What is infective endocarditis and how is it treated?

Infective Endocarditis: Definition and Treatment

Infective endocarditis is a fatal disease if untreated, requiring immediate echocardiography when suspected, prolonged antimicrobial therapy tailored to the causative organism, and close collaboration between cardiologists, microbiologists, and cardiac surgeons, with approximately 50% of patients requiring surgical intervention for complications. 1

What is Infective Endocarditis?

IE is an endovascular, microbial infection of intracardiac structures facing the blood, including infections of large intrathoracic vessels and intracardiac foreign bodies. 1

• The characteristic early lesion is a variably sized vegetation, though destruction, ulceration, or abscess formation may appear earlier on echocardiography 1
• Despite advances in medical, surgical, and critical care interventions, IE remains associated with considerable morbidity and mortality 1
• The disease has evolved with an aging population and increasing use of implantable cardiac devices and prosthetic valves 2

Critical Diagnostic Approach

IE must be considered early in every patient with fever or septicemia and cardiac murmurs, with echocardiography applied without delay. 1

Blood Cultures

• Obtain at least 3 sets of blood cultures from separate sites before initiating antibiotic therapy 1
• This is particularly critical in IV drug users with any systemic infection, as they have significant risk of endocarditis 3

Echocardiography Strategy

• Transthoracic echocardiography (TTE) should be performed initially when IE is suspected 1
• Transesophageal echocardiography should follow if clinical suspicion remains high despite negative TTE 1
• Obtain TTE before completing antimicrobial therapy to establish a new baseline for subsequent comparison 1

Antimicrobial Treatment

Treatment requires prolonged antimicrobial therapy (typically 4-6 weeks) based on the causative organism and susceptibility patterns. 1, 4

Streptococcal Endocarditis

• Penicillin-sensitive viridans or non-enterococcal group D streptococcal endocarditis: aqueous penicillin G alone for 4 weeks OR combined penicillin and streptomycin for 2 weeks 4
• Enterococcal endocarditis: combination of aqueous penicillin G with either streptomycin or gentamicin for 4-6 weeks 4

Staphylococcal Endocarditis

For oxacillin-susceptible S. aureus (OSSA) right-sided endocarditis without complications, parenteral β-lactam therapy (with or without aminoglycoside) for 2 weeks is adequate. 1

• Uncomplicated right-sided S. aureus endocarditis in IV drug users: 2-week regimen of nafcillin plus gentamicin has proven effective 1
• Left-sided or complicated S. aureus endocarditis: semisynthetic penicillin (nafcillin or oxacillin) or cephalosporin (cephalothin or cefazolin) for 4-6 weeks 4
• Oxacillin-resistant S. aureus (ORSA): glycopeptide therapy often requires more prolonged treatment regimens and may be less effective due to limited bactericidal activity and poor vegetation penetration 1

Pneumococcal Endocarditis

• High-dose penicillin or third-generation cephalosporin for penicillin-resistant strains without meningitis 1
• With meningitis: high doses of cefotaxime; if resistant (MIC ≥2 μg/mL), add vancomycin and rifampin 1
• Coordinate treatment with an infectious diseases specialist due to evolving resistance patterns 1

Coagulase-Negative Staphylococci

• S. lugdunensis causes substantially more virulent IE with high rates of perivalvular extension and metastatic infection, requiring careful monitoring despite uniform antibiotic susceptibility 1

Brucella Endocarditis

• Aggressive combination therapy: doxycycline 200 mg/24 hours, rifampin 300-600 mg/24 hours, cotrimoxazole 960 mg/12 hours, plus streptomycin for at least 3-6 months 5
• Treatment success defined as antibody titer falling below 1:60 5

Empiric Therapy

• When urgent treatment is necessary before organism identification: combination of aqueous penicillin G, nafcillin, and gentamicin 4

Surgical Indications

Approximately 50% of endocarditis patients require surgical intervention, making early surgical consultation essential. 5

Class I Indications for Surgery

• Heart failure due to valve dysfunction 5
• Uncontrolled infection with abscess formation 5
• Persistent positive blood cultures despite appropriate antimicrobial therapy 5
• Prevention of systemic embolism (particularly with large vegetations) 5

Timing Considerations

• The period of greatest risk for systemic emboli is within the first 1-2 weeks, making early detection and intervention critical 3
• Early surgical intervention is increasingly advocated when complications develop 6

Multidisciplinary Team Approach

Close cooperation between cardiologists, microbiologists, and cardiac surgeons is mandatory when IE is suspected or definite. 1

• All cases should be discussed by an Endocarditis Team including infectious disease specialists, cardiologists, cardiac surgeons, and microbiologists 5
• Consultation with infectious disease specialists is mandatory for rare presentations like Brucella endocarditis 5

Outpatient Parenteral Antibiotic Therapy (OPAT)

OPAT may be considered for select patients after initial stabilization, but requires strict criteria and is problematic in IV drug users. 1

Essential OPAT Criteria

• Reliable support system at home with easy hospital access for prompt reevaluation 1
• Regular home infusion nurse visits to monitor for complications, treatment failure, or IV access problems 1
• Weekly physician visits to assess clinical status 1

OPAT Contraindications

• IV drug users have compliance difficulties and high risk of IV access misuse, making OPAT problematic in this population 1, 3

Monitoring During Treatment

Short-Term Follow-Up

• Monitor for developing or worsening congestive heart failure 1
• Assess for delayed aminoglycoside toxicity (audiological and vestibular) despite maintaining appropriate drug concentrations during therapy 1
• Serial audiograms should be performed during therapy 1
• Obtain at least 3 sets of blood cultures from separate sites for any febrile illness before initiating antibiotics 1

Long-Term Follow-Up

• Evaluation of valvular and ventricular function with echocardiography 1
• Scrupulous oral hygiene and frequent professional dental visits 1

Prevention

Antibiotic prophylaxis should be given before bacteremia is expected in high-risk patients. 1

High-Risk Patients Requiring Prophylaxis

• Previous history of IE 1
• Presence of prosthetic heart valves or other foreign material 1
• Surgically created conduits 1
• Complex cyanotic congenital abnormalities 1

Timing

• If prophylaxis is not given prior to the bacteremia-inducing event, intravenous antibiotics may help with late clearance if administered within 2-3 hours 1

Critical Pitfalls to Avoid

• Never delay echocardiography when IE is suspected—delayed diagnosis or postponed therapeutic measures result in high mortality 1
• Do not discharge IV drug users with systemic symptoms without blood cultures and endocarditis assessment—missing endocarditis can be fatal 3
• Avoid relying solely on antibiotics without adequate surgical drainage for associated abscesses—this is insufficient treatment 3
• Do not use trimethoprim alone for Brucella endocarditis—cotrimoxazole (containing both trimethoprim and sulfamethoxazole) is required 5
• Ensure adequate treatment duration (minimum 3-6 months for Brucella)—shorter courses are associated with treatment failure 5
• Do not use glycopeptide-based short-course regimens for right-sided S. aureus IE—these are less effective than β-lactam therapy 1
• Never remove IV catheters before completion of antimicrobial therapy—prