Infective Endocarditis (IE)

A 45-year-old man presents to the emergency department with a 1-week history of fever, chills, pleuritic chest pain, and shortness of breath. He reports fatigue and decreased appetite. His medical history is significant for injection drug use. On examination, his temperature is 39°C, pulse is 110/min, and blood pressure is 100/60 mmHg. Cardiac auscultation reveals a holosystolic murmur best heard at the left lower sternal border that increases with inspiration. Multiple painless erythematous lesions on the palms and linear hemorrhages under the fingernails are noted. Laboratory studies show leukocytosis. Blood cultures grow Staphylococcus aureus. Chest imaging demonstrates multiple nodular infiltrates consistent with septic pulmonary emboli. Transesophageal echocardiography reveals a mobile vegetation on the tricuspid valve. Diagnosis?

Diagnosis is acute right-sided infective endocarditis involving the tricuspid valve, caused by Staphylococcus aureus and complicated by septic pulmonary emboli.

The combination of injection drug use, S. aureus bacteremia, tricuspid regurgitation, tricuspid vegetation, and septic pulmonary emboli is highly characteristic of right-sided infective endocarditis.

1. Definition

Infective endocarditis is an infection of the endocardial surface of the heart, most commonly involving a native or prosthetic valve, although implanted intracardiac material may also be involved.

Infected vegetations contain:

1.      Fibrin

2.      Platelets

3.      Microorganisms

4.      Inflammatory material

IE can cause:

1.      Valve destruction and regurgitation

2.      Persistent bacteremia

3.      Embolic complications

4.      Abscess formation

5.      Immune-mediated manifestations

6.      Heart failure

2. Risk Factors

Important risk factors include:

1.      Injection drug use

2.      Previous infective endocarditis

3.      Prosthetic heart valves or prosthetic valve-repair material

4.      Congenital heart disease

5.      Degenerative valvular disease

6.      Cardiac implantable electronic devices

7.      Indwelling intravascular catheters

8.      Hemodialysis

9.      Poor oral health

10.  Immunosuppression

In people who inject drugs, IE commonly involves the tricuspid valve, and S. aureus is the predominant pathogen.

3. Pathophysiology

1.      Bacteremia introduces microorganisms into the bloodstream.

2.      Microorganisms adhere to susceptible endocardial surfaces or intracardiac prosthetic material.

3.      Platelet and fibrin deposition promotes formation of an infected vegetation.

4.      Bacteria multiply within the vegetation, producing sustained or recurrent bacteremia.

5.      Progressive infection can cause:

1.      Valve destruction

2.      Regurgitation

3.      Perivalvular extension

4.      Abscess formation

6.      Fragments of vegetation may embolize.

Right-sided IE produces emboli into the pulmonary circulation, causing:

1.      Septic pulmonary emboli

2.      Pulmonary infarction

3.      Pulmonary abscesses

4.      Pleuritic chest pain

5.      Hemoptysis

6.      Respiratory failure in severe cases

S. aureus is highly virulent and can infect previously normal valves.

4. Microbiology

4.1 Common Pathogens

Important causes include:

1.      Staphylococcus aureus

2.      Viridans group streptococci

3.      Enterococcus faecalis

4.      Streptococcus gallolyticus

5.      Coagulase-negative staphylococci, particularly with prosthetic material

6.      HACEK organisms

4.2 Injection Drug Use

In right-sided IE associated with injection drug use:

1.      S. aureus is the predominant organism

2.      MRSA should be considered depending on local epidemiology and patient history

3.      Gram-negative organisms and fungi occur but are much less common

4.3 Culture-Negative IE

The most common reason for culture-negative IE is antibiotic administration before blood cultures are obtained.

Important causes of true blood culture-negative IE include:

1.      Coxiella burnetii

2.      Bartonella species

3.      Tropheryma whipplei

4.      Fungi and other difficult-to-culture organisms

Modern automated blood-culture systems generally recover HACEK organisms, so HACEK organisms should not automatically be classified as culture-negative pathogens.

4.4 Important Association

Streptococcus gallolyticus bacteremia or endocarditis is associated with colorectal neoplasia and should prompt appropriate colorectal evaluation.

