Cardiovascular

Infective endocarditis: Duke criteria and diagnostic approach

Clinical Overview and When to Suspect Infective Endocarditis

— Aging population with degenerative valve disease

— Expanding prosthetic valves and cardiac implantable electronic devices (CIEDs)

— Injection drug use (IDU) epidemic — now a dominant driver in adults <40, classically right-sided (tricuspid)

— Healthcare-associated bacteremia (hemodialysis catheters, central lines)

— Fever + new or changing murmur

— Fever + known valvulopathy, prosthetic valve, or prior IE

— Persistent bacteremia (especially S. aureus, viridans strep, enterococci, HACEK, S. gallolyticus)

— Embolic phenomena: stroke in a young patient, splenic/renal infarcts, septic pulmonary emboli

— Unexplained heart failure in a febrile patient

— IDU with fever — empirically treat as IE until proven otherwise

— New conduction block (PR prolongation, AV block) in febrile patient → perivalvular abscess

Board pearl: S. gallolyticus (formerly S. bovis) bacteremia/IE mandates colonoscopy to evaluate for colorectal neoplasia — a classic Step 3 longitudinal follow-up question.

Key distinction: Fever + murmur ≠ automatic IE, but fever + S. aureus bacteremia should prompt TTE in every patient and TEE if high pretest probability, prosthetic valve, or inadequate TTE windows.

Definition: Microbial infection of the endocardial surface, most commonly involving native or prosthetic valves, but also chordae, mural endocardium, septal defects, and intracardiac devices (pacemaker/ICD leads, LVADs).

Epidemiology shift (US): Incidence ~15/100,000/year and rising, driven by:

When to suspect IE — trigger phrases on Step 3 stems:

Why it matters on Step 3: You are expected to operationalize the modified Duke criteria, order the right cultures and echo, choose empiric therapy, and orchestrate ID, cardiology, and cardiac surgery consults — often in a CCS case that evolves over days.

Presentation Patterns and Key History

— Low-grade fever, night sweats, weight loss, fatigue, anorexia

— Easily mistaken for malignancy, TB, connective tissue disease, or "FUO"

— Dental work, poor dentition, or recent GU/GI instrumentation in the history

— S. aureus is the canonical organism; destroys normal valves

— Common in IDU, hemodialysis, indwelling lines, post-op patients

— Heart failure may develop within days from valve destruction

— Early PVE (<1 year post-op): Coagulase-negative staph (S. epidermidis), S. aureus, gram-negatives, Candida — nosocomially seeded

— Late PVE (>1 year): Resembles native valve flora (viridans strep, enterococci, S. aureus)

— Prior IE, congenital heart disease, rheumatic disease, prosthetic valves, CIEDs

— Recent dental, GU, GI, or skin procedures

— IDU, central venous access, hemodialysis

— Immunosuppression, HIV status, malignancy

— Travel and animal exposures (Bartonella, Coxiella burnetii — Q fever from livestock/parturient animals, Brucella)

Step 3 management: A homeless patient with IDU presenting with fever and hemoptysis — order blood cultures × 3 from separate sites before antibiotics, CXR, CT chest looking for septic emboli, and TTE; do not delay empiric vancomycin while awaiting echo.

Board pearl: New splenomegaly + anemia + low-grade fever in a patient with bad dentition = think subacute viridans IE.

Subacute IE (weeks to months): Indolent course classically from viridans streptococci or HACEK organisms on previously abnormal valves.

Acute IE (days): Rapidly progressive, high fevers, rigors, sepsis physiology.

Prosthetic valve endocarditis (PVE) timing:

Right-sided IE (IDU): Fever + septic pulmonary emboli (pleuritic chest pain, hemoptysis, multiple nodular/cavitary lung lesions on CT) — murmur may be absent or soft tricuspid regurgitation.

Targeted history must capture:

Culture-negative IE (~10%): Recent antibiotic exposure, fastidious organisms (HACEK, Bartonella, Coxiella, Tropheryma whipplei, fungi). Ask specifically about prior outpatient antibiotics — the most common cause of culture-negative IE.

Physical Exam Findings and Hemodynamic Assessment

— Fever (>90% of cases), tachycardia, widened pulse pressure if severe AR

— Hypotension and end-organ hypoperfusion → cardiogenic vs septic shock; both can coexist

— New or changing regurgitant murmur — most often mitral or aortic regurgitation; tricuspid in right-sided/IDU IE

— Listen for an Austin Flint murmur, S3 (volume overload), or muffled prosthetic clicks (PVE dehiscence)

— Rales, elevated JVP, peripheral edema → acute decompensated heart failure from valve destruction (Class I indication for surgery)

— Janeway lesions: Painless, erythematous macules on palms/soles — embolic/septic

— Osler nodes: Painful, tender nodules on finger/toe pads — immune complex

— Roth spots: Retinal hemorrhages with pale centers

— Splinter hemorrhages: Subungual linear streaks

— Petechiae: Conjunctiva, palate, extremities

— Focal neurologic deficits (mycotic aneurysm rupture, septic embolic stroke)

— Flank pain or hematuria (renal infarct)

— LUQ pain (splenic infarct/abscess)

— Cold, pulseless limb (peripheral arterial embolus)

Key distinction: Janeway = painless, embolic, palms/soles. Osler = ouch, immune-mediated, finger pads. Step 3 loves this paired contrast.

