Symptoms

• Moderate & remitting fever is the most common symptom
• Anorexia, wt loss, malaise & night sweats
• Fatigue, diaphoresis, chills, N/V, arthralgia, myalgia

• Heart murmur consistent w/ valvular regurgitation
• Petechiae on the skin, conjunctivae or oral mucosa
• Osler’s nodes: Red, painful, indurated lesions, 2-15 mm in diameter seen on the palms or soles & usually in the digital phalanges
• Janeway lesions: Non-tender, erythematous macules that appear on the palms or soles
• “Blue toe syndrome”: Embolization of small vegetation fragments
• Roth’s spots: Red, retinal hemorrhages w/ a pale center
• Splenomegaly
• Signs of CHF

• Most important lab test
• At least 3 BCs should be taken as soon as possible at 30-min intervals
  • Delaying blood sampling to coincide w/ peaks of fever is unnecessary
• It is recommended to postpone antimicrobial therapy until BCs become positive (unless the patient is septic)
• If antimicrobial therapy has been started, wait for at least 3 days after discontinuing short-term antibiotic treatment before taking BC
  • If patient has been on long-term antibiotic treatment, positive BCs may not appear until after 6-7 days w/o antibiotic
• Identification of causative organism should be up to species level

• CBC w/ differential
  • Many patients have leukocytosis: 15,000-25,000/microlitre w/ a left shift
  • Anemia is common: Normocytic & normochromic w/ low serum Fe level & TIBC
• Serum electrolytes
  • Some patients may have elevated serum creatinine
• Urinalysis: May reveal microscopic hematuria, pyuria, RBC casts, bacteriuria, proteinuria
• ESR: Elevated in most cases
• C-reactive protein level: Elevated
• Rheumatoid factor: Elevated in approx half of the presenting patients

• Diagnostic test of choice in detecting vegetations in cardiac valves

• Mobile, echodense mass attached to the valvular or the mural endocardium esp if present on the preferred locations, or attached to implanted prosthetic material w/ no alternative anatomical explanation
• Demonstration of abscesses or fistulas
• A new dehiscence of a valvular prosthesis esp when occurring late after implantation

• Vegetation appears as a discrete mobile echogenic mass attached to the valvular surface downstream from a high- to low-pressure chamber
• Vegetations ≥2 mm may be visualized; the larger the size, the more likely a vegetation will be detected
• TTE detection rate is 40-63% in patients w/ clinically suspected IE
• If the clinical suspicion of IE is low, the TTE is of good quality & the result is negative, endocarditis is unlikely

• Has superior resolution, thus carries a greater sensitivity (90-100%) in detecting vegetations as compared w/ TTE
• If suspicion of IE is high (eg staphylococcal bacteremia), then TEE should be performed in all negative TTE cases
• TEE should be performed in all suspected PVE cases, in cases of aortic location, prior to cardiac surgery during active IE, & when intracardiac device leads are present
• If TEE is negative but suspicion of IE remains, repeat TEE after 7-10 days, or earlier if Staphylococcus aureus infection is suspected

Other Diagnostic Studies

• May be taken upon admission in patients w/ suspected acute IE
  • Evidence of low septal abscesses w/ involvement of the intraventricular conduction system is detected on ECG
  • Can be used to rule out conduction abnormalities & to establish baseline

• May delineate the presence of CHF
• May show septic pulmonary emboli & infiltrates w/ cavitation that are associated w/ right-sided IE

• Obtain in any patient w/ neurologic signs & symptoms
• Multislice CT is useful in evaluating IE-associated valvular abnormalities eg perivalvular extent of abscess, pseudoaneurysm

MODIFIED DUKE CLINICAL CRITERIA FOR DIAGNOSIS OF IE

Definite IE

• Microorganisms demonstrated by culture or histologic exam of a vegetation, a vegetation that has embolized, or an intracardiac abscess; or
• Pathological lesions: Vegetation or intracardiac abscess is present & confirmed by histology showing active endocarditis

• 2 major criteria; or
• 1 major criterion + 3 minor criteria; or
• 5 minor criteria

• 1 major criterion + 1 minor criterion; or
• 3 minor criteria

• Firm alternate diagnosis for manifestations of endocarditis
• Resolution of manifestations of endocarditis w/ antibiotic therapy for ≤4 days; or
• No pathological evidence of IE at surgery or autopsy, after antibiotic therapy for ≤4 days; or
• Does not meet the criteria for possible IE, as above

DEFINITIONS OF TERMS USED IN THE DUKE CRITERIA FOR THE DIAGNOSIS OF IE

• Positive blood culture for IE
  • Typical microorganism consistent w/ IE from 2 separate BCs as noted below:
    • Viridans streptococci, Streptococcus bovis, HACEK group, or Staphylococcus aureus
    • Community-acquired enterococci in the absence of a primary focus; or
  • Microorganisms consistent w/ IE from persistently positive BCs defined as
    • ≥2 positive cultures of blood samples drawn >12 hr apart; or
    • All of 3 or a majority of ≥4 separate cultures of blood (w/ 1st & last sample drawn ≥1 hr apart)
  • Single positive BC for Coxiella burnetii or antiphase I IgG antibody titer >1:800

• Evidence of endocardial involvement

• Positive echocardiogram for IE [TEE recommended in patients w/ prosthetic valves & rated at least “possible IE” by clinical criteria, or complicated IE (paravalvular abscess); TTE as 1st test in other patients] defined as:
  • Oscillating intracardiac mass on valve or supporting structures, in the path of regurgitant jets, or on implanted material in the absence of an alternative anatomic explanation; or
  • Abscess; or
  • New partial dehiscence of prosthetic valve, or
• New valvular regurgitation (worsening or changing of preexisting murmur not sufficient)

• Predisposition: Predisposing heart condition or IV drug use
• Fever: Temp ≥38˚C
• Vascular phenomena: Major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages & Janeway lesions
• Immunologic phenomena: Glomerulonephritis, Osler’s nodes, Roth spots & rheumatoid factor
• Microbiological evidence: Positive BC but does not meet a major criterion as noted above or serological evidence of active infection w/ organism consistent w/ IE

Adapted from references: Li JS, Sexton DJ, Mick N, et al. Proposed modifications to the Duke Criteria for the diagnosis of infective endocarditis. Clin Infect Dis. 2000;30:633-8; and Durack DT, Lukes AS, Bright DK. New criteria for diagnosis of infective endocarditis: Utilization of specific endocardiographic findings. Duke Endocarditis Service. Am J Med. 1994;96:200-9.

Etiology

• Staphylococcus sp: Causes approx 25% of NVE
  • S aureus (coagulase-positive staphylococci): Commonly cause PVE, IE in IV drug abusers (IVDA) & in patients w/ previously normal cardiac valves
  • IVDA often present w/ right-sided cardiac involvement
  • Non-IVDA usually present w/ left-sided cardiac involvement & have skin & soft tissue infections w/ underlying congenital abnormalities
  • S epidermidis, S lugdunensis (coagulase-negative staphylococci): Most common causes of PVE & have been known to cause NVE
  • Methicillin-susceptible S aureus (MSSA): May cause right-sided endocarditis in IV drug users
  • Methicillin-resistant S aureus (MRSA): Occurs particularly in PVE, right-sided endocarditis in IV drug users & nosocomial endocarditis
• Streptococcus sp (viridans group of streptococci; S pneumoniae; S pyogenes; Lancefield group B, C, G streptococci; S bovis, S mitis, S mutans, S sanguis & Abiotrophia sp): Most common causes of NVE
  • Group B streptococci: Most common β-hemolytic streptococci & cause the most virulent IE among streptococci which is characterized by a fulminant disease w/ large crumbling vegetations w/ the frequency of embolization related to size
  • Group G streptococci: Both native & prosthetic valves can be affected w/ left-sided involvement being more common
  • Viridans streptococci: Most common cause of NVE in patients w/ congenital heart disease or defects & in patients who are not IV drug users
  • S bovis: Also causes bacterial endocarditis
• Enterococci
• Culture-negative organisms: Common causative organisms of endocarditis producing culture-negative BCs
  • HACEK (Haemophilus parainfluenzae, aphrophilus, & paraphrophilus; Aggregatibacter (formerly Actinobacillus) actinomycetemcomitans; Cardiobacterium hominis, Eikenella corrodens; & Kingella): Can cause NVE & PVE
  • Bartonella henselae: Exposure to infected cats may predispose patient to IE
  • Brucella
  • Chlamydia psittaci: Exposure to infected birds may predispose patient to IE
  • Coxiella burnetii: Exposure to infected sheep, cattle & wild rabbits may predispose patient to IE
  • Legionella
    • Characterized by a febrile course that extends up to mth w/ cardiac signs of newly developed murmurs & extremely high anti-Legionella titers
  • Mycobacterium
  • Pseudomonas aeruginosa: Most commonly occurs in IVDAs & is an important pathogen in early PVE
    • Commonly involves the tricuspid valve & may present as subacute infection w/ septic pulmonary emboli & right-sided HF

Fungal

• Candida
• Aspergillus
• Nocardia

• Diagnose & treat patient appropriately for other disease states (eg atrial myxoma, SLE w/ marantic endocarditis, acute rheumatic fever & cardiac syndrome) presenting w/ similar signs & symptoms

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