Endocarditis, Infective

Descriptive text is not available for this image BASICS

Infective endocarditis (IE) is an infection of the inner layer of the heart including the valves (native/prosthetic), interventricular septum, intracardiac devices, chordae tendineae, and mural endocardium. IE occurs worldwide and is generally fatal if left untreated.

DESCRIPTION

  • An infection of the valvular (primarily) and/or mural (rarely) endocardium
  • System(s) affected: cardiovascular, endocrine/metabolic, hematologic/lymphatic, immunologic, pulmonary, renal/urologic, skin/exocrine, neurologic
  • Synonym(s): bacterial endocarditis; subacute bacterial endocarditis (SBE); acute bacterial endocarditis (ABE)

EPIDEMIOLOGY

More common in males (range is 3:2 to 9:1). >50% of cases in the United States occur in individuals >60 years of age.

Incidence

  • Incidence at ~15 in 100,000, increasing from previous years
  • The predominant form of IE is community associated. Up to one-third of cases of are health care-acquired in resource-rich countries.
  • Increasing incidence of cardiovascular device-related infections due to a higher frequency of implantable devices
  • Can be community- or hospital-acquired
  • Most commonly affects the mitral valve and aortic valve (increased left-sided pressures and turbulent flow)

ETIOLOGY AND PATHOPHYSIOLOGY

IE is most commonly caused by a nonbacterial thrombus that adheres to an endocardial surface, coupled with a bacterial source sufficient to seed the thrombus. This can occur from direct bacterial invasion or valvular trauma:

  • Native valve endocarditis
    • Acute: Staphylococcus aureus (most common); Streptococcus groups A, B, C, G; Streptococcus pneumoniae; Staphylococcus lugdunensis; Enterococcus spp.; Haemophilus influenzae or parainfluenzae; Neisseria gonorrhoeae
    • Subacute: α-hemolytic streptococci, Streptococcus bovis, Enterococcus spp., S. aureus, Staphylococcus epidermidis; HACEK organisms
  • Intravenous drug abuse endocarditis (IVDA) (most commonly tricuspid valve): S. aureus, Enterococcus spp.; Pseudomonas aeruginosa, Burkholderia cepacia, other bacilli (gram-negative); Candida spp.
  • Prosthetic valve endocarditis
    • Early (≤12 months after valve implantation): S. aureus, S. epidermidis; gram-negative bacilli; Candida spp., Aspergillus spp.
    • Late (>12 months after valve implantation): α-hemolytic streptococci, S. aureus, Enterococcus spp., S. epidermidis, Candida spp., Aspergillus spp.
  • Culture-negative endocarditis: 10% of cases; Bartonella quintana (homeless); Brucella spp., fungi, Coxiella burnetii (Q fever), Chlamydia trachomatis, Chlamydophila psittaci, HACEK organisms
  • Device-related endocarditis: coagulase-negative staphylococci or S. aureus

RISK FACTORS

  • Injection drug use, IV catheterization, certain malignancies (colon cancer), poor dentition/infection, chronic hemodialysis, age >60 years, male sex, implantable devices
  • Highest risk with (1):
    • Previous IE
    • Prosthetic cardiac valves (including transcatheter-implanted prostheses and homografts)
    • Cardiac transplant with valvular regurgitation
    • Prosthetic material used for cardiac valve repair (such as annuloplasty rings or chords)
    • Congenital heart disease (CHD): unrepaired cyanotic CHD or repaired CHD residual shunts of valvular regurgitation at the site of or adjacent to the site of a prosthetic patch or prosthetic device

GENERAL PREVENTION

  • Good oral hygiene
  • Antibiotic prophylaxis is only recommended in patients with a high risk of adverse outcomes if IE were to occur—(see “High Risk Factors”). Administer 30 to 60 minutes prior to the procedure (exception vancomycin which should be administered 120 minutes prior to the procedure).
  • In high-risk patients, consider antibiotic prophylaxis for dental procedures that involve manipulation of gingival tissue, manipulation of the periapical region of teeth, or perforation of the oral mucosa.
  • Prophylaxis is not recommended for EGD, TEE, colonoscopy, or cystoscopy in absence of evidence for active/ongoing infection.

COMMONLY ASSOCIATED CONDITIONS

Most patients with IE have preexisting conditions (see “Risk Factors” above).

Descriptive text is not available for this image DIAGNOSIS

  • Modified Duke criteria [clinical criteria for IE (1): 2 major criteria, or 1 major and 3 minor criteria, or 5 minor criteria; possible IE: 1 major and 1 minor or 3 minor criteria; rejected diagnosis: firm alternative diagnosis explaining evidence of IE, or resolution of IE after ≤4 days with antibiotic therapy, or does not meet criteria for possible IE as seen above]
  • Major clinical criteria
    • Positive blood culture: isolation of typical microorganism for IE from two separate blood cultures or persistently positive blood culture
    • Single positive blood culture for C. burnetii or anti–phase-1 IgG antibody titer >1:800
    • Positive echocardiogram: presence of vegetation, abscess, or new partial dehiscence of prosthetic valve
    • New valvular regurgitation (change in preexisting murmur not sufficient)
  • Minor criteria
    • Predisposing heart condition or IV drug use
    • Fever ≥38°C (100.4°F)
    • Vascular phenomena: arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhage, Janeway lesions
    • Immunologic phenomena: glomerulonephritis, Osler nodes, Roth spots, rheumatoid factor (RF)
    • Microbiologic evidence

HISTORY

  • Fever (>38°C), chills, cough, dyspnea, orthopnea; especially in subacute endocarditis: night sweats, weight loss, fatigue
  • Review risk factors.
  • Symptoms of transient ischemic attack, cerebrovascular accident (CVA), or myocardial infarction (MI) on presentation

PHYSICAL EXAM

  • Most patients with IE have new murmur/change to an existing murmur. Signs of heart failure are common if valve function is compromised.
  • Peripheral stigmata of IE: splinter hemorrhages in fingernail beds, Osler nodes, Roth spots, Janeway lesions, palatal/conjunctival petechiae, splenomegaly, hematuria
  • Neurologic findings consistent with CVA

DIFFERENTIAL DIAGNOSIS

Vasculitis, temporal arteritis, fever of unknown origin, infected central venous catheter, marantic endocarditis, connective tissue diseases, intra-abdominal infections, rheumatic fever, salmonellosis, brucellosis, Lyme disease, malignancy, tuberculosis, atrial myxoma, septic thrombophlebitis

DIAGNOSTIC TESTS & INTERPRETATION

  • If not critically ill; three sets of blood cultures drawn >2 hours apart from different sites before administration of antibiotics with repeat cultures in 48 to 72 hours until bacterial clearance
  • If acutely ill, draw three sets of blood cultures over 1 hour prior to empiric therapy.
  • Leukocytosis; anemia; decreased C3, C4, CH50; and +RF in subacute endocarditis
  • ESR, C-reactive protein (CRP)
  • Hematuria
  • Consider serologies for Chlamydia, Q fever, Legionella, and Bartonella in “culture-negative” endocarditis.
  • Transthoracic (TTE) or transesophageal echocardiogram (TEE [preferred])
  • CT scan

Initial Tests (lab, imaging)

Routine laboratory findings are often nonspecific and often are a manifestation of secondary sequelae of IE.

  • Laboratory findings:
    • Nonspecific
      • Elevated inflammatory markers; leukocytosis, +RF; normochromic normocytic anemia
    • Findings related to secondary system involvement
      • RBC casts; microscopic hematuria, proteinuria, pyuria
  • Imaging
    • ECG: New/evolving signs of conduction disease (atrioventricular blocks and/or bundle branch blocks) are often a sign of paravalvular and/or myocardial involvement.
    • TTE/TEE: new or worsening valvular regurgitation, new partial dehiscence of prosthetic valve, new intracardiac shunting, presence of vegetations

Follow-Up Tests & Special Considerations

If indicated, follow-up imaging to evaluate for secondary system involvement or to rule out other causes:

  • Chest x-ray: may reveal evidence of septic pulmonary embolism or signs of congestive heart failure
  • CT chest/abdomen/pelvis: Evaluate distal sites of infections and/or infarction.

Descriptive text is not available for this image TREATMENT

GENERAL MEASURES

In general, antibiotic therapy for IE should be targeted to the organism isolated from blood cultures. The duration of therapy should be calculated from the first day of the negative blood cultures.

MEDICATION

First Line

  • Start empiric treatment after three sets of blood cultures have been drawn. Results guide treatment.
    • Native valves: ampicillin-sulbactam IV with gentamicin IV/IM; if penicillin-allergic, use vancomycin IV with gentamicin IV/IM and with ciprofloxacin PO/IV.
    • Prosthetic valves: vancomycin IV with gentamicin IV/IM and rifampin PO, if <12 months postsurgery; if >12 months, use native valve regimen.
  • Penicillin-susceptible viridans streptococci or Streptococcus bovis
    • Native valve: penicillin G IV continuously or ceftriaxone IV/IM for 4 weeks
    • Prosthetic valve: penicillin G IV for 6 weeks or ceftriaxone IV/IM ± gentamicin IV/IM for 2 weeks
  • Penicillin-resistant viridans streptococci or Streptococcus bovis
    • Native valve: penicillin G IV + gentamicin IV/IM
    • Prosthetic valve: penicillin G IV or ceftriaxone IV/IM for 6 weeks + gentamicin IV/IM for 2 weeks
  • Penicillin-susceptible staphylococcus
    • Native valve: oxacillin or nafcillin IV for 6 weeks. For oxacillin-resistant strains, use vancomycin IV for 6 weeks.
    • Prosthetic valve: oxacillin or nafcillin IV + rifampin IV/PO for 6 weeks, + gentamicin IV for first 2 weeks. For oxacillin-resistant strains, use vancomycin IV, + rifampin IV/PO, both for 6 weeks, + gentamicin IV/IM for the first 2 weeks.
  • Penicillin-resistant Staphylococcus
    • Native valve: vancomycin for 6 weeks or daptomycin IV for 6 weeks
    • Prosthetic valve: vancomycin + rifampin IV/PO + gentamicin IV/IM for 2 weeks
  • Penicillin-sensitive Enterococcus
    • Native or prosthetic valve: ampicillin IV or penicillin G IV + gentamicin IV for 4 to 6 weeks
  • HACEK organisms: ceftriaxone IM or IV for 4 weeks or ampicillin-sulbactam IV for 4 weeks or ciprofloxacin PO or IV for 4 weeks