— Pulmonary edema + acute severe MR/AR → emergent surgical evaluation regardless of antibiotic duration

— Hypotension despite fluids and pressors with large vegetation → consider abscess, fistula, or valve perforation

— Persistent fever >5–7 days on appropriate antibiotics → look for paravalvular extension or metastatic focus

CCS pearl: On a CCS case, document a full cardiac and skin/extremity exam in the febrile bacteremic patient — the simulation rewards finding Janeway lesions or a new murmur that triggers urgent echo and ID consult.

Vital signs first — frame the acuity:

Cardiac exam:

Classic peripheral stigmata (now uncommon, still high-yield):

Embolic exam findings:

Pulmonary findings in right-sided IE: Pleural rub, focal crackles from septic pulmonary emboli; minimal cardiac findings.

Hemodynamic assessment for surgical urgency:

Diagnostic Workup — Initial Labs, Cultures, ECG, Imaging

— Three sets from separate venipuncture sites, drawn at least 1 hour apart when subacute presentation allows (or rapidly back-to-back if septic), before antibiotics

— Aerobic + anaerobic bottles, ≥10 mL each in adults

— In subacute IE, ~95% of untreated cases yield positive cultures within the first three sets

— Hold bottles longer (≥5–7 days, up to 21) if HACEK or fastidious organisms suspected; alert micro lab

— CBC: normocytic anemia of chronic disease, leukocytosis

— ESR, CRP: elevated, useful for trend; not specific

— BMP/LFTs: baseline for nephrotoxic antibiotics

— UA: microscopic hematuria, proteinuria, RBC casts suggest immune-complex glomerulonephritis

— Rheumatoid factor often positive in subacute IE

— Procalcitonin: supportive but not diagnostic

— New PR prolongation, AV block, or bundle branch block in a patient with aortic valve IE strongly suggests perivalvular/aortic root abscess — surgical indication

— Look for ischemic changes from coronary embolization

— Pulmonary edema (left-sided IE with valve destruction)

— Multiple peripheral nodular/cavitary lesions → septic pulmonary emboli (right-sided IE)

— Coxiella burnetii (Q fever), Bartonella, Brucella, Legionella, Mycoplasma

— Beta-D-glucan and Candida PCR if prosthetic valve, immunocompromise, TPN, or indwelling catheter

Step 3 management: A hemodynamically stable subacute IE patient — draw three sets of blood cultures over the first hour, then start empiric therapy; do not wait days. For acute sepsis, draw cultures rapidly and give antibiotics within 1 hour.

Board pearl: Daily ECG on admitted IE patient — a new first-degree AV block is your earliest clue to an aortic root abscess and a surgery trigger.

Blood cultures — the single most important test:

Routine labs:

ECG — order on admission and repeat daily early on:

CXR:

Serologies for culture-negative IE (send early if risk factors):

Diagnostic Workup — Echocardiography and Advanced Imaging

— First-line in all suspected IE — fast, noninvasive, no sedation

— Sensitivity ~60–70% for native valve vegetations, lower (<50%) for prosthetic valves and small lesions

— High specificity (~95%) when expert-read

— Adequate to confirm a clear vegetation in a stable patient with low suspicion ruled out

— Sensitivity >90% for native valve vegetations, ~90% for PVE

— Indications — order TEE if:

— TTE nondiagnostic but clinical suspicion remains high

— Prosthetic valve or intracardiac device

— Suspected perivalvular complications (abscess, fistula, leaflet perforation)

— S. aureus bacteremia with persistent fever or unclear source

— Planning for cardiac surgery

— Repeat TEE in 3–5 days if initial study negative but suspicion persists

— Oscillating intracardiac mass on valve, supporting structures, or implanted material

— Abscess, pseudoaneurysm, or intracardiac fistula

— New partial dehiscence of prosthetic valve

— New valvular regurgitation (worsening or change in pre-existing murmur not sufficient alone)

— Cardiac CT: Excellent for perivalvular abscess, pseudoaneurysm, and pre-op coronary anatomy (avoids cath-related embolization risk)

— ¹⁸F-FDG PET/CT: Useful for prosthetic valve endocarditis ≥3 months post-op and CIED infection — now a Duke major criterion in updated ESC criteria

— Brain MRI: Often reveals silent embolic strokes/microbleeds; influences anticoagulation and surgical timing

— Whole-body CT or PET/CT to map metastatic foci (spleen, vertebrae, joints)

Key distinction: TTE first, TEE if negative with persistent suspicion or if prosthetic valve/device. Don't skip TTE — TEE is not always first-line and has procedural risk.

CCS pearl: In S. aureus bacteremia, TEE is the standard unless TTE clearly shows a vegetation and there are no complications — this is a frequent management vignette.