5. Clinical Features

5.1 General Features

1.      Fever

2.      Chills

3.      Malaise

4.      Fatigue

5.      Anorexia

6.      Weight loss

7.      Night sweats

5.2 Cardiac Features

1.      New or changing regurgitant murmur

2.      Valve destruction

3.      Heart failure

4.      Conduction abnormalities when infection extends into perivalvular tissue

With tricuspid regurgitation:

1.      The murmur is typically holosystolic

2.      It is best heard at the left lower sternal border

3.      It becomes louder with inspiration, known as the Carvallo sign

5.3 Right-Sided IE

Right-sided IE commonly produces pulmonary manifestations:

1.      Pleuritic chest pain

2.      Dyspnea

3.      Cough

4.      Hemoptysis

5.      Multiple peripheral pulmonary nodules

6.      Septic pulmonary emboli

5.4 Vascular Phenomena

Janeway lesions

1.      Painless erythematous or hemorrhagic lesions

2.      Usually occur on the palms or soles

3.      Represent vascular or septic microembolic phenomena

Splinter hemorrhages

1.      Linear hemorrhages beneath the nails

2.      Support the diagnosis in the appropriate clinical setting

3.      Are not specific for IE

5.5 Immunologic Phenomena

1.      Osler nodes

1.      Painful nodules on the fingers or toes

2.      Roth spots

3.      Immune complex glomerulonephritis

4.      Positive rheumatoid factor may occur

Janeway lesions are typically painless, whereas Osler nodes are painful.

6. Diagnosis

Diagnosis combines:

1.      Clinical features

2.      Blood cultures

3.      Echocardiography

4.      Additional microbiologic and imaging findings

6.1 Blood Cultures

1.      Obtain blood cultures before antibiotics whenever clinically feasible.

2.      For suspected IE, obtain at least 3 sets of blood cultures from peripheral veins before antimicrobial therapy.

3.      Each set should contain aerobic and anaerobic bottles with adequate blood volume.

4.      Antibiotic therapy should not be delayed in a patient with sepsis or hemodynamic instability merely to obtain additional cultures.

5.      Repeat blood cultures during treatment to document clearance of bacteremia, particularly with S. aureus.

6.2 Echocardiography

Transthoracic echocardiography is the first-line echocardiographic study in suspected IE.

TEE is more sensitive for many forms of IE and is particularly useful when:

1.      TTE is negative or inconclusive despite persistent clinical suspicion

2.      Prosthetic valves are present

3.      Intracardiac devices are present

4.      Perivalvular complications are suspected

5.      Left-sided involvement requires further evaluation

In isolated native tricuspid IE, TTE may visualize vegetations well because of the anterior position of the tricuspid valve.

Therefore, TEE should not be described as the universal first-line gold-standard test.

In this patient, TEE demonstrates a mobile tricuspid vegetation, strongly supporting the diagnosis.

7. 2023 Duke-ISCVID Diagnostic Criteria

The contemporary Duke-ISCVID framework classifies IE using major and minor criteria.

7.1 Major Criteria

Major criteria include:

1.      Microbiologic evidence

1.      Typical IE organisms, including S. aureus, isolated from at least 2 separate blood-culture sets

2.      Certain specific molecular or serologic findings for fastidious organisms

2.      Imaging evidence

1.      Vegetation

2.      Abscess

3.      Pseudoaneurysm

4.      Intracardiac fistula

5.      Valve or leaflet perforation or aneurysm

6.      Significant new valvular regurgitation

7.      Relevant cardiac CT or FDG-PET/CT findings in appropriate settings

3.      Direct surgical evidence of IE may also constitute a major criterion in selected circumstances.

7.2 Minor Criteria

Minor criteria include:

1.      Predisposing condition, including injection drug use

2.      Fever >38°C

3.      Vascular phenomena, including:

1.      Septic pulmonary infarcts

2.      Arterial emboli

3.      Janeway lesions

4.      Mycotic aneurysm

5.      Intracranial hemorrhage

4.      Immunologic phenomena:

1.      Osler nodes

2.      Roth spots

3.      Immune complex glomerulonephritis

4.      Rheumatoid factor

5.      Microbiologic evidence that does not fulfill a major criterion

7.3 Definite Clinical IE

Definite IE can be established by:

1.      2 major criteria

2.      1 major + 3 minor criteria

3.      5 minor criteria

In this patient, a tricuspid vegetation fulfills a major imaging criterion. If S. aureus is isolated from at least 2 separate blood-culture sets, it also fulfills a major microbiologic criterion, establishing definite IE by two major criteria.