SURGERY/OTHER PROCEDURES

Surgery is required in 50% of IE cases; indications:

  • Heart failure due to aortic or mitral valve disease
    • Prevention of embolism: aortic or mitral valve vegetations >10 mm with prior embolic episodes; isolated very large vegetation >15 mm; in patients with major ischemic stroke, surgery is delayed for at least 4 weeks, if possible.
  • Uncontrolled infection: persistent fever and positive cultures >7 to 10 days; infection caused by fungi or resistant organism; presence of abscess, fistula, false aneurysm, or enlarging vegetations
  • Early prosthetic valve IE

Descriptive text is not available for this image ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

Patient Monitoring

  • Baseline ECG; monitor ECG for conduction disturbances/MI in initial weeks of therapy.
  • TTE at the conclusion of therapy
  • Blood cultures q48h until negative

PROGNOSIS

The 1-year mortality of IE is 30%. Late complications contribute to poor prognosis. These include heart failure, reinfection, and cerebral emboli. The 10-year survival is 60–90%.

COMPLICATIONS

  • Cerebral complications are the most frequent and severe, occurring in 15–20% of patients. Neurologic events are the most frequent complications in patients with IE requiring ICU admission. Ischemic stroke is the presenting symptom of IE in 20% of cases.
  • Emboli: arterial, infectious (e.g., abscesses of heart, lung, brain, meninges, bone, pericardium)
  • Inflammatory/immune disorders (e.g., arthritis, myositis, glomerulonephritis)
  • Other complications: congestive heart failure, ruptured valve cusp, sinus of Valsalva aneurysm, arrhythmia, and mycotic aneurysms

Authors

Theodore B. Flaum, DO
Kaitlin Unser, DO

REFERENCE

  1. Miao H, Zhang Y, Zhang Y, et al. Update on the epidemiology, diagnosis, and management of infective endocarditis: a review. Trends Cardiovasc Med. 2024;34(8):499–506. doi:10.1016/j.tcm.2024.01.001  [PMID:38199513]

ADDITIONAL READING

  • Fowler VG, Durack DT, Selton-Suty C, et al. The 2023 Duke-International Society for Cardiovascular Infectious Diseases criteria for infective endocarditis: updating the modified Duke criteria. Clin Infect Diseases. 2023;77(4):518–526. doi:10.1093/cid/ciad271.  [PMID:37138445]
  • Patel SK, Hassan SMA, Côté M, et al. Current trends and challenges in infective endocarditis [published online ahead of print November 8, 2024]. Curr Opin Cardiol. doi:10.1097/HCO.0000000000001192.  [PMID:39513568]

Descriptive text is not available for this image CODES

ICD10

  • I33.0 Acute and subacute infective endocarditis
  • I39 Endocarditis and heart valve disord in dis classd elswhr
  • A54.83 Gonococcal heart infection
  • B37.6 Candidal endocarditis

SNOMED

  • 233850007 infective endocarditis (disorder)
  • 301183007 Bacterial endocarditis (disorder)
  • 61048000 Gonococcal endocarditis (disorder)
  • 63553008 Candidal endocarditis (disorder)
  • 73028002 staphylococcal endocarditis (disorder)
  • 459056003 Acute infective endocarditis (disorder)

CLINICAL PEARLS

  • Preprocedural antibiotic prophylaxis is recommended for patients with artificial heart valves, a previous history of IE, CHD, and cardiac transplants with valvulopathy.
  • TEE/TTE and blood cultures are the mainstays for diagnosing IE.
  • The most commonly identified organisms are viridans Streptococcus spp. and Staphylococcus.
  • Valves most commonly involved: (i) mitral valve, (ii) aortic valve, (iii) combination of aortic and mitral valves, (iv) tricuspid valve, (v) pulmonic valve

Last Updated: 2026

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