Transthoracic echocardiogram (TTE):

Transesophageal echocardiogram (TEE):

Key echo findings (a Duke major criterion):

Advanced imaging:

Duke Criteria and Diagnostic Classification

— 1. Blood culture positive for typical IE organism:

— Two separate cultures with viridans strep, S. gallolyticus, HACEK group, S. aureus, or community-acquired enterococci without primary focus

— Persistently positive cultures (≥2 sets >12 hr apart, or all of 3 / majority of ≥4 with first and last >1 hr apart)

— Single positive Coxiella burnetii culture or anti–phase I IgG ≥1:800

— 2. Imaging evidence of endocardial involvement:

— Echo: vegetation, abscess, pseudoaneurysm, intracardiac fistula, valve perforation/aneurysm, new prosthetic dehiscence

— Abnormal ¹⁸F-FDG PET/CT activity on prosthetic valve (≥3 months post-implant) or CIED leads

— Cardiac CT–defined paravalvular lesions

— Predisposition: Predisposing heart condition or IDU

— Fever ≥38.0°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 positivity

— Microbiologic evidence: Positive culture not meeting major criterion, or serologic evidence of active infection consistent with IE

— Definite IE: 2 major OR 1 major + 3 minor OR 5 minor; or pathologic confirmation (histology/culture of vegetation/abscess)

— Possible IE: 1 major + 1 minor OR 3 minor

— Rejected: Firm alternative diagnosis, resolution with ≤4 days of antibiotics, no pathologic evidence at surgery/autopsy, or doesn't meet criteria

Board pearl: Memorize the typical organisms list — testing whether you recognize that two cultures growing viridans strep automatically count as a major criterion is a classic Step 3 angle.

Step 3 management: Score every febrile bacteremic patient against Duke criteria at admission and re-score daily — new echo findings or emboli can upgrade "possible" to "definite" and change therapy duration and surgical decisions.

Modified Duke criteria — the diagnostic backbone for IE. Updated 2023 (Duke-ISCVID) criteria refine microbiology and imaging.

Major criteria:

Minor criteria:

Diagnostic categories:

Empiric and Targeted Antimicrobial Therapy

— Native valve, acute presentation: Vancomycin + ceftriaxone (covers MRSA, streptococci, enterococci, HACEK)

— Add gentamicin only if enterococcal suspicion high and renal function permits

— Prosthetic valve, <1 year post-op: Vancomycin + gentamicin + cefepime + rifampin (covers MRSA, coag-negative staph, gram-negatives, Candida considered separately)

— IDU: Vancomycin (covers MRSA, MSSA, strep); add gram-negative coverage if severe sepsis

— Adjust within 48–72 hr based on culture and susceptibility data

— MSSA, native valve: Nafcillin or cefazolin 6 weeks; cefazolin preferred if no CNS involvement (better tolerance)

— MRSA, native valve: Vancomycin 6 weeks; daptomycin alternative (high dose ≥8–10 mg/kg)

— MSSA/MRSA, prosthetic valve: Beta-lactam (or vanco) + rifampin × 6 wk + gentamicin × first 2 weeks

— Viridans strep, penicillin-susceptible (MIC ≤0.12): Penicillin G or ceftriaxone × 4 weeks (2 wk with gentamicin if uncomplicated native valve)

— Enterococcus faecalis: Ampicillin + ceftriaxone × 6 weeks (preferred over amp+gent in renal impairment or HLAR)

— HACEK: Ceftriaxone × 4 weeks (6 wk if prosthetic)

— Culture-negative, native: Ampicillin-sulbactam + gentamicin, or vanco + cefepime + doxycycline depending on epidemiology

— Coxiella (Q fever): Doxycycline + hydroxychloroquine ≥18 months (native), longer for prosthetic

Key distinction: Cefazolin > nafcillin for MSSA in most cases (less hepatotoxicity, less hypokalemia); nafcillin preferred in CNS infection due to better CSF penetration.

Step 3 management: Outpatient parenteral antibiotic therapy (OPAT) is appropriate after ≥2 weeks of inpatient stability in selected uncomplicated cases — coordinate weekly labs (CBC, BMP, drug levels), PICC line care, and ID follow-up. Document teach-back on line precautions before discharge.

Empiric therapy — start AFTER three blood culture sets, unless septic:

Targeted regimens (standard durations 4–6 weeks IV from first negative culture):

Surgical Management and Source Control

— Heart failure from valve dysfunction (acute severe AR/MR with pulmonary edema) — emergent

— Uncontrolled infection: persistent bacteremia >5–7 days on appropriate therapy, perivalvular abscess, fistula, pseudoaneurysm, heart block

— Fungal IE or highly resistant organisms (e.g., MDR gram-negatives)

— Prosthetic valve dehiscence or worsening prosthetic dysfunction

— Recurrent emboli despite appropriate antibiotics, or large vegetation >10 mm after one embolic event

— Large mobile vegetation >10 mm even without prior emboli, especially anterior mitral leaflet

— Recurrent emboli on appropriate therapy

— Non-hemorrhagic, small embolic stroke: surgery not delayed if otherwise indicated

— Major ischemic stroke or intracranial hemorrhage: delay 3–4 weeks if feasible

— Get brain MRI + CTA/MRA to screen for mycotic aneurysms before cardiopulmonary bypass and anticoagulation

— Remove infected CIEDs entirely (generator + leads) for any device-related IE

— Drain splenic abscesses (percutaneous or splenectomy)

— Treat dental foci before or shortly after valve surgery to prevent recurrence

— Remove indwelling catheters/lines that may be the seed source

— Mortality 5–15% for valve replacement in IE; higher with abscess, multivalve disease, or salvage

— Choice of mechanical vs bioprosthetic valve depends on age, anticoagulation candidacy, and patient preference — shared decision-making is a Step 3 expectation

CCS pearl: Order cardiothoracic surgery consult early in any IE with HF, abscess, fungal pathogen, or large vegetation. Delay in surgical consult is a common CCS penalty.

Board pearl: New AV block + aortic valve IE = aortic root abscess = operate. Don't keep escalating antibiotics.

Class I indications for surgery (don't wait through full antibiotic course):

Class IIa — consider early surgery (within first week):

Timing after stroke:

Source control beyond valve surgery:

Surgical risk discussion:

Special Populations — Elderly and Renal/Hepatic Impairment

— More likely to have degenerative valve disease, prior valve replacement, healthcare exposure

— Atypical presentation: absent fever, delirium, failure to thrive, weight loss, anemia — IE may masquerade as malignancy

— Enterococcus and S. gallolyticus IE more common; if S. gallolyticus → colonoscopy for occult colorectal neoplasia

— Higher surgical mortality; weigh frailty, cognitive status, and goals of care

— Polypharmacy → carefully review for drug interactions (warfarin + rifampin or doxycycline; QT prolongation with daptomycin + other agents)

— Hemodialysis with tunneled catheters is a major IE risk factor; S. aureus dominates

— Vancomycin dosed by trough or AUC monitoring (target AUC₂₄ 400–600); dose post-HD

— Avoid aminoglycosides if possible (nephrotoxicity, ototoxicity); when used, monitor levels and renal function every 2–3 days

— Daptomycin requires dose adjustment in CrCl <30 (give q48h); monitor CK weekly — risk of rhabdomyolysis

— Remove infected dialysis catheter and arrange alternative access (temporary line at different site) before continuing therapy

— Avoid hepatotoxic agents when possible: nafcillin (cholestasis), high-dose oxacillin, ceftriaxone in cirrhosis (biliary sludging)

— Cefazolin preferred over nafcillin in liver disease

— Rifampin: induces CYP3A4, hepatotoxic — check LFTs at baseline and weekly; expect orange-red discoloration of secretions (counsel patient)

Key distinction: In elderly IE, think S. gallolyticus and Enterococcus; in young IDU, think S. aureus; in dialysis patients, think S. aureus from line.

Step 3 management: Hemodialysis patient with S. aureus bacteremia — TEE for IE, remove and culture catheter tip, place temporary line at a different site, and plan ≥4–6 weeks of IV therapy with dialysis-friendly dosing of vancomycin or cefazolin.

Board pearl: S. gallolyticus IE in any adult → colonoscopy is the next best step regardless of age.

Elderly (>65, rising IE incidence):

Chronic kidney disease and dialysis patients:

Hepatic impairment:

Special Populations — Pregnancy, Pediatrics, and IDU

— Rare but high-risk; maternal mortality up to 20–30%, fetal loss substantial

— Physiologic murmurs and tachycardia obscure exam; low threshold for echo with persistent fever

— Safe antibiotics: penicillins, cephalosporins, vancomycin (Category B/no human evidence of harm)

— Avoid: aminoglycosides (fetal ototoxicity — use only if life-threatening), tetracyclines (teeth/bone), fluoroquinolones (relative), rifampin (use cautiously, may increase bleeding risk near delivery), TMP-SMX in first/third trimesters

— Surgery on cardiopulmonary bypass during pregnancy carries 15–35% fetal loss; delivery before maternal surgery preferred if fetus viable

— Multidisciplinary team: cardiology, ID, MFM, cardiac surgery, anesthesiology

— Most cases in children with congenital heart disease (especially unrepaired VSDs, tetralogy of Fallot, palliated single-ventricle physiology)

— Neonatal IE associated with central catheters, prematurity; S. aureus and coag-negative staph dominate

— Vegetations may be on prosthetic conduits or shunts

— Same Duke criteria apply with pediatric weight-based dosing

— Right-sided IE (tricuspid) most common, but left-sided increasingly seen

— S. aureus (often MRSA) is dominant; add coverage for Pseudomonas if "pasilla" or unusual drug preparations, also consider polymicrobial and fungal

— Pair antibiotics with addiction treatment — buprenorphine or methadone initiation in hospital improves IE outcomes and reduces relapse

— Harm reduction: naloxone prescription, syringe service referral, hepatitis C/HIV screening, vaccinations

— OPAT historically controversial — newer evidence supports it in selected patients with stable recovery and adequate housing/social supports

Step 3 management: IDU patient with IE — initiate medication for opioid use disorder during admission; this is now standard of care and tested as a longitudinal management decision.

Board pearl: Pregnant patient with IE — vancomycin + ceftriaxone is safe empiric therapy; avoid aminoglycosides unless absolutely necessary.