8. Additional Evaluation

Evaluate:

1.      Complete blood count

2.      Renal function

3.      Liver function

4.      Inflammatory markers

5.      Urinalysis for hematuria or proteinuria

6.      ECG

7.      Serial blood cultures

8.      Chest CT when septic pulmonary emboli are suspected

9.      Other organ imaging if metastatic infection is clinically suspected

A new atrioventricular block or other new conduction disturbance should raise concern for perivalvular extension or abscess, particularly in aortic valve IE.

9. Management

Management should involve a multidisciplinary Endocarditis Team, typically including cardiology, infectious diseases, microbiology, cardiac surgery when appropriate, and addiction medicine for patients with injection drug use.

9.1 Initial Stabilization

1.      Assess airway, breathing, and circulation.

2.      Establish IV access.

3.      Treat hypoxemia when present.

4.      Manage sepsis and hypotension with appropriate fluid resuscitation and vasopressors when required.

5.      Obtain blood cultures before antimicrobial therapy whenever feasible.

9.2 Empiric Antimicrobial Therapy

Empiric IV therapy should be initiated promptly after blood cultures are obtained.

The regimen depends on:

1.      Native versus prosthetic valve

2.      Community versus healthcare-associated infection

3.      Local antimicrobial resistance

4.      Previous antibiotic exposure

5.      Patient-specific risk factors

For suspected right-sided IE in a person who injects drugs, empiric therapy should provide reliable S. aureus coverage, including MRSA when appropriate.

Once culture and susceptibility results are available, therapy should be narrowed.

9.3 Targeted S. aureus Therapy

MSSA native-valve IE

Preferred agents include an antistaphylococcal beta-lactam such as:

1.      Oxacillin or nafcillin

2.      Cloxacillin or flucloxacillin where commonly used

3.      Cefazolin as an effective alternative

Beta-lactams are preferred over vancomycin for MSSA when they can be safely administered.

MRSA native-valve IE

Major treatment options include:

1.      Vancomycin

2.      Daptomycin

Treatment should be individualized with infectious-disease consultation.

Routine aminoglycoside addition is not recommended for staphylococcal native-valve IE because nephrotoxicity outweighs demonstrated benefit.

9.4 Duration

Treatment duration depends on:

1.      Pathogen

2.      Antimicrobial susceptibility

3.      Valve type

4.      Vegetation size

5.      Clinical and microbiologic response

6.      Presence of cardiac or extracardiac complications

7.      Metastatic infection

8.      Prosthetic material

Most patients with staphylococcal native-valve IE require approximately 4 to 6 weeks of effective antimicrobial therapy.

A 2-week regimen of oxacillin or cloxacillin without gentamicin may be considered in carefully selected patients with uncomplicated isolated right-sided MSSA IE when relevant criteria are satisfied, including:

1.      MSSA infection

2.      Prompt clinical and microbiologic response

3.      Vegetation ≤20 mm

4.      No empyema

5.      No metastatic infection outside the lungs

6.      No major cardiac or extracardiac complication

7.      No prosthetic valve or prosthetic intracardiac material

8.      No left-sided IE

9.      No severe immunosuppression

Septic pulmonary emboli alone do not automatically exclude a short-course regimen in otherwise uncomplicated right-sided MSSA IE.

In this patient, the organism is reported only as S. aureus, and the MSSA versus MRSA status, vegetation size, and early clinical and microbiologic response are not yet known. Therefore, treatment duration cannot yet be definitively selected.

10. Septic Pulmonary Emboli

Septic pulmonary emboli are a characteristic complication of tricuspid IE.

Clinical manifestations include:

1.      Fever

2.      Pleuritic chest pain

3.      Dyspnea

4.      Cough

5.      Hemoptysis

Chest CT may show:

1.      Multiple peripheral nodules

2.      Cavitary nodules

3.      Wedge-shaped peripheral opacities

4.      Pulmonary infarcts

5.      Abscess formation

Management primarily consists of:

1.      Effective antimicrobial therapy

2.      Source control when indicated

3.      Respiratory support when required

11. Indications for Intervention in Right-Sided IE

Most uncomplicated right-sided IE can be managed medically.

Surgery should be considered in situations such as:

1.      Persistent bacteremia or sepsis despite at least 7 days of appropriate antimicrobial therapy

2.      Severe tricuspid regurgitation causing right ventricular dysfunction or right-sided heart failure that does not respond adequately to diuretic therapy

3.      Residual tricuspid vegetation >20 mm after recurrent septic pulmonary emboli

4.      Respiratory insufficiency requiring ventilatory support after recurrent pulmonary emboli

5.      Concomitant left-sided IE

When surgery is required, tricuspid valve repair is generally preferred over valve replacement when feasible.

An isolated vegetation or septic pulmonary emboli alone do not automatically mandate surgery.

The 2026 AHA statement also recognizes percutaneous mechanical aspiration as an emerging option for selected high-surgical-risk patients with right-sided IE who have an inadequate response to antimicrobial therapy. Evidence remains more limited than for established medical and surgical approaches.

12. Monitoring

Monitor:

1.      Serial blood cultures until bacteremia clears

2.      Temperature

3.      Hemodynamic status

4.      Renal function

5.      Complete blood count

6.      Drug toxicity

7.      Respiratory status

8.      Signs of worsening tricuspid regurgitation or right-sided heart failure

9.      New embolic complications

10.  Evidence of metastatic infection

Persistent S. aureus bacteremia despite appropriate therapy should prompt evaluation for:

1.      Inadequate source control

2.      Perivalvular infection

3.      Metastatic infection

4.      Infected vascular or intracardiac devices

5.      Need for procedural intervention

13. Prevention

Prevention includes:

1.      Good oral hygiene and regular dental care

2.      Appropriate management of intravascular catheters and implanted devices

3.      Addiction medicine consultation and evidence-based treatment for substance use disorder

4.      Harm-reduction strategies for people who inject drugs

Antibiotic prophylaxis is reserved for patients at highest risk of adverse outcomes from IE who undergo qualifying dental procedures involving manipulation of gingival tissue, the periapical region of teeth, or perforation of oral mucosa.

High-risk cardiac conditions include:

1.      Prosthetic cardiac valves, including transcatheter prostheses, or prosthetic material used for cardiac valve repair

2.      Previous infective endocarditis

3.      Unrepaired cyanotic congenital heart disease

4.      Repaired congenital heart disease with a residual shunt or valvular regurgitation at or adjacent to a prosthetic patch or prosthetic device

5.      Cardiac transplant recipients with valve regurgitation attributable to a structurally abnormal valve

A commonly recommended adult regimen is:

Amoxicillin 2 g orally 30 to 60 minutes before the qualifying dental procedure.

Routine antibiotic prophylaxis is not recommended for the general population.

14. Complications

Cardiac

1.      Valve destruction

2.      Severe regurgitation

3.      Heart failure

4.      Perivalvular abscess

5.      Conduction abnormalities

Embolic and Metastatic

1.      Septic pulmonary emboli in right-sided IE

2.      Stroke in left-sided IE

3.      Splenic or renal infarction in left-sided IE

4.      Metastatic abscesses

5.      Mycotic aneurysm

Renal

1.      Immune complex glomerulonephritis

2.      Acute kidney injury

Systemic

1.      Sepsis

2.      Septic shock

3.      Persistent bacteremia

15. Prognosis

Prognosis depends on:

1.      Causative organism

2.      Valve involved

3.      Presence of prosthetic material

4.      Heart failure

5.      Persistent bacteremia

6.      Embolic complications

7.      Renal dysfunction

8.      Perivalvular extension

9.      Timeliness of appropriate therapy

Isolated right-sided IE generally has a better prognosis than complicated left-sided IE, but S. aureus infection, persistent bacteremia, large vegetations, recurrent pulmonary emboli, respiratory failure, and concomitant left-sided disease indicate a higher-risk course.

16. Key Clinical Insight

Fever + injection drug use + tricuspid regurgitation murmur that increases with inspiration + S. aureus bacteremia + septic pulmonary emboli strongly suggests right-sided tricuspid infective endocarditis.

In this patient:

S. aureus bacteremia + tricuspid vegetation + septic pulmonary emboli = acute right-sided infective endocarditis complicated by septic pulmonary embolization.

References

1.      DeSimone DC, Marks L, Dayer MJ, et al. Infective Endocarditis: Diagnosis, Antibiotic Therapy, and Management: A Scientific Statement From the American Heart Association. Circulation. Published online September 8, 2026. doi:10.1161/CIR.0000000000001466.

2.      Delgado V, Ajmone Marsan N, de Waha S, et al. 2023 ESC Guidelines for the management of endocarditis. Eur Heart J. 2023;44(39):3948-4042. doi:10.1093/eurheartj/ehad193.

3.      Fowler VG Jr, Durack DT, Selton-Suty C, et al. The 2023 Duke-International Society for Cardiovascular Infectious Diseases Criteria for Infective Endocarditis: Updating the Modified Duke Criteria. Clin Infect Dis. 2023;77(4):518-526. doi:10.1093/cid/ciad271.