical Features


  • Fever (7-10 days)
  • Chills, rigour, night sweats
  • General malaise, weakness
  • Loss of appetite, weight loss
  • Amenorrhoea (females)


  • Monoarticular arthralgia (Only in acute endocarditis as part of septicemia)
  • Diffuse myalgia
  • Petechiae (50%)

Immune complex formation:

  • Roth’s spots (white-centred retinal haemorrhages secondary to septic emboli within the retina)
  • Osler Nodes (3–5%): Tender raised red lesions on hands & feet


  • Splinter haemorrhages: Small red streaks under nails
  • Janeway lesions (3–5%): Small non-tender, red macules/nodules on palms/soles)

Case study:

A 34-year-old man presented to the eye emergency department with reduced vision in the right eye that had developed that morning. He was well, apart from episodes of dizziness and dyspnea after exercise during the previous 4 months. These episodes had started 1 week after the patient had undergone a dental treatment. Previous extensive investigations had been inconclusive. His retinal appearance and symptoms prompted referral to the cardiology team, which admitted him that day. He was afebrile but had a pansystolic murmur and a solitary splinter hemorrhage on the right thumb. Echocardiography revealed moderate-to-severe mitral-valve regurgitation, with thickening and signs of vegetations. The ejection fraction was 65%. The other values were normal. Four sets of blood cultures yielded Streptococcus viridans, and intravenous antibiotics were started immediately. His symptoms improved, and his visual acuity gradually improved from 20/200 at presentation to 20/20 8 months after presentation. His right fundal appearance is shown, at presentation (Panel A), 3 days later (Panel B), and 3 months later (Panel C). The presence of white-centered hemorrhages (Roth spots) should prompt the consideration of possible infective endocarditis. A comparison of Panel A and Panel B (3 days apart) shows how quickly such spots can change. Monitoring of the patient’s mitral-valve regurgitation, which was started after complete resolution of the endocarditis, is ongoing. | Mahroo, O. A., & Graham, E. M. (2014). Roth Spots in Infective Endocarditis. New England Journal of Medicine, 370(25), e38.


Modified Duke’s criteria:

  • Requirement (M=Major, m=minor):
    • Definite endocarditis = (2M) or (1M + 3m) or (5m)
    • Possible endocarditis = (1M + 1m) or (3m)
    • Rejected IE:
      • Firm alternative diagnosis for symptoms
      • Or sustained resolution of manifestation with antibiotic therapy for ≤ 4 days,
      • Or No pathological evidence of IE at surgery/autopsy, after antibiotic therapy for ≤ 4 days
  • Major criteria:
    • Positive blood culture
      • 2 separate positive blood cultures
      • Persistent positive blood cultures taken > 12 hours apart
      • ≥ 3 positive cultures taken over > 1 hour
    • Endocardial involvement
      • Positive echocardiogram
      • New valvular regurgitation
  • Minor criteria:
    • Predisposing valvular or cardiac abnormality
    • IV drug misuse
    • Pyrexia
    • ≥ 38°C
    • Embolic phenomenon
    • Vasculitic phenomenon
    • Blood cultures suggestive organism
    • Suggestive echocardiographic findings

Blood culture


  • Transthoracic echocardiogram (TTE)
  • Cardiac MRI
  • PET-CT
Imaging modalities for diagnosis of endocarditis: a) Transthoracic echocardiography demonstrating native mitral valve vegetation. b) Cardiac MRI, systolic frame demonstrating vegetations in the sub-tricuspid valve chordal apparatus with adherent thrombus (white asterisk) and posterior mitral valve leaflet (black asterisk). c) PET-CT – In this patient, infection of a prosthetic aortic valve was suspected but echocardiography was inconclusive. Using PET-CT, inflammatory leukocytes are visualized after taking up radiolabeled glucose, demonstrating an area of active infection on the aortic valve. | Ao, aorta; LV, left ventricle; Veg, vegetation. Pacemaker lead images courtesy of Gail Peterson, MD. | Holland, T. L., Baddour, L. M., Bayer, A. S., Hoen, B., Miro, J. M., & Fowler Jr, V. G. (2016). Infective endocarditis. Nature Reviews. Disease Primers, 2, 16059.


Antibiotic therapy:

  • Initial empiric therapy: Vancomycin or ampicillin/sulbactam + aminoglycoside + rifampin (prosthetic valves)
Pierce, D., Calkins, B. C., & Thornton, K. (2012). Infectious endocarditis: diagnosis and treatment. American family physician, 85(10), 981–986.

Antibiotic prophylaxis:

Pierce, D., Calkins, B. C., & Thornton, K. (2012). Infectious endocarditis: diagnosis and treatment. American family physician, 85(10), 981–986.

Surgical management:

  • Indications:
    • Fungal infection
    • Antibiotic-resistant bacteria 
    • Left-sided IE caused by gram-negative bacteria
    • Persistent infection with positive blood cultures after one week of antibiotic therapy
    • One or more embolic events during the first two weeks of antibiotic therapy


Holland, T. L., Baddour, L. M., Bayer, A. S., Hoen, B., Miro, J. M., & Fowler Jr, V. G. (2016). Infective endocarditis. Nature Reviews. Disease Primers, 2, 16059.

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