Pregnancy:

Pediatric IE:

Injection drug use (IDU) — Step 3 high-yield:

Complications and Adverse Outcomes

— Acute valvular regurgitation → heart failure (most common cause of death in IE)

— Perivalvular abscess → conduction block, fistula, pseudoaneurysm

— Pericarditis, myocardial abscess, purulent pericarditis (especially S. aureus)

— Coronary embolization → acute MI

— Cardiac tamponade from ruptured pseudoaneurysm

— Stroke is the most feared — embolic infarcts, mycotic aneurysm rupture → intracerebral hemorrhage

— Splenic infarcts/abscesses → persistent fever despite therapy; splenectomy may be needed before valve surgery if anticoagulation planned

— Renal infarcts, mesenteric ischemia, acute limb ischemia

— Septic pulmonary emboli (right-sided IE) → cavitary nodules, empyema, pneumothorax

— Vertebral osteomyelitis/discitis — back pain in S. aureus bacteremia → MRI spine

— Psoas abscess, septic arthritis, epidural abscess

— Glomerulonephritis (immune-complex deposition) — hematuria, AKI, RBC casts; treat the IE, supportive renal care

— Vasculitis, arthralgias

— Vancomycin: AKI, infusion reactions (DRESS, "red man")

— Aminoglycosides: nephro- and ototoxicity

— Daptomycin: rhabdomyolysis, eosinophilic pneumonia

— Linezolid: thrombocytopenia, peripheral neuropathy, serotonin syndrome

— Line complications: DVT, catheter-related bloodstream infection (a new bacteremia in a treated patient suggests this)

Key distinction: Persistent fever >5–7 days on appropriate therapy = look for abscess (perivalvular, splenic, vertebral), drug fever, recurrent emboli, or drug-resistant organism — not "just keep waiting."

Step 3 management: New focal neuro deficit in IE → non-contrast head CT first, then MRI brain ± CTA/MRA for mycotic aneurysm; defer surgery 3–4 weeks if hemorrhage, sooner if ischemic and small.

Cardiac complications:

Embolic complications (20–50%):

Metastatic infections:

Immune-mediated complications:

Drug-related complications during prolonged IV therapy:

When to Escalate Care — ICU, Consults, and Triage

— Hemodynamic instability (septic shock, cardiogenic shock from acute regurgitation)

— Acute pulmonary edema from valvular destruction

— Severe neurologic compromise (large stroke, intracranial hemorrhage, status epilepticus from emboli)

— Need for vasopressors, mechanical ventilation, or temporary mechanical circulatory support

— Post-operative recovery from valve surgery

— Infectious Diseases: Antibiotic selection, OPAT planning, duration, source-control strategy — improves mortality

— Cardiology: Echo interpretation, hemodynamic management, valve assessment

— Cardiothoracic Surgery: Any Class I surgical indication, large vegetation, prosthetic valve IE, or CIED-related IE

— Neurology/Neurosurgery: If embolic stroke or mycotic aneurysm

— Addiction medicine / Social work: All IDU-related IE

— Dental consultation when oral source suspected before valve surgery

— All IE patients require inpatient initiation of IV antibiotics with daily monitoring

— Minimum 2 weeks inpatient before considering OPAT for stable, uncomplicated cases (longer for S. aureus and prosthetic valves)

— Repeat blood cultures every 48–72 hours until clear, then again with any new fever

— A multidisciplinary team approach (cardiology, ID, surgery, imaging) is recommended by AHA/ACC and ESC; reduces mortality by 25–50% in studies

— Particularly important for surgical timing decisions

CCS pearl: On a CCS case, ordering "ID consult," "cardiology consult," and "cardiothoracic surgery consult" early — even before the abscess is identified — demonstrates appropriate Step 3 decision-making and avoids hidden penalties for delayed escalation.

Step 3 management: Persistent S. aureus bacteremia at 72 hours despite vancomycin → check TEE (if not done), drug level/MIC, infected hardware, metastatic foci; consider switching to daptomycin or combination therapy in consultation with ID.

ICU admission criteria:

Mandatory consultations — order early on CCS:

Inpatient vs outpatient decisions:

Endocarditis Team ("Heart Team"):

Key Differentials — Other Cardiac and Endovascular Mimics

— Sterile fibrin-platelet vegetations on valves

— Associated with advanced malignancy (especially adenocarcinomas — pancreatic, gastric, lung), DIC, chronic illness

— Presents with systemic emboli but no fever, negative blood cultures, normal CRP/ESR pattern

— Treat the underlying malignancy + anticoagulation (heparin/LMWH) — opposite approach from IE

— Sterile vegetations on either side of the mitral valve (classically)

— Associated with SLE and antiphospholipid syndrome

— Treat the underlying autoimmune disease; anticoagulate if APS or embolic events

— Post-streptococcal, immune-mediated

— Jones criteria (carditis, polyarthritis, chorea, erythema marginatum, subcutaneous nodules + minor criteria + evidence of preceding GAS infection)

— Can mimic acute IE with new murmur and fever after pharyngitis

— Mimics IE with embolic strokes, constitutional symptoms, elevated inflammatory markers

— Tumor "plop" auscultatory finding; echo shows pedunculated mass usually attached to interatrial septum

— Treat with surgical excision; no antibiotics

— Small, mobile valvular tumor mimicking vegetation on echo

— Cultures negative, no systemic infection signs; can still embolize

— Bacteremia from endovascular infection without true valvular involvement; CT/PET helpful

Key distinction: Fever + emboli + positive cultures = IE. No fever + emboli + cancer/SLE/APS = NBTE or Libman-Sacks — don't reflexively give antibiotics.

