What is the best treatment approach for endocarditis?

Treatment of Infective Endocarditis

The optimal treatment of infective endocarditis requires a combined approach of prolonged antimicrobial therapy tailored to the causative organism plus urgent cardiac surgery for specific high-risk complications including heart failure, uncontrolled infection, and prevention of embolism. 1

Multidisciplinary Team Management

• Patients with complicated IE must be evaluated and managed at a reference center with immediate surgical facilities and a multidisciplinary Endocarditis Team including an infectious disease specialist, microbiologist, cardiologist, imaging specialists, and cardiac surgeon. 1
• Even non-complicated IE cases managed at non-reference centers require early and regular communication with the reference center. 1

Antimicrobial Therapy

General Principles

• Draw three sets of blood cultures at 30-minute intervals before initiating antibiotics, then start treatment promptly. 1
• Prolonged therapy is essential: Native valve endocarditis (NVE) requires 2-6 weeks, while prosthetic valve endocarditis (PVE) requires at least 6 weeks due to bacterial tolerance in biofilms. 1
• Bactericidal drug combinations are preferred over monotherapy, particularly for tolerant organisms. 1

Organism-Specific Treatment

Penicillin-susceptible streptococci (MIC ≤0.125 mg/L):

• Penicillin G or ceftriaxone for 4 weeks achieves >95% cure rate. 1
• Short-term 2-week therapy is acceptable when combining penicillin or ceftriaxone with gentamicin or netilmicin in uncomplicated cases. 1
• Ceftriaxone plus gentamicin given once daily is particularly convenient for outpatient therapy. 1

Enterococcal endocarditis:

• Ampicillin is indicated for septicemia and endocarditis caused by susceptible Gram-positive organisms including enterococci. 2
• The addition of an aminoglycoside enhances effectiveness when treating streptococcal and enterococcal endocarditis. 2, 3
• Treatment duration should be 4-6 weeks with combination therapy. 4

Staphylococcal endocarditis:

• Nafcillin or oxacillin (or cephalosporins like cefazolin) for 4-6 weeks for Staphylococcus aureus. 4
• For staphylococcal PVE, include rifampin whenever the strain is susceptible. 1

HACEK organisms:

• Ceftriaxone 2 g/day is the standard treatment: 4 weeks for NVE and 6 weeks for PVE. 1
• Ampicillin is no longer first-line due to beta-lactamase production. 1

Non-HACEK Gram-negative bacteria:

• Early surgery plus long-term therapy (at least 6 weeks) with bactericidal combinations of beta-lactams and aminoglycosides is recommended. 1
• Consider adding quinolones or cotrimoxazole. 1

Fungal endocarditis:

• Mortality exceeds 50%, and treatment necessitates combined antifungal administration and surgical valve replacement. 1

Blood culture-negative endocarditis:

• Consultation with an infectious disease specialist is recommended. 1
• Specific regimens exist for Brucella, Coxiella burnetii (Q fever), Bartonella, and other rare pathogens. 1

Empirical Therapy Considerations

The initial choice depends on:

• Previous antibiotic exposure
• Native valve versus prosthesis (and timing of surgery for PVE)
• Location of infection acquisition (community, nosocomial, or healthcare-associated)
• Local epidemiology and antibiotic resistance patterns 1

For urgent empirical therapy before organism identification: Combine aqueous penicillin G, nafcillin, and gentamicin. 4

Surgical Indications and Timing

Urgent Surgery (Within Days)

Heart failure indications:

• Aortic or mitral NVE or PVE with severe regurgitation or obstruction causing symptoms of heart failure or echocardiographic signs of poor hemodynamic tolerance must be treated by urgent surgery. 1

Uncontrolled infection indications:

• Locally uncontrolled infection (abscess, false aneurysm, fistula, enlarging vegetation) must be treated by urgent surgery. 1
• Infection caused by fungi or multiresistant organisms must be treated by urgent surgery. 1
• Persisting positive blood cultures despite appropriate antibiotic therapy warrants urgent surgery. 1

Prevention of embolism indications:

• Aortic or mitral NVE or PVE with persistent vegetations >10 mm after ≥1 embolic episodes despite appropriate antibiotic therapy must be treated by urgent surgery. 1

Emergency Surgery (Within Hours)

• Aortic or mitral NVE or PVE with severe acute regurgitation, obstruction or fistula causing refractory pulmonary edema or cardiogenic shock requires emergency surgery. 1

Timing Considerations for Neurological Complications

• After silent embolism or transient ischemic attack, cardiac surgery should proceed without delay if indicated. 1
• Following intracranial hemorrhage, surgery should generally be postponed for ≥1 month. 1
• Neurosurgery or endovascular therapy are indicated for very large, enlarging or ruptured intracranial infectious aneurysms. 1

Device-Related Infective Endocarditis

• Prolonged antibiotic therapy (before and after extraction) and complete hardware removal (device and leads) are recommended in definite cardiac device-related IE and isolated pocket infection. 1
• Percutaneous extraction is recommended in most patients, even those with vegetations >10 mm. 1
• After device extraction, reassess the need for reimplantation. 1

Diagnostic Approach

• TTE is the first-line imaging modality in suspected IE. 1
• TOE is recommended in all patients with clinical suspicion of IE and negative or non-diagnostic TTE, and when prosthetic heart valve or intracardiac device is present. 1
• Repeat TTE and/or TOE within 5-7 days if initially negative when clinical suspicion remains high. 1
• Intra-operative echocardiography is recommended in all cases requiring surgery. 1

Outpatient Parenteral Antibiotic Therapy (OPAT)

Critical phase (weeks 0-2):

• Complications occur most frequently during this phase; inpatient treatment is preferred. 1
• Consider OPAT only for oral streptococci or Streptococcus bovis on native valve in stable patients without complications. 1

Continuation phase (beyond week 2):

• Consider OPAT if medically stable. 1
• Do not consider OPAT if heart failure, concerning echocardiographic features, neurological signs, or renal impairment present. 1
• Requires patient education, daily nursing evaluation, and physician assessment 1-2 times weekly. 1

Common Pitfalls

• Complications develop in the majority of patients: 57% experience one complication, 26% experience two, and 14% experience three or more. 5
• Periannular abscesses occur in 42-85% of cases and are associated with higher morbidity and mortality. 5
• Systemic embolization occurs in 22-50% of cases, most commonly affecting the central nervous system. 5
• The duration of antibiotic treatment is based on the first day of effective therapy, not the day of surgery. 1
• After surgery during antibiotic therapy, continue the NVE regimen (not PVE regimen) unless valve cultures are positive. 1