Infective Endocarditis

Definition

IE = microbial invasion of heart valves/mural endocardium. Vegetations = platelets + fibrin + organism microcolonies + inflammatory cells. Sites: heart valves > VSD low-pressure side > mural endocardium.

Acute vs Subacute

Pathogenesis (5 steps)

1. Risk factors — cardiac defect (MR, AS, AR, VSD), IV catheter, prosthetic valve surgery
2. Endothelial injury — turbulent flow/catheter trauma → damage → NBTE (nonbacterial thrombotic endocarditis, sterile platelet-fibrin deposit)
3. Colonization — transient bacteremia (dental work/brushing) seeds the thrombus
4. Vegetation formation — fibrin+platelet cover protects organism, multiplication continues
5. Metastasis — seeds bacteria into blood steadily + emboli to distant sites

Etiology — Entry Portal

Viridans strep = oral cavity. Staph = skin. HACEK = URT. S. gallolyticus/enterococci = GIT.

By context:

• Native valve: S. aureus overall (community = viridans strep; healthcare-associated = S. aureus)
• Prosthetic valve: Early (<12mo, nosocomial) = CoNS + S. aureus. Late (>12mo, community) = viridans strep. OVERALL = CoNS (68-85%, mostly MRSA)
• IV drug abuser: Right-sided (tricuspid) = S. aureus (mostly MRSA). Left-sided (mitral) = varied (Enterococcus, S. aureus, Pseudomonas, Candida, Bacillus/Lactobacillus/Corynebacterium). Overall = S. aureus
• Subacute: viridans streptococci
• Culture-negative (5-10%): 1/3-1/2 = prior antibiotics. Rest = fastidious (nutritionally variant strep, HACEK, Coxiella burnetii, Bartonella, Brucella, Tropheryma whipplei-indolent afebrile). Geographic clustering: Coxiella/Bartonella=Europe, Brucella=Middle East.

Clinical Manifestations

Cardiac: new/worsening regurgitant murmur (useful esp. on normal valve). Noncardiac: fever, chills, sweats, anorexia, weight loss, myalgia, arthralgia, arterial emboli, splenomegaly, clubbing, petechiae, neuro signs, peripheral stigmata (Osler’s nodes, subungual hemorrhage, Janeway lesions). Lab: anemia, leukocytosis, microscopic hematuria, ↑ESR/CRP, +RA factor.

S. aureus IE: LARGER vegetations (>10mm) → MORE septic embolization. Mitral valve = higher embolization risk. Cerebrovascular emboli → stroke/encephalopathy.

Diagnosis — Modified Duke Criteria

Major:

1. Positive blood culture — typical organism (viridans strep, S. gallolyticus, HACEK, S. aureus, enterococci) × 2 separate cultures; OR persistent atypical agent (>12h apart, or majority of ≥4 sets ≥1h apart); OR single + culture Coxiella burnetii or phase I IgG >1:800
2. Endocardial involvement — +echo (oscillating mass, abscess, new partial prosthetic dehiscence) OR new valvular regurgitation

Minor: predisposing condition/IVDU; fever ≥38.0°C; vascular phenomena (major emboli, septic pulmonary infarct, mycotic aneurysm, ICH, conjunctival hemorrhage, Janeway lesions); immunologic phenomena (GN, Osler’s nodes, Roth spots, RA factor); microbiologic evidence not meeting major.

Definite IE = 2 major, OR 1 major+3 minor, OR 5 minor.

Blood culture: 2 sets >12h apart, OR 3 sets over 1hr (30min gaps), different venipuncture sites, BEFORE antibiotics.

Non-blood-culture tests: serology (Brucella, Bartonella, Legionella, C. psittaci, C. burnetii), vegetation culture/special stain (PAS = T. whipplei), DFA, 16S rRNA PCR+sequencing.

Echo: confirms anatomy, sizes vegetations, detects complications, assesses cardiac function.

Specific Organisms

Staph endocarditis: S. aureus = leading cause, acute course, large vegetations, high embolization. CoNS (S. epidermidis) ↑prosthetic valve IE, mostly MRSA.

Viridans strep: oral/URT commensal → transient bacteremia (chewing/brushing/dental) → subacute IE on damaged valve. Also: dental caries (S. mutans, glucosyltransferase → acid+dextran plaque), neutropenic cancer bacteremia. S. milleri group (intermedius/anginosus/constellatus) → suppurative infection (brain abscess, empyema), NOT endocarditis pattern. Lab: Gram+ cocci long chains, minute α-hemolytic green colonies (“viridans”=green). Differs from pneumococcus: optochin RESISTANT, bile INSOLUBLE. Rx: penicillin (vancomycin if neutropenic bacteremia).

Nutritionally variant strep (Abiotrophia, Granulicatella): needs pyridoxal (B6). Fails plain subculture, grows as SATELLITE colonies near helper bacteria (e.g. S. aureus) = “satelliting streptococci.” Catalase-negative, short chains. Rx: penicillin+gentamicin.

S. gallolyticus (ex-S. bovis): group D strep, animal gut commensal. Bacteremia + subacute IE. LINKED TO COLORECTAL CANCER/polyps. Rx: penicillin.

HACEK: H. parainfluenzae, Aggregatibacter actinomycetemcomitans/aphrophilus/paraphrophilus, Cardiobacterium hominis, Eikenella corrodens, Kingella kingae. Fastidious, slow, capnophilic Gram-negative oral commensals. 3% of IE. Subacute, preexisting valve defect/dental work, aortic+mitral valve.

• H. parainfluenzae: needs only factor X (not V, unlike H. influenzae)
• A. actinomycetemcomitans: commonest HACEK IE cause
• Eikenella corrodens: pitting/corroded colonies on blood agar Diagnosis: prolonged incubation (up to 1wk), 5-10% CO2. Rx: ceftriaxone DOC (ampicillin for Eikenella), quinolones if β-lactamase+. Good prognosis.

Treatment

S. aureus native valve: MSSA=cloxacillin/nafcillin 6wk. MRSA=vancomycin 6wk. Prosthetic: + rifampin(6wk) + gentamicin(2wk). Viridans strep/S. gallolyticus native: penicillin/ceftriaxone 4wk. Prosthetic: + gentamicin, total 6wk. HACEK: ceftriaxone/ciprofloxacin 4wk (6wk prosthetic).

TDM: Vancomycin trough 15-20 μg/mL (avoid if MIC>1). Gentamicin (synergy) peak <4 μg/mL, trough <1 μg/mL.

Other CVS Infections

Myocarditis: chest pain, arrhythmia, HF. Viral (Coxsackie B most common, adenovirus, parvovirus B19, HHV-6, dengue), T. cruzi (Chagas), rarely bacterial. Pericarditis: chest pain, friction rub, effusion. Viral (Coxsackie B commonest), rare bacterial (pneumonia complication), M. tuberculosis (TB complication). Pericardial effusion: secondary to pericarditis/malignancy/autoimmune. Mycotic aneurysm: ANY infectious cause (not literally fungal) of arterial wall weakening, EXCLUDES syphilitic aortitis. Infective endarteritis: arterial wall inflammation ± aneurysm. Suppurative thrombophlebitis: vein wall inflammation, usually IV catheter. S. aureus, Enterobacteriaceae, yeasts. Lemierre’s syndrome: internal jugular vein thrombophlebitis + bacteremia. Fusobacterium necrophorum (anaerobe), post-oropharyngeal infection.

What Infective Endocarditis Is

Infective endocarditis (IE) is microbial invasion of the heart valves or the mural endocardium, producing bulky, friable vegetations — masses of platelets, fibrin, microcolonies of the causative organism, and scattered inflammatory cells. Vegetations settle most often on the heart valves, followed by the low-pressure side of a ventricular septal defect, and on the mural endocardium itself.

Acute versus Subacute

The two forms differ across nearly every axis that matters clinically:

Pathogenesis

IE develops through a defined sequence, and every step is a point where prevention could plausibly intervene:

1. Underlying risk factors — a predisposing cardiac defect (mitral regurgitation, aortic stenosis/regurgitation, ventricular septal defect), an indwelling IV catheter, or prosthetic valve surgery.
2. Endothelial injury — intact endothelium resists both bacterial infection and thrombus formation, so IE, though it can affect a normal valve, occurs far more readily on a damaged one: turbulent flow across a defective valve, or direct trauma from an IV catheter, injures the endothelium. This injury triggers deposition of platelets and fibrin — nonbacterial thrombotic endocarditis (NBTE) — a sterile precursor lesion.
3. Colonization — the resulting thrombus becomes a site for bacterial attachment during a transient bacteremia (dental work, tooth brushing, even chewing can release organisms briefly into the blood).
4. Vegetation formation — the colonized surface is rapidly covered by more fibrin and platelets, protecting the organisms from host defenses and antibiotics while they multiply — the vegetation itself.
5. Metastasis — the vegetation continuously seeds bacteria into the blood at a slow, steady rate, and can also embolize to distant sites.