Board pearl: Embolic stroke in a patient with metastatic pancreatic cancer and no fever — NBTE; anticoagulate, treat cancer, do not give antibiotics.

Marantic (nonbacterial thrombotic) endocarditis (NBTE):

Libman-Sacks endocarditis:

Rheumatic carditis:

Acute rheumatic fever vs IE: Joint pain pattern (migratory polyarthritis), recent strep throat, ASO titer rise vs persistent bacteremia and echo vegetation

Cardiac myxoma (atrial myxoma):

Papillary fibroelastoma:

Infected aortic graft or pseudoaneurysm:

Key Differentials — Systemic Mimics of IE

— ANCA-associated vasculitis (GPA, MPA): Fever, pulmonary nodules/cavities, glomerulonephritis, low-grade emboli-like phenomena — can mimic right-sided IE with septic pulmonary emboli

— Check ANCA, anti-PR3, anti-MPO; cultures negative

— Polyarteritis nodosa: fever, mononeuritis multiplex, abdominal pain; angiography shows microaneurysms

— Stroke + valvular disease may be mistaken for embolic IE; cultures negative, no fever

— AV block in endemic area with tick exposure, erythema migrans history — not a vegetation; treat with doxycycline or ceftriaxone

— FUO mimicking subacute IE; appropriate epidemiology and specific cultures/serologies needed

— Night sweats, weight loss, low-grade fever, splenomegaly mimic subacute IE

— Imaging and biopsy distinguish; cultures negative

— Especially in a patient already on antibiotics for another reason; eosinophilia, rash, transaminitis

— Bacteremia from a line tip with no valvular involvement; echo negative — distinction matters because shorter therapy possible

— S. aureus CRBSI mandates TEE because of high IE rate (~25%)

— Histoplasmosis with mediastinitis, Strongyloides hyperinfection in steroid users

Key distinction: Persistent bacteremia + vegetation = IE. Transient bacteremia + line + negative echo = CRBSI — different durations (14 days vs 4–6 weeks), different surgical implications.

Step 3 management: Catheter-related S. aureus bacteremia — remove line, TEE within 5–7 days (even if asymptomatic), treat ≥14 days if no IE, ≥4 weeks if IE confirmed; repeat blood cultures at 48–72 hours to confirm clearance.

Vasculitides:

Atrial fibrillation with cardioembolic stroke:

Lyme carditis:

Tuberculosis and brucellosis:

Lymphoma and other malignancy:

Drug fever / drug reaction (DRESS):

Catheter-related bloodstream infection without endocarditis:

Endemic mycoses and parasitic infections (rare in US but tested):

Secondary Prevention, Discharge Planning, and Prophylaxis

— High-risk cardiac conditions only:

— Prosthetic valves (including TAVR) or prosthetic material used in valve repair

— Previous IE

— Unrepaired cyanotic congenital heart disease, including palliative shunts/conduits

— Repaired CHD with residual defects at/adjacent to prosthetic material

— Cardiac transplant recipients with valvulopathy

— Procedures requiring prophylaxis:

— Dental procedures involving manipulation of gingival tissue, periapical region, or perforation of oral mucosa

— Invasive respiratory procedures with mucosal incision/biopsy

— Procedures on infected skin/musculoskeletal tissue

— NOT recommended for routine GI/GU procedures in absence of active infection

— Regimen: Amoxicillin 2 g PO 30–60 min before procedure (cephalexin or azithromycin if PCN-allergic; clindamycin no longer first-line due to C. difficile risk)

— Definitive antibiotic plan with end date documented

— PICC line care education, signs of line infection (fever, redness, discharge)

— Weekly labs: CBC with diff, BMP, LFTs, drug levels (vanco trough or AUC), CRP trend

— Repeat blood cultures if any new fever

— Follow-up TTE at end of therapy as new baseline for the valve

— Dental evaluation before discharge or within first weeks to eliminate oral foci; comprehensive cleanup before any future valve surgery

— Vaccination review (pneumococcal, influenza, COVID, hepatitis B in dialysis)

— For IDU: MOUD continuation plan, naloxone, harm reduction kit, addiction follow-up scheduled before discharge

— Yearly cardiology follow-up with TTE for residual valve dysfunction

— Maintain meticulous oral hygiene — most effective long-term prevention

Board pearl: Mitral valve prolapse alone is NOT an indication for endocarditis prophylaxis — a frequently tested Step 3 point reflecting the 2007 AHA guideline change.

Step 3 management: At discharge, every IE patient should leave with documented dental follow-up, valve surveillance plan, and prophylaxis card for future procedures.

Endocarditis prophylaxis (AHA/ACC, narrow indications):

Discharge planning checklist:

Long-term valve surveillance:

Follow-Up, Monitoring, and Counseling

— Daily vitals, exam (new murmur, HF signs), and ECG initially

— Blood cultures every 48–72 hours until two consecutive negatives

— Inflammatory markers (CRP) weekly to track resolution

— Repeat TTE at 1 week and at end of therapy; TEE if new symptoms or complications

— Drug-specific labs:

— Vancomycin: trough (15–20 mg/L) or AUC₂₄ 400–600 every 3–5 days, CBC, BMP twice weekly

— Aminoglycosides: peak/trough levels, weekly audiogram if prolonged

— Daptomycin: CK weekly

— Linezolid: CBC weekly (platelets)

— Rifampin: LFTs weekly, counsel on orange secretions, contraceptive failure, and drug interactions

— ID clinic within 1 week of discharge if on OPAT; weekly during therapy

— Cardiology within 2–4 weeks after completion with end-of-treatment echo

— Primary care follow-up for chronic disease management within 2 weeks

— Long-term: annual cardiology + echo; lifetime increased IE risk

— Patient must know: signs of recurrent IE (fever, night sweats, weight loss), how to access blood cultures before taking antibiotics elsewhere

— Dental hygiene education and consistent dental visits every 6 months

— Carry a prophylaxis information card listing valve status and recommended pre-procedure regimen

— Avoid body piercings and tattoos in unregulated settings

— IDU patients: continued MOUD, harm reduction, and regular ID follow-up

CCS pearl: Schedule the follow-up TTE at end of therapy during the discharge order set — it's a frequently tested Step 3 longitudinal management item.

Step 3 management: Any IE patient calling with fever after completing therapy — draw 3 sets of blood cultures BEFORE starting empiric antibiotics and arrange echo; never reflexively prescribe oral antibiotics over the phone.

In-hospital monitoring cadence:

Post-discharge follow-up:

Counseling priorities:

Cardiac rehab: Generally not formally indicated for IE alone, but post-surgical valve patients qualify and benefit; address deconditioning from prolonged hospitalization.

Ethical, Legal, and Patient Safety Considerations

— Patients with recurrent IE from continued injection drug use raise difficult questions about repeat valve surgery

— Standard of care: Do not withhold life-saving surgery based on substance use alone. Active addiction is a treatable disease; decisions should follow patient capacity, prognosis, and goals of care — not stigma.

— Engage ethics consult, palliative care, and addiction medicine early; require coupling of surgery with comprehensive MOUD and harm-reduction commitments

— Patients with septic encephalopathy or stroke may lack decision-making capacity for valve surgery

— Use surrogate decision-makers per state hierarchy (spouse, adult child, parent, sibling); confirm advance directives and POLST

— Document capacity assessment, risks/benefits/alternatives, and surrogate decisions clearly

— Suspected illicit drug use is not mandatorily reportable (confidentiality protects engagement); however, child neglect in a parent with IE from IDU may trigger reporting depending on state law

— Report cases of suspected abuse, HIV/hepatitis C per state public health rules (often required), and certain reportable infections

— Long IV therapy at OPAT facilities creates handoff risk: medication errors, line infections, missed labs

— Ensure medication reconciliation at every transition (admission → floor → OPAT → discharge)

— Use structured handoff tools (e.g., I-PASS) and confirm receiving provider has the antibiotic end date, lab schedule, and follow-up plan

— IV therapy at home vs SNF vs infusion center has insurance and access implications; involve case management early

— Persistent fever or unresolved symptoms should prompt diagnostic reassessment, not just antibiotic escalation — avoid "anchoring" bias

— Encourage incident reporting on adverse drug events (vancomycin AKI, line infections) to improve system safety

Board pearl: Refusing valve surgery solely because a patient has substance use disorder is ethically inappropriate and inconsistent with current cardiothoracic surgery society guidance; the right answer integrates surgery with addiction treatment.

Repeat IE in active IDU — the "second valve" dilemma:

Informed consent in critical illness:

Mandatory and ethical reporting:

Transition-of-care risks (Step 3 favorite):

OPAT and IDU: Historically restricted, but evidence supports OPAT in select stable patients on MOUD with reliable housing — refusal must be individualized, not categorical, to avoid disparate treatment

Cost and access:

Patient safety culture:

High-Yield Associations and Rapid-Fire Clinical Facts

— Viridans strep + dental work → subacute IE on previously abnormal valve

— S. aureus → acute IE, native valve destruction, IDU (tricuspid), prosthetic valves, dialysis catheters

— Coag-negative staph (S. epidermidis) → early prosthetic valve endocarditis

— S. gallolyticus (bovis) → colon cancer; mandates colonoscopy

— Enterococcus → elderly men post-GU instrumentation, women post-OB/GYN procedures

— HACEK (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella) → culture-negative or slow-growing; oral flora

— Coxiella burnetii → Q fever IE; livestock, parturient animals; diagnosed by serology

— Bartonella henselae/quintana → cat exposure, homelessness/body lice; culture-negative

— Candida → IVDU, TPN, prolonged catheters; large vegetations, embolic risk; surgery + echinocandin then azole

— Left-sided (mitral > aortic): most native valve IE

— Tricuspid: IDU, indwelling catheters, pacemaker leads

— Pulmonic: rare; congenital heart disease

— Roth spots, Janeway lesions, Osler nodes, splinter hemorrhages = peripheral stigmata

— Microscopic hematuria + RBC casts in IE = immune-complex GN

— Splenomegaly + anemia + fever = chronic subacute IE

— New AV block + aortic valve IE = perivalvular abscess

— Septic pulmonary emboli (peripheral nodular/cavitary) = right-sided IE

— Cefazolin > nafcillin for non-CNS MSSA (less hepatotoxicity)

— Rifampin is "anti-biofilm" — used for prosthetic valve staph IE

— Daptomycin inactivated by surfactant → useless for pulmonary infection (won't help septic pulmonary emboli treated as pneumonia)

— Heart failure

— Emboli (recurrent, or large vegetation >10 mm)

— Abscess (perivalvular, conduction block)

— Resistant or fungal organism

— Transcatheter/prosthetic dehiscence

Board pearl: Daptomycin lung penetration is poor and surfactant inactivates it — never use daptomycin for pneumonia, including septic pulmonary emboli as primary pathology.

