1. History
- Onset and tempo: Acute vs. subacute presentation — acute IE (typically S. aureus) presents with sudden high fever, rigors, and rapid deterioration; subacute IE (viridans streptococci, enterococci) evolves over weeks to months with nonspecific symptoms [1-2]
- Key HPI questions:
- Fever pattern, duration, and response to antipyretics
- Rigors, chills, night sweats, diaphoresis
- Dyspnea, orthopnea, lower extremity edema (heart failure symptoms)
- Neurologic symptoms: focal weakness, vision changes, headache, confusion (embolic stroke, mycotic aneurysm)
- Back pain, arthralgias, myalgias
- Weight loss, fatigue, malaise, anorexia
- Hematuria (renal emboli or glomerulonephritis)
- Painful lesions on fingers/toes (Osler nodes) or painless lesions on palms/soles (Janeway lesions)
- Timing: Ask about recent dental procedures, invasive procedures, hospitalizations, or IV line placement within prior weeks [3-4]
- Important negatives: No recent antibiotic use (affects blood culture yield), no prior cardiac surgery, no injection drug use
2. Alarm Features
- Acute heart failure: New dyspnea, pulmonary edema, cardiogenic shock from acute valvular regurgitation — requires emergency surgery within 24 hours [5-6]
- Neurologic events: Sudden focal deficits (embolic stroke in ~20–40% of left-sided IE), intracranial hemorrhage, meningitis, brain abscess [3]
- Septic shock / hemodynamic instability
- Persistent bacteremia >5–7 days despite appropriate antibiotics — indicates uncontrolled infection [5]
- New conduction abnormalities (heart block) — suggests perivalvular abscess extending into the conduction system [5]
- Splenic or renal infarction, mycotic aneurysm, septic pulmonary emboli (right-sided IE)
- Large mobile vegetations >10 mm, especially on the anterior mitral leaflet — high embolic risk [5][7]
3. Medications
Empiric therapy
- Native valve: Vancomycin + ceftriaxone is a reasonable empiric regimen [1][4]
- Prosthetic valve: Vancomycin + cefepime or piperacillin-tazobactam (antipseudomonal coverage) [4]
- If GI/odontogenic source suspected: ampicillin-sulbactam may replace ceftriaxone [4]
Definitive therapy (organism-directed)
- MSSA: Nafcillin/oxacillin 12 g/day IV ÷ 4–6 doses × 4–6 weeks; cefazolin 6 g/day ÷ 3 doses is an alternative. Beta-lactams preferred over vancomycin for higher cure rates [1][4][7]
- MRSA: Vancomycin (target AUC 400–600) or daptomycin 10 mg/kg/day × 6 weeks [1]
- Viridans streptococci (penicillin MIC ≤0.12): Penicillin G or ceftriaxone × 4 weeks; 2-week short course with gentamicin is an option in select patients [1]
- Enterococci: Ampicillin + ceftriaxone × 6 weeks (preferred for high-level aminoglycoside resistance or renal risk); ampicillin + gentamicin is an alternative [1]
Duration: ≥4 weeks for native valve IE; ≥6 weeks for prosthetic valve IE and enterococcal IE [4]
Medication cautions
- Aminoglycosides: Avoid in elderly, renal disease, or concurrent nephrotoxic agents; limit to ≤2 weeks [1]
- Rifampin: Reserve for definitive therapy in prosthetic valve IE; do not use empirically [8]
- Daptomycin: Inactivated by pulmonary surfactant — do not use for pneumonia/pulmonary infections
- Combination nafcillin + gentamicin or rifampin for MSSA NVE does not improve outcomes and increases toxicity [1]
The following table summarizes antibiotic regimens by pathogen:
4. Diet
- No specific dietary triggers or restrictions unique to endocarditis
- Adequate nutrition is critical during prolonged hospitalization and IV antibiotic therapy — consider nutritional support for malnourished or cachectic patients
- Hydration: Maintain adequate hydration, particularly with nephrotoxic antibiotics (vancomycin, gentamicin)
- Patients with heart failure from valvular dysfunction should follow sodium and fluid restriction
5. Review of Systems
- Cardiovascular: Dyspnea, orthopnea, PND, palpitations, chest pain, syncope
- Neurologic: Headache, focal weakness, vision changes, confusion, seizures
- Musculoskeletal: Back pain (spondylodiscitis), arthralgias, myalgias
- Dermatologic: Petechiae, painful finger/toe nodules, painless palmar/plantar lesions, splinter hemorrhages
- Renal/GU: Hematuria, flank pain, decreased urine output
- Pulmonary: Cough, hemoptysis, pleuritic chest pain (right-sided IE with septic pulmonary emboli)
- Ophthalmologic: Visual changes (Roth spots)
- Constitutional: Fever, weight loss, night sweats, fatigue
6. Collateral History and Family History
- Collateral: Injection drug use practices (frequency, injection sites, needle sharing, water source), recent dental work, recent hospitalization or procedures, indwelling catheters, prior episodes of IE
- Social context: Housing status (homelessness associated with Bartonella quintana), farm animal exposure (Coxiella burnetii) [1]
- Family history: Congenital heart disease, rheumatic heart disease
- Medication adherence history: Critical for planning outpatient parenteral antibiotic therapy (OPAT) or oral step-down
7. Risk Factors
- Cardiac: Prior IE (strongest risk factor), prosthetic heart valve, valvular heart disease (degenerative, rheumatic, bicuspid aortic valve), congenital heart disease, hypertrophic cardiomyopathy, CIEDs, ventricular assist devices [1-3]
- Non-cardiac: IV drug use, chronic hemodialysis, indwelling intravascular catheters, poor dentition/dental pathology, immunosuppression, diabetes, chronic liver disease, malignancy, recent hospitalization >48 hours [1-2]
- Demographic: Age >60, male sex [2]
- Microbiologic: S. aureus bacteremia carries ~25–30% risk of concurrent IE
8. Differential Diagnosis
- Sepsis from other sources (pneumonia, UTI, intra-abdominal abscess) — most common mimic; distinguished by echocardiographic findings and persistent bacteremia
- Non-bacterial thrombotic (marantic) endocarditis — associated with malignancy, SLE (Libman-Sacks); culture-negative, no fever
- Rheumatic fever — migratory polyarthritis, erythema marginatum, Sydenham chorea; Jones criteria; ASO titers
- Systemic vasculitis (polyarteritis nodosa, granulomatosis with polyangiitis) — can mimic embolic phenomena
- Atrial myxoma — intracardiac mass on echo, embolic events, constitutional symptoms; distinguished by tissue pathology
- Antiphospholipid syndrome — thrombotic events, valve thickening
- Fever of unknown origin with culture-negative bacteremia — consider Coxiella, Bartonella, Tropheryma whipplei, fungi [1]
9. Past Medical History
- Prior endocarditis — recurrence risk is significant
- Valvular disease: Rheumatic heart disease, mitral valve prolapse, degenerative aortic stenosis, bicuspid aortic valve
- Prosthetic valves or cardiac devices — early PVE (<12 months) vs. late PVE have different microbiology
- Congenital heart disease (VSD, unrepaired cyanotic lesions)
- Chronic kidney disease / hemodialysis
- Diabetes, liver cirrhosis, HIV/immunosuppression
- History of IV drug use — duration, current status, prior treatment
- Recent surgical or dental procedures
10. Physical Exam
- Vitals: Fever (≥38°C in ~78% of cases), tachycardia, hypotension (septic/cardiogenic shock), tachypnea [3]
- Cardiac: New or changing murmur (64.5% of cases) — particularly new aortic regurgitation murmur; signs of heart failure (JVD, S3, pulmonary crackles, peripheral edema) [3-4]
- Skin/extremities:
- Petechiae (conjunctival, oral mucosa, extremities)
- Janeway lesions — painless erythematous macules on palms/soles (septic emboli)
- Osler nodes — painful nodules on finger/toe pads (immune complex)
- Splinter hemorrhages (linear subungual)
- Eyes: Roth spots on fundoscopy (white-centered retinal hemorrhages)
- Abdomen: Splenomegaly (present in ~15–30% of subacute IE), LUQ tenderness (splenic infarct/abscess)
- Neurologic: Focal deficits (embolic stroke), meningismus, altered mental status
- Injection sites: Track marks, skin abscesses, cellulitis in PWID
11. Lab Studies
- Blood cultures: The cornerstone of diagnosis — obtain ≥3 sets from separate venipuncture sites, ideally 30 minutes apart, before starting antibiotics. ~90–95% of native valve IE is culture-positive [1]
- CBC: Leukocytosis (acute), anemia of chronic disease (subacute), thrombocytopenia (DIC)
- Inflammatory markers: Elevated ESR, CRP, procalcitonin
- BMP/CMP: Creatinine (renal emboli, drug nephrotoxicity, glomerulonephritis), electrolytes
- Urinalysis: Hematuria, proteinuria, RBC casts (immune-complex glomerulonephritis)
- Rheumatoid factor: Positive in ~50% of subacute IE (minor Duke criterion)
- Complement levels: May be low (immune complex consumption)
- Coagulation studies: PT/INR, aPTT (DIC screening)
- Lactate: If septic shock suspected
- Culture-negative workup: PCR for Coxiella burnetii, Bartonella spp., Tropheryma whipplei; Coxiella phase I IgG titer; Bartonella IFA IgG/IgM [1][4][9]
- Monitoring: Repeat blood cultures every 24–48 hours until clearance; vancomycin AUC/trough levels; weekly CBC, BMP for drug toxicity
12. Imaging
- First-line: Transthoracic echocardiography (TTE) — sensitivity ~70% for native valves, ~50% for prosthetic valves; specificity ~94% [4][7]
- Transesophageal echocardiography (TEE): Sensitivity ~90–96% for both native and prosthetic valves. Indicated when: [4-5][7]
- TTE is negative or equivocal but clinical suspicion remains high
- Prosthetic valve or intracardiac device
- Suspected complications (abscess, fistula, perforation)
- S. aureus bacteremia
- Cardiac CT: Useful for detecting abscesses, pseudoaneurysms, and surgical planning; less sensitive for small (<4 mm) vegetations [4]
- ¹⁸F-FDG PET/CT: Incorporated into 2023 Duke-ISCVID criteria; particularly valuable for prosthetic valve IE, CIED infections, and culture-negative cases [3][9]
- Brain MRI: For neurologic symptoms — detects silent cerebral emboli in up to 60–80% of left-sided IE even without symptoms
- CT abdomen/pelvis: Splenic abscess/infarct, renal infarct, mycotic aneurysm
- CT chest: Septic pulmonary emboli in right-sided IE
- When imaging is unnecessary: If TTE is clearly positive with uncomplicated native valve IE and low clinical suspicion for complications, TEE may not add value
The following figure illustrates the diagnostic algorithm for IE:
13. Special Tests
- Modified Duke Criteria / 2023 Duke-ISCVID Criteria: The standard diagnostic framework — classifies IE as definite, possible, or rejected based on major criteria (positive blood cultures, imaging evidence of endocardial involvement) and minor criteria (predisposition, fever, vascular phenomena, immunologic phenomena, supportive microbiology) [3][7][9]
- Definite IE: 2 major criteria, or 1 major + 3 minor, or 5 minor criteria
- Possible IE: 1 major + 1 minor, or 3 minor criteria
- Intraoperative inspection: Added as a new major clinical criterion in the 2023 Duke-ISCVID update [9]
- Point-of-care ultrasound (POCUS): Can identify large vegetations, pericardial effusion, and gross valvular dysfunction at bedside in the ED
- Dental evaluation: Assess for dental abscess or periodontal disease as source
14. ECG
- Indications: Obtain on all patients with suspected IE
- New PR prolongation or heart block: Highly concerning for perivalvular/aortic root abscess extending into the conduction system — this is a surgical emergency [3][5]
- ST changes: May indicate coronary embolization causing myocardial infarction (rare)
- Atrial fibrillation: May develop secondary to atrial dilation from valvular regurgitation
- Serial ECGs recommended to monitor for evolving conduction abnormalities
15. Assessment
Severity stratification
- In-hospital mortality: ~15–20% overall; higher with S. aureus (~25–40%), prosthetic valve IE, and left-sided IE [3]
- 1-year mortality: ~30% [3]
- Typical presentation: Fever + new murmur + positive blood cultures with a typical organism
- Atypical presentations: Subacute with only fatigue and weight loss (elderly, immunocompromised); initial presentation as stroke, renal infarct, or spondylodiscitis without obvious cardiac symptoms; culture-negative IE [4]
- Complications to anticipate: Heart failure (most common indication for surgery), embolic events (stroke, splenic/renal infarcts), perivalvular abscess, mycotic aneurysm, renal failure, septic shock [3]
16. Treatment Plan
Initial stabilization
- ABCs, IV access, hemodynamic monitoring
- Obtain blood cultures before antibiotics, then start empiric IV antibiotics promptly in acute presentations; in subacute presentations, may wait for culture results if hemodynamically stable [3]
- Fluid resuscitation and vasopressors for septic shock
Empiric antibiotics
- Native valve: Vancomycin + ceftriaxone [1][4]
- Prosthetic valve: Vancomycin + cefepime or piperacillin-tazobactam [4]
- Narrow to definitive therapy once cultures and sensitivities return [4]
Source control
- Remove infected intravascular catheters, lines, and devices
- Evaluate for abscess drainage [4]
Surgical indications (Class I): [5-6]
- Heart failure from valve dysfunction
- Perivalvular abscess, heart block, fistula, destructive penetrating lesions
- Persistent bacteremia/fever >5–7 days on appropriate antibiotics
- Fungal or highly resistant organisms
- Recurrent emboli with persistent vegetations despite antibiotics
Surgical timing: [6][11]
- Emergency (within 24 hours): Refractory pulmonary edema or cardiogenic shock
- Urgent (within 3–5 days): Uncontrolled infection, large vegetations with embolic events
- Elective: After 1–2 weeks of antibiotics in stable patients
Oral step-down (POET trial): In stable patients who are afebrile with negative blood cultures and no surgical indications, transition to oral antibiotics during the continuation phase (after ≥7–10 days IV) may be considered [3-4]
Multidisciplinary team: Infectious disease, cardiology, and cardiothoracic surgery should be involved early — associated with improved survival [4][11]
17. Disposition
- All patients with confirmed or suspected IE require hospital admission — typically to a telemetry or ICU bed depending on hemodynamic status
- ICU admission criteria: Septic shock, cardiogenic shock, acute heart failure, new neurologic deficits, need for vasopressors or mechanical circulatory support
- Transfer to tertiary center: If surgical capability is not available and surgical indications are present or anticipated [12]
- Discharge criteria: Afebrile, blood cultures negative, hemodynamically stable, no surgical indications, reliable outpatient IV access (PICC line) and OPAT infrastructure in place, or meeting criteria for oral step-down
- Observation: Not appropriate — IE requires inpatient management
Specialist consultation triggers
- Infectious disease: All cases [4]
- Cardiothoracic surgery: All complicated IE, large vegetations, prosthetic valve IE
- Cardiology: Echocardiographic assessment, hemodynamic management
- Neurology/neurosurgery: Stroke, intracranial hemorrhage, mycotic aneurysm
- Addiction medicine: PWID
18. Follow Up / Return Precautions
- Follow-up timing: Clinical and laboratory reassessment within 1–2 weeks of discharge; repeat echocardiography at completion of antibiotic therapy to establish new baseline; follow-up at 1, 3, 6, and 12 months [11]
- Symptoms requiring immediate reassessment:
- Recurrent fever or chills
- New neurologic symptoms (weakness, speech difficulty, severe headache)
- Worsening dyspnea, chest pain, or edema
- Signs of line infection (erythema, drainage at PICC site)
- Patient counseling:
- Complete the full antibiotic course — do not stop early
- Antibiotic prophylaxis before dental procedures is recommended for patients with a history of IE [4]
- Maintain meticulous oral and skin hygiene to reduce reinfection risk [4]
- Avoid IV drug use; connect with addiction medicine and harm reduction services if applicable
- Expected recovery: Clinical improvement typically within 5–7 days of effective antibiotics; full antibiotic course is 4–6 weeks; recurrence risk is ~2–6% per year
- Long-term monitoring: Surveillance for late valve dysfunction, heart failure, and recurrent IE
References
1. Native-Valve Infective Endocarditis. — Chambers HF, Bayer AS. The New England Journal of Medicine. 2020.
2. Management Considerations in Infective Endocarditis: A Review. — Wang A, Gaca JG, Chu VH. The Journal of the American Medical Association. 2018.
3. Infective Endocarditis. — Li M, Kim JB, Sastry BKS, Chen M. Lancet. 2024.
4. Infective Endocarditis: Diagnosis and Treatment. — Nohria R, Romaine A, Garcia-Sampson G. American Family Physician. 2026.
5. 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.
6. Challenges in Infective Endocarditis. — Cahill TJ, Baddour LM, Habib G, et al. Journal of the American College of Cardiology. 2017.
7. 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.
8. 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.
9. 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.
10. Best Practices for Imaging Cardiac Device-Related Infections and Endocarditis: A JACC: Cardiovascular Imaging Expert Panel Statement. — Dilsizian V, Budde RPJ, Chen W, et al. JACC. Cardiovascular Imaging. 2022.
11. Surgical Implications of the 2023 ESC Endocarditis Guidelines Endorsed by EACTS: Bridging Guidelines and Practice. — de la Cuesta M, Marin-Cuartas M, de Waha S, et al. European Journal of Cardio-Thoracic Surgery : Official Journal of the European Association for Cardio-Thoracic Surgery. 2025.
12. Staphylococcus Aureus Infective Endocarditis: JACC Patient Pathways. — Grapsa J, Blauth C, Chandrashekhar YS, et al. Journal of the American College of Cardiology. 2022.