Etiological Agents

Different organisms enter via different portals: viridans streptococci from the oral cavity, staphylococci from skin, HACEK organisms from the upper respiratory tract, and Streptococcus gallolyticus/enterococci from the GI tract.

By clinical context:

• Native valve IE: S. aureus overall (community-acquired cases favour viridans streptococci; healthcare-associated cases favour S. aureus).
• Prosthetic valve IE: early (within 12 months of surgery, usually nosocomial, from intraoperative contamination) is dominated by coagulase-negative staphylococci and S. aureus; late (after 12 months, usually community-acquired) by viridans streptococci; but overall, regardless of timing, CoNS remain the most common agent (68–85%), mostly methicillin-resistant.
• IV drug abusers: right-sided (tricuspid) IE is overwhelmingly S. aureus (mostly MRSA); left-sided (mitral) IE has a more varied etiology — enterococcus and S. aureus predominate, but Pseudomonas aeruginosa, Candida, and unusual organisms (Bacillus, Lactobacillus, Corynebacterium) also occur. Overall, S. aureus remains commonest.
• Subacute endocarditis: viridans streptococci.
• Culture-negative endocarditis (5–10% of IE): one-third to half is from prior antibiotic exposure; the rest from fastidious organisms — nutritionally variant streptococci, HACEK organisms, Coxiella burnetii, Bartonella, Brucella, and Tropheryma whipplei (which causes an indolent, culture-negative, afebrile endocarditis). Some of these cluster geographically (Coxiella/Bartonella in Europe, Brucella in the Middle East).

Clinical Manifestations

Cardiac: a new or worsening regurgitant murmur — especially useful when it appears on a previously normal valve.

Noncardiac: fever, chills, sweats, anorexia, weight loss, myalgia, arthralgia, arterial emboli, splenomegaly, clubbing, petechiae, neurologic manifestations, and the classic peripheral stigmata — Osler’s nodes, subungual hemorrhages, Janeway lesions.

Laboratory: anaemia, leucocytosis, microscopic hematuria, raised ESR/CRP, positive rheumatoid factor.

S. aureus IE specifically tends to produce larger vegetations (>10 mm), correspondingly more frequent septic embolization, and a higher risk of embolization from mitral valve involvement specifically, including cerebrovascular emboli causing stroke or encephalopathy.

Diagnosis: Modified Duke Criteria

Diagnosis rests on the modified Duke criteria, combining clinical, laboratory, and echocardiographic evidence.

Major criteria:

1. Positive blood culture — a typical IE organism (viridans streptococci, S. gallolyticus, HACEK group, S. aureus, or enterococci) from two separate cultures; OR persistently positive cultures with an atypical agent (sets drawn >12h apart, or majority of ≥4 sets with first and last ≥1h apart); OR a single positive culture for Coxiella burnetii, or phase I IgG titre >1:800.
2. Evidence of endocardial involvement — a positive echocardiogram (oscillating intracardiac mass, abscess, or new partial prosthetic-valve dehiscence) or new valvular regurgitation.

Minor criteria: predisposing heart condition or IV drug use; fever ≥38.0°C; vascular phenomena (major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial haemorrhage, conjunctival haemorrhages, Janeway lesions); immunologic phenomena (glomerulonephritis, Osler’s nodes, Roth spots, rheumatoid factor); microbiologic evidence not meeting the major criterion.

Definite endocarditis requires 2 major, or 1 major + 3 minor, or 5 minor criteria.

Blood culture technique: two sets collected >12h apart, or three sets over one hour (30-minute gaps), each set from a different venipuncture site, collected before antibiotics wherever possible.

Non-blood-culture tests fill the gap for fastidious agents: serology (Brucella, Bartonella, Legionella, Chlamydophila psittaci, Coxiella burnetii), culture or special stains of excised vegetations (PAS for Tropheryma whipplei), direct fluorescent antibody, and broad-range 16S rRNA PCR with sequencing.

Echocardiography confirms the anatomic diagnosis, sizes vegetations, detects intracardiac complications, and assesses cardiac function.

Specific Organisms

Staphylococcal endocarditis: S. aureus is the leading overall cause and usually runs an acute course, with the larger-vegetation, higher-embolization pattern described above. Coagulase-negative staphylococci (S. epidermidis) increasingly cause prosthetic-valve IE, mostly methicillin-resistant.

Viridans streptococci: oral/upper-respiratory commensals, normally harmless, but a transient bacteremia from chewing, brushing, or dental procedures lets them seed a damaged valve — the classic cause of subacute bacterial endocarditis. The same organisms cause dental caries (S. mutans, breaking down sucrose via glucosyltransferase into acid and adhesive dextran that forms plaque) and prolonged bacteremia in neutropenic cancer patients. The S. milleri group (S. intermedius, S. anginosus, S. constellatus) instead causes suppurative infections — brain abscess, empyema. Diagnostically: Gram-positive cocci in long chains, minute α-hemolytic green colonies on blood agar (hence “viridans” = green), differentiated from pneumococcus by optochin resistance and bile insolubility. Usually penicillin-sensitive except in neutropenic bacteremia, where vancomycin is preferred.

Nutritionally variant streptococci (Abiotrophia, Granulicatella): require pyridoxal (vitamin B6) for growth; fail on ordinary subculture but grow as satellite colonies near a “helper” organism like S. aureus — hence “satelliting streptococci.” Catalase-negative, Gram-positive cocci in short chains. Treated with penicillin plus gentamicin.

S. gallolyticus (formerly S. bovis): a group D streptococcus, animal-gut commensal, occasionally causing bacteremia and subacute endocarditis, notably associated with colorectal cancer/polyps — a finding that should prompt colonoscopy. Penicillin is the drug of choice.

HACEK organisms: Haemophilus parainfluenzae, Aggregatibacter actinomycetemcomitans, A. aphrophilus, A. paraphrophilus, Cardiobacterium hominis, Eikenella corrodens, Kingella kingae — fastidious, slow-growing, capnophilic Gram-negative oral commensals accounting for 3% of IE, typically subacute, in patients with preexisting valve defects or recent dental work, most often affecting the aortic and mitral valves. Individually: H. parainfluenzae differs from H. influenzae by needing only factor X (not V); A. actinomycetemcomitans is the commonest HACEK cause of IE; Eikenella corrodens produces characteristic pitting/corroded colonies on blood agar. Diagnosis needs prolonged incubation (up to a week) in 5–10% CO₂; ceftriaxone is the drug of choice (ampicillin for Eikenella), with quinolones reserved for β-lactamase producers. Prognosis is good.

Treatment

Regimens are organism- and valve-specific: S. aureus MSSA gets cloxacillin/nafcillin, MRSA gets vancomycin, both for 6 weeks (native valve), with rifampin (6 weeks) and gentamicin (2 weeks) added for prosthetic-valve IE. Viridans streptococci/S. gallolyticus get penicillin or ceftriaxone for 4 weeks (native valve), with gentamicin added for 6 weeks in prosthetic-valve disease. HACEK gets ceftriaxone or ciprofloxacin for 4 weeks (6 for prosthetic valve). Therapeutic drug monitoring matters for both vancomycin (target trough 15–20 μg/mL, avoided if MIC >1 μg/mL) and gentamicin (used for synergy, peak <4 μg/mL, trough <1 μg/mL).

Other Infections of the Cardiovascular System

Beyond the endocardium, the same broad organism pool can infect other cardiac layers and blood vessels: myocarditis (chest pain, arrhythmia, heart failure — mostly viral: Coxsackievirus B, adenoviruses, parvovirus B19, HHV-6, dengue; also Trypanosoma cruzi in Chagas disease; rarely bacterial), pericarditis (chest pain, friction rub, effusion — mostly viral, Coxsackievirus B commonest; rarely bacterial as a pneumonia complication; M. tuberculosis as a TB complication), and pericardial effusion (excess pericardial fluid, usually secondary to pericarditis, malignancy, or autoimmune disease). Vascular infections include mycotic aneurysm (any infectious — not literally fungal — cause of arterial-wall weakening and bulging, excluding syphilitic aortitis) and infective endarteritis (arterial wall inflammation, with or without aneurysm). Device-related vascular infections include CRBSI (covered under Hospital Acquired Infections) and suppurative thrombophlebitis — vein-wall inflammation, most often from an indwelling IV catheter, caused by S. aureus, Enterobacteriaceae, or yeasts; Lemierre’s syndrome is the specific variant of internal jugular vein thrombophlebitis with bacteremia caused by the anaerobe Fusobacterium necrophorum, following an oropharyngeal infection.

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