Organism-disease associations (Step 3 staples):

Valve preferences:

Classic associations:

Pharmacology pearls:

Surgical triggers mnemonic — "HEART":

Board Question Stem Patterns

— 55-year-old with poor dentition, low-grade fevers × 6 weeks, weight loss, new MR murmur, splenomegaly.

— Next step: 3 sets of blood cultures from separate sites + TTE; expect viridans strep; treat with penicillin G or ceftriaxone 4 weeks.

— 28-year-old, IV heroin user, fever and pleuritic chest pain, CXR with multiple peripheral nodular lesions.

— Next step: Blood cultures × 3, vancomycin empirically, TTE/TEE; start MOUD before discharge.

— 70-year-old with bioprosthetic AVR 8 months ago, fever, new first-degree AV block.

— Diagnosis: Early PVE with aortic root abscess; surgical consult urgently; empiric vanco + gentamicin + cefepime + rifampin.

— Elderly patient with viridans-like strep IE on echo; subspecies gallolyticus.

— Next step after IE treatment: Colonoscopy for colorectal neoplasia.

— Cat owner, homeless patient, or farmer with prolonged febrile illness, vegetation on echo, negative cultures × 5.

— Next step: Serologies for Bartonella, Coxiella burnetii, Brucella; treat empirically per epidemiology.

— 32-year-old IVDU with hemiparesis, fever, S3, MRI shows multiple embolic infarcts.

— Diagnosis: IE with septic emboli; if no hemorrhage and small infarct, surgery is not delayed when indicated.

— Patient with pancreatic adenocarcinoma, embolic strokes, no fever, negative cultures, valve vegetations.

— Diagnosis: NBTE; anticoagulate, treat malignancy, no antibiotics.

— Patient with mitral valve prolapse asks about prophylaxis before dental cleaning.

— Answer: No prophylaxis indicated (MVP not on the high-risk list).

— S. aureus IE, still bacteremic despite vancomycin.

— Next step: TEE (if not done), assess vanco MIC/trough, search for metastatic foci (vertebral MRI, abdominal imaging), surgical consult.

Step 3 management: The recurring testable thread — cultures before antibiotics, TTE then TEE, Duke criteria scoring, early ID and CT surgery consult, treat the underlying source (line, dental, drug use).

Stem 1 — Classic subacute IE:

Stem 2 — IDU with right-sided IE:

Stem 3 — Prosthetic valve + new AV block:

Stem 4 — S. gallolyticus bacteremia:

Stem 5 — Culture-negative IE:

Stem 6 — Embolic stroke in young patient:

Stem 7 — Marantic vs infective:

Stem 8 — Prophylaxis question:

Stem 9 — Persistent bacteremia at day 5:

One-Line Recap

Infective endocarditis is diagnosed by applying the modified Duke criteria to clinical, microbiologic (≥3 blood culture sets), and echocardiographic data (TTE first, then TEE), treated with prolonged organism-targeted IV antibiotics and early multidisciplinary surgical evaluation for heart failure, abscess, persistent infection, large vegetations, fungal pathogens, or prosthetic involvement.

— Duke major criteria: Two positive cultures with typical IE organism (viridans strep, S. gallolyticus, HACEK, S. aureus, community-acquired enterococci) OR persistent bacteremia OR single Coxiella serology + echo evidence (vegetation, abscess, new dehiscence, new regurgitation).

— Definite IE: 2 major, OR 1 major + 3 minor, OR 5 minor, OR pathologic confirmation.

— Empiric therapy: Native valve → vanco + ceftriaxone; prosthetic valve <1 yr → vanco + gentamicin + cefepime + rifampin; tailor in 48–72 hr.

— Surgical "HEART" triggers: Heart failure, Emboli (recurrent or >10 mm), Abscess/heart block, Resistant/fungal organism, Transcatheter/prosthetic dehiscence.

— Mandatory follow-up moves: S. gallolyticus → colonoscopy; IDU IE → start MOUD before discharge; all IE → end-of-therapy TTE and lifelong dental hygiene.

— Prophylaxis is narrow: Prosthetic valves, prior IE, unrepaired cyanotic CHD, repaired CHD with residual defects at prosthetic material, cardiac transplants with valvulopathy — for dental, respiratory mucosal, or infected skin procedures. MVP does NOT qualify.

— Don't forget the consult triad: ID, cardiology, cardiothoracic surgery — early and together as an Endocarditis Team.

Board pearl: When a Step 3 vignette gives you fever + new murmur or S. aureus bacteremia, the answer pathway is always cultures → empiric vanco-based regimen → TTE/TEE → Duke scoring → ID and surgery consult; deviations from this sequence usually mark the wrong choice.

High-yield recap bullets: