Infective endocarditis (IE) is an infection of the cardiac endothelium — most commonly involving heart valves — with in-hospital mortality of approximately 15–30%. It presents acutely (high fever, sepsis, rapid valve destruction) or subacutely (weeks of malaise, low-grade fevers, weight loss). [1-3] Diagnosis relies on the 2023 Duke-ISCVID Criteria, integrating clinical, microbiologic, and imaging findings. [2][4]
The following figure illustrates the pathogenesis from initial bacteremia through vegetation formation and embolic complications:
1. History
- Onset and tempo: Acute (hours–days) vs. subacute (weeks–months); sudden high fever with rigors suggests S. aureus, while insidious fatigue/malaise suggests viridans streptococci or coagulase-negative staphylococci [1][3]
- Symptom characterization: Fever (present in ~78% of cases), chills, night sweats, dyspnea, back pain, arthralgias, weight loss [1-2]
- Embolic symptoms: New focal neurologic deficits (stroke), pleuritic chest pain (septic pulmonary emboli), flank pain (splenic/renal infarct), abdominal pain [6]
- Cardiac symptoms: Progressive dyspnea, orthopnea, lower extremity edema (heart failure from acute valvular regurgitation) [2]
- Important negatives: Absence of fever does not exclude IE, especially in elderly, immunocompromised, or subacute presentations [6]
- Key questions: Recent dental procedures? IV drug use? Recent hospitalization or intravascular catheter? Prior valve surgery or prosthetic valve? History of IE? Recent skin/soft tissue infection?
2. Alarm Features
- Acute heart failure — new dyspnea, pulmonary edema, cardiogenic shock from acute severe valvular regurgitation [7-8]
- Persistent bacteremia (>5–7 days on appropriate antibiotics) — suggests uncontrolled infection, abscess, or need for surgery [7]
- Neurologic events — stroke, intracranial hemorrhage, mycotic aneurysm rupture, brain abscess [6][9]
- Septic shock (occurs in ~7% of cases) [2]
- New conduction abnormalities (heart block) — suggests perivalvular abscess, especially with aortic valve IE [7-8]
- Large vegetations >10 mm with embolic events — high risk for recurrent embolization [7]
- Paravalvular abscess, fistula, or prosthetic valve dehiscence [8-9]
3. Medications
Empiric therapy (before culture results)
- Native valve: Vancomycin + ceftriaxone [1][6][10]
- Prosthetic valve: Vancomycin + cefepime or piperacillin-tazobactam [6][10]
- If oral/GI source suspected: ampicillin-sulbactam may replace ceftriaxone [6]
- If Pseudomonas risk: cefepime or piperacillin-tazobactam [6]
Definitive therapy (organism-directed)
- MSSA: Nafcillin/oxacillin or cefazolin (4–6 weeks); beta-lactams preferred over vancomycin for higher cure rates [1][6][11]
- MRSA: Vancomycin (30 mg/kg/day divided q8–12h) or daptomycin (6 weeks) [6][11]
- Viridans streptococci: Ceftriaxone 2g IV daily or penicillin G (4 weeks) [6][11]
- Enterococcus: Ampicillin + ceftriaxone (preferred) or ampicillin + gentamicin (≥6 weeks regardless of valve type); avoid gentamicin in elderly/CKD patients [1][6]
Oral step-down: The POET trial supports transition to oral antibiotics in the continuation phase for stable patients with left-sided IE who no longer require surgery [2][10]
Cautions
- Aminoglycosides: nephrotoxicity/ototoxicity — limit duration to ≤2 weeks; avoid in elderly/renal impairment [6]
- Rifampin: reserve for prosthetic valve IE; do not use as monotherapy [1][10]
- Avoid empiric antibiotics before blood cultures are drawn whenever possible [1][8]
4. Diet
- No specific dietary triggers or restrictions for IE itself
- Adequate nutrition is critical during prolonged hospitalization; consider nutritional support for cachectic patients
- Ensure adequate hydration, particularly with nephrotoxic antibiotics (vancomycin, aminoglycosides)
- Patients with heart failure from IE should follow sodium and fluid restriction as appropriate
5. Review of Systems
- Constitutional: Fever, chills, rigors, night sweats, weight loss, fatigue, malaise [1][6]
- Cardiovascular: Dyspnea, orthopnea, PND, palpitations, chest pain, syncope [2]
- Neurologic: Headache, focal weakness, vision changes, confusion, seizures [6]
- Musculoskeletal: Back pain, arthralgias (may suggest spondylodiscitis or septic arthritis) [1]
- Skin: New rash, painful fingertip lesions, painless palmar/plantar lesions [1][6]
- Renal: Hematuria, decreased urine output (glomerulonephritis, renal infarct) [9]
- Pulmonary: Cough, pleuritic chest pain, hemoptysis (right-sided IE with septic pulmonary emboli) [12]
- Abdominal: Left upper quadrant pain (splenic infarct/abscess) [6]
6. Collateral History and Family History
- Collateral: IV drug use history (type of drug, injection practices, water source), recent dental work, recent hospitalization or procedures, indwelling catheters, prior antibiotic use [3][11]
- Social context: Homelessness (risk for Bartonella quintana), farm animal exposure (risk for Coxiella burnetii/Q fever) [1]
- Family history: Generally not a major contributor; however, congenital heart disease (e.g., bicuspid aortic valve) may be familial and is a predisposing condition [2-3]
- Prior cardiac history: Previous IE (strong risk factor for recurrence), known valvular disease, prior valve surgery [2][9]
7. Risk Factors
Cardiac
- Prior IE, prosthetic heart valve, prior valve repair [2][9]
- Valvular heart disease (degenerative, rheumatic, congenital — especially bicuspid aortic valve) [1][3]
- Cardiac implantable electronic devices (CIEDs), ventricular assist devices [2]
- Hypertrophic obstructive cardiomyopathy [9]
Non-cardiac
- IV drug use — most common risk factor in younger patients; predominantly right-sided (tricuspid) IE [11-12]
- Age >60 years, male sex [2-3]
- Hemodialysis, central venous catheters, indwelling intravascular devices [1][3]
- Poor dentition, recent dental procedures [1-2]
- Immunosuppression, diabetes, chronic liver disease, neoplastic disease [1][3]
- Recent hospitalization (nosocomial IE accounts for up to one-third of US cases) [6]
8. Differential Diagnosis
- Bacteremia without endocarditis — most common mimic; distinguish by echocardiographic findings and persistence of bacteremia [1][12]
- Nonbacterial thrombotic endocarditis (marantic endocarditis) — sterile vegetations in malignancy or hypercoagulable states; culture-negative [3]
- Libman-Sacks endocarditis — associated with SLE/antiphospholipid syndrome; sterile vegetations [3]
- Atrial myxoma — intracardiac mass mimicking vegetation on echo; can cause embolic phenomena and constitutional symptoms
- Rheumatic fever — fever, murmur, arthralgias; distinguished by Jones criteria, negative blood cultures
- Systemic vasculitis (e.g., ANCA-associated) — can mimic immunologic phenomena of IE
- Occult malignancy — fever of unknown origin, weight loss, elevated inflammatory markers
- Other causes of FUO — lymphoma, connective tissue disease, deep-seated abscess
9. Past Medical History
- Prior IE — strongest predictor of recurrence [2][9]
- Prosthetic valve or valve repair — prosthetic valve IE has distinct microbiology (early: coagulase-negative staphylococci; late: similar to native valve) [4][6]
- Congenital heart disease — especially unrepaired or palliated lesions [9]
- Rheumatic heart disease — most common predisposing condition in developing countries [1]
- Chronic kidney disease/hemodialysis — increased risk and impacts antibiotic selection [1][3]
- Diabetes, chronic liver disease, immunosuppression [1]
- History of IV drug use — even remote history is relevant [11]
10. Physical Exam
Vital signs
Cardiac
- New murmur (48%) or worsening of known murmur (20%) — most common sign [6]
- New aortic regurgitation murmur is particularly concerning
- Signs of heart failure: JVD, pulmonary crackles, peripheral edema [2]
Skin/extremities
- Janeway lesions — painless erythematous macules/papules on palms and soles (~3.5%) [2][6]
- Osler nodes — painful, tender nodules on fingers/toes (~2%) [2][6]
- Splinter hemorrhages — linear subungual hyperpigmentation [6]
- Petechiae — conjunctival, oral mucosa, skin [1]
Eyes
- Roth spots — hemorrhagic retinal lesions with pale centers (~1.4%); perform fundoscopy [2]
- Conjunctival hemorrhages [1]
Abdominal
- Splenomegaly (more common in subacute IE) [2]
- LUQ tenderness (splenic infarct/abscess)
Neurologic
Musculoskeletal
11. Lab Studies
Essential
- Blood cultures — at least 2–3 sets from separate venipuncture sites before antibiotics; first and last drawn ≥1 hour apart [1][8][12]
- CBC with differential (leukocytosis, anemia of chronic disease)
- CRP, ESR (elevated in >90%)
- BMP/CMP (renal function for antibiotic dosing, electrolytes)
- Urinalysis (hematuria from glomerulonephritis or renal infarct)
- Procalcitonin (may help distinguish IE from non-infectious causes)
If culture-negative
- Serologies: Coxiella burnetii phase I IgG (>1:800 is a major Duke criterion), Bartonella IgG/IgM [1][4][6]
- PCR: Bartonella, C. burnetii, Tropheryma whipplei [2][4][6]
- Amplicon/metagenomic sequencing if available [2][4]
Monitoring
- Repeat blood cultures q48h until clearance documented [1]
- Vancomycin trough levels (target AUC/MIC-based dosing)
- Renal function (especially with vancomycin, aminoglycosides) [6]
- Rheumatoid factor, complement levels (immunologic phenomena) [9]
12. Imaging
First-line
- Transthoracic echocardiography (TTE)[6][11]
Second-line / when TTE is negative or equivocal
- Transesophageal echocardiography (TEE) — sensitivity ~90–96% for both native and prosthetic valves; recommended for all prosthetic valves, possible IE by Duke criteria, or suspected complicated IE [6][11]
- If TEE is negative but suspicion remains high, repeat in 5–7 days [1]
Advanced imaging (2023 Duke-ISCVID criteria now include these):
- 18F-FDG PET/CT — particularly useful for prosthetic valve IE, CIEDs, and detecting metastatic infection (splenic abscess, spondylodiscitis); may be more sensitive than TEE for prosthetic valves [2][4][6]
- Cardiac CT — identifies abscess, pseudoaneurysm, fistula; useful for surgical planning; less sensitive for small (<4 mm) vegetations [6]
- Brain MRI — for neurologic symptoms; detects silent cerebral emboli in up to 80% of left-sided IE
- CT abdomen/pelvis — for splenic/renal infarcts, abscesses [6]
- Chest CT — for septic pulmonary emboli in right-sided IE
The following figure illustrates an integrated imaging algorithm for suspected IE:
13. Special Tests
Diagnostic scoring
- 2023 Duke-ISCVID Criteria — definite IE requires 2 major criteria, or 1 major + 3 minor, or 5 minor criteria; more sensitive than modified Duke criteria (84.2% vs 74.9%) without significant loss of specificity [2][4]
- Intraoperative inspection is now a new major criterion [4]
Point-of-care
- Bedside TTE (limited but can identify large vegetations in the ED)
- Point-of-care lactate (sepsis assessment)
Specialty tests
- Histopathology of resected valve tissue or embolized vegetation (definitive diagnosis) [8]
- In situ hybridization on valve tissue [2][4]
14. ECG
- New conduction abnormalities — PR prolongation, new bundle branch block, or complete heart block strongly suggest perivalvular/aortic root abscess, especially in aortic valve IE [7-8]
- Obtain baseline ECG and monitor serially
- ST changes may indicate coronary embolization (rare)
- Tachycardia (sepsis, heart failure)
- Low voltage or electrical alternans if pericardial effusion develops
15. Assessment
Severity stratification
- Acute IE — rapid onset, high fever, sepsis, S. aureus predominant; high mortality (~25–40% for S. aureus IE) [1][3]
- Subacute IE — indolent course, viridans streptococci or enterococci; lower mortality but delayed diagnosis common [1][12]
- Complicated IE — heart failure, abscess, embolic events, persistent bacteremia; requires urgent surgical evaluation [7-8]
Typical vs. atypical presentations
- Classic triad of fever + murmur + positive blood cultures is present in a minority [12]
- Elderly/immunocompromised patients may be afebrile with nonspecific symptoms [6]
- Right-sided IE (IVDU) may lack peripheral embolic phenomena but presents with septic pulmonary emboli (cough, pleuritic pain, bilateral nodular infiltrates) [12]
Complications
- Heart failure (most common indication for surgery, ~27% of cases) [2]
- Systemic embolization (~20–50%, highest in first 2 weeks) [5]
- Stroke (~15–20% of left-sided IE) [6]
- Mycotic aneurysm, perivalvular abscess, intracardiac fistula [7][9]
- Glomerulonephritis, renal failure [9]
16. Treatment Plan
Initial stabilization
- ABCs, hemodynamic resuscitation, vasopressors if septic shock
- Draw blood cultures immediately, then start empiric IV antibiotics [2][6]
- Source control: remove infected intravascular catheters, evaluate for abscess drainage [6]
Empiric antibiotic regimens (see Medications section above) [6][10]
Definitive therapy: Organism-directed based on culture and susceptibility results; minimum 4 weeks for NVE, 6 weeks for PVE (enterococcal IE: ≥6 weeks regardless) [6]
Oral step-down: Three RCTs support transition to oral therapy in the continuation phase for stable patients with left-sided NVE or PVE who are clinically improving, afebrile, with negative blood cultures, and no longer require surgery [2][10]
Surgical indications (early surgery during initial hospitalization):
- Heart failure from valve dysfunction [7-8]
- Uncontrolled infection: abscess, fistula, enlarging vegetation, persistent bacteremia >5–7 days [7-8]
- Prevention of embolism: recurrent emboli with persistent vegetations, or vegetations >10 mm after embolic event [7]
