What is the approach to assessing a patient for suspected endocarditis, considering their medical history, risk factors, and potential need for empiric antibiotic therapy and surgical intervention?

Assessment of Suspected Infective Endocarditis

At the first clinical suspicion of infective endocarditis, immediately obtain at least 3 sets of blood cultures from separate sites before initiating any antibiotics, followed by transthoracic echocardiography (TTE) as the initial imaging modality. 1

Initial Clinical Evaluation

Key Historical Features to Identify

• Fever is present in up to 90% of patients and represents the cardinal symptom, often accompanied by chills, poor appetite, and weight loss 1, 2
• Risk factors requiring specific inquiry include:
  • Prosthetic cardiac valves or implantable cardiac devices 1
  • Intravenous drug use (increasingly common cause of right-sided endocarditis) 1, 2
  • Recent invasive procedures or dental work 2, 3
  • Indwelling IV catheters or frequent healthcare contact 1, 4
  • Pre-existing structural heart disease or congenital heart disease 1, 4

Physical Examination Findings

• New or changing heart murmur occurs in up to 85% of patients, most commonly due to valvular insufficiency 1, 2
• Embolic phenomena are present in up to 25% of patients at diagnosis 1, 2
• Classic peripheral stigmata include splinter hemorrhages, Roth spots (retinal hemorrhages with pale centers), Osler's nodes, Janeway lesions, and splenomegaly 1, 2
• Signs of heart failure including evidence of valvular dysfunction 1

Microbiological Assessment

Blood Culture Protocol

• Obtain at least 3 sets of blood cultures from separate venipuncture sites at 30-minute intervals before starting any antimicrobial therapy 1, 5
• Blood cultures may be negative in the setting of prior antibiotic use, making early collection critical 1
• Persistently positive blood cultures in association with characteristic symptoms and physical findings support the diagnosis 1
• Repeat blood cultures should document clearance of bacteremia within 48-72 hours of appropriate therapy for most organisms 6

When Blood Cultures Are Negative

• Consider directed serological testing for Q fever and Bartonella 7
• Molecular diagnostics (16S rRNA gene PCR/sequencing) may be applied to resected valves 7, 8

Echocardiographic Assessment Algorithm

Step 1: Transthoracic Echocardiography (TTE)

• TTE is recommended as the first-line imaging modality in all suspected IE cases 1
• TTE has 70% sensitivity for vegetations on native valves and 50% for prosthetic valves 1
• TTE is adequate for isolated right-sided native valve IE with good quality examination and unequivocal findings 1

Step 2: Transesophageal Echocardiography (TEE)

TEE is mandatory in the following situations:

• All patients with prosthetic heart valves or intracardiac devices 1
• Negative or non-diagnostic TTE when clinical suspicion remains high 1
• To detect complications including abscesses, perforations, pseudoaneurysms, and fistulas 1
• TEE has >95% sensitivity for detecting vegetations compared to 60-75% for TTE 1, 2
• TEE is superior to TTE for visualizing paravalvular abscesses, particularly in prosthetic valve endocarditis 1

Step 3: Repeat Imaging

• Repeat TTE and/or TEE within 5-7 days if initial examination is negative but clinical suspicion remains high 1
• Immediate repeat echocardiography is indicated for new murmur, embolism, persistent fever, heart failure, abscess, or atrioventricular block 1

Advanced Imaging Modalities

CT Heart Function and Morphology

• CT is superior to echocardiography for detecting and visualizing the full extent of paravalvular abscess, pseudoaneurysm, or fistula, particularly in prosthetic valve patients 1
• CT has 100% sensitivity, specificity, PPV, and NPV for vegetations >1 cm in size 1
• CT may be equivalent or superior to echocardiography for identifying vegetations and valve dehiscence in prosthetic valve endocarditis 1

CT Chest

• Primary role is evaluating pulmonary complications in right-sided endocarditis, demonstrating septic pulmonary infarcts and abscesses 1

Nuclear Imaging (FDG-PET/CT)

• Proven role in diagnosis of cardiovascular electronic implanted device infections 1
• Useful for detecting embolic events when TTE/TOE findings are negative or doubtful 1

Laboratory Assessment

• Elevated inflammatory markers including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) 1
• Leucocytosis and anemia are common 1
• Microscopic hematuria may indicate glomerulonephritis 1, 2

Critical Decision Points for Empiric Antibiotics

When to Withhold Antibiotics

• Avoid empirical antimicrobial therapy for undefined febrile illness unless the patient's clinical condition (sepsis) warrants empirical therapy 1, 5
• Administering empiric antibiotics without blood cultures leads to culture-negative endocarditis, making diagnosis and treatment more difficult 5

When to Initiate Empiric Therapy

Start empiric antibiotics immediately after obtaining blood cultures in:

• Severe sepsis or septic shock 5
• Acute heart failure due to severe valve destruction 1, 5
• Severe systemic signs of infection 5

Empiric Antibiotic Regimens

For native valve, community-acquired infection:

• Ampicillin 12 g/day IV in 4-6 doses + flucloxacillin/oxacillin + gentamicin 3 mg/kg/day IV or IM in single dose 5
• For penicillin allergy: Vancomycin 30-60 mg/kg/day IV in 2-3 doses + gentamicin 3 mg/kg/day 5

For prosthetic valve or healthcare-associated infection:

• Vancomycin 30 mg/kg/day IV in 2 doses + gentamicin 3 mg/kg/day + rifampin 900-1200 mg IV or oral in 2-3 divided doses 5, 9

Risk Stratification and Prognostic Assessment

High-Risk Features Requiring Early Surgical Referral

• Heart failure, periannular complications, and/or S. aureus infection carry the highest risk of death and need for surgery 1
• When all three factors are present, risk reaches 79% 1
• Persistent bacteremia 48-72 hours after appropriate antibiotics indicates lack of infection control and is an independent risk factor for mortality 1

Additional Poor Prognostic Indicators

• High degree of comorbidity, diabetes, septic shock 1
• Moderate-to-severe ischemic stroke or brain hemorrhage 1
• Need for hemodialysis 1

Multidisciplinary Team Involvement

• Early involvement of cardiology and infectious disease specialists is highly recommended at the first suspicion of IE 1, 2, 5
• Surgical consultation should be considered early in cases with risk factors for complications, as approximately 50% of patients will require surgical intervention 5
• Patients with complicated IE should be referred to a reference center with surgical facilities and an Endocarditis Team 1

Common Pitfalls to Avoid

• Do not start antibiotics before obtaining blood cultures unless the patient is in septic shock or has acute heart failure 1, 5
• Do not rely solely on TTE in patients with prosthetic valves or intracardiac devices—TEE is mandatory 1
• Do not dismiss the diagnosis with a single negative echocardiogram when clinical suspicion remains high—repeat imaging within 5-7 days 1
• Do not overlook S. aureus bacteremia—echocardiography is justified in all cases given the frequency and virulence of IE in this setting 1