- Fungal or highly resistant organisms [7]
- Prosthetic valve dehiscence [7-8]
Timing of surgery
- Emergency (within 24 hours): refractory pulmonary edema, cardiogenic shock [7]
- Urgent (within days): most other surgical indications [7]
- Stroke is NOT a contraindication to surgery unless there is extensive neurologic damage or intracranial hemorrhage [8]
Multidisciplinary team: Infectious disease, cardiology, cardiothoracic surgery, neurology (if neurologic complications) — early involvement is associated with improved survival [6][8][13]
17. Disposition
Admission criteria
- All patients with suspected or confirmed IE require hospitalization for IV antibiotics, monitoring, and workup [2][6]
- ICU admission for hemodynamic instability, septic shock, acute heart failure, or neurologic emergencies
Transfer criteria
Observation
Discharge criteria
- Clinically stable, afebrile, blood cultures negative, no surgical indication, and appropriate oral step-down regimen available (per POET trial criteria) — may complete therapy as outpatient with OPAT or oral antibiotics [2][10]
- Ensure reliable follow-up and compliance
18. Follow Up / Return Precautions
Follow-up timing
- Repeat echocardiography at completion of therapy to establish new baseline [8]
- Infectious disease follow-up within 1–2 weeks of discharge
- Cardiology follow-up for valve function monitoring
- Dental evaluation for source control [3]
Return precautions — instruct patients to seek immediate care for:
- Recurrent fever, chills, or rigors
- New neurologic symptoms (weakness, speech difficulty, severe headache)
- Worsening dyspnea, chest pain, or lower extremity swelling
- Skin lesions on palms/soles or painful fingertip nodules
- Hematuria or decreased urine output
Expected recovery
- Clinical improvement typically within 5–7 days of appropriate antibiotics [2]
- Total treatment duration: 4–6 weeks minimum
- Recurrence rate: ~2–6% within 1 year; higher with ongoing IV drug use [11]
Long-term considerations
- Antibiotic prophylaxis for future dental procedures in patients with prosthetic valves, prior IE, certain congenital heart diseases, or cardiac transplant with valvulopathy per AHA guidelines [8][12]
- Substance use disorder treatment and harm reduction for patients with drug use-associated IE [11]
- Colonoscopy if S. gallolyticus (formerly S. bovis) is isolated — associated with colorectal neoplasia [1]
References
1. Native-Valve Infective Endocarditis. — Chambers HF, Bayer AS. The New England Journal of Medicine. 2020.
2. Infective Endocarditis. — Li M, Kim JB, Sastry BKS, Chen M. Lancet. 2024.
3. Management Considerations in Infective Endocarditis: A Review. — Wang A, Gaca JG, Chu VH. The Journal of the American Medical Association. 2018.
4. The 2023 Duke-International Society for Cardiovascular Infectious Diseases Criteria for Infective Endocarditis: Updating the Modified Duke Criteria. — Fowler VG, Durack DT, Selton-Suty C, et al. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 2023.
5. Infective endocarditis complicated by embolic events: Pathogenesis and predictors. — Hu W, Wang X, Su G. Clinical Cardiology. 2021.
6. Infective Endocarditis: Diagnosis and Treatment. — Nohria R, Romaine A, Garcia-Sampson G. American Family Physician. 2026.
7. Challenges in Infective Endocarditis. — Cahill TJ, Baddour LM, Habib G, et al. Journal of the American College of Cardiology. 2017.
8. 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. — Otto CM, Nishimura RA, Bonow RO, et al. Journal of the American College of Cardiology. 2021.
9. Recent Insights Into Native Valve Infective Endocarditis: JACC Focus Seminar 4/4. — Dayer MJ, Quintero-Martinez JA, Thornhill MH, et al. Journal of the American College of Cardiology. 2024.
10. Guidelines for Diagnosis and Management of Infective Endocarditis in Adults: A WikiGuidelines Group Consensus Statement. — McDonald EG, Aggrey G, Aslan AT, et al. JAMA Network Open. 2023.
11. Diagnosis and Management of Infective Endocarditis in People Who Inject Drugs: JACC State-of-the-Art Review. — Yucel E, Bearnot B, Paras ML, et al. Journal of the American College of Cardiology. 2022.
12. Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications: A Scientific Statement for Healthcare Professionals From the American Heart Association. — Baddour LM, Wilson WR, Bayer AS, et al. Circulation. 2015.
13. Staphylococcus Aureus Infective Endocarditis: JACC Patient Pathways. — Grapsa J, Blauth C, Chandrashekhar YS, et al. Journal of the American College of Cardiology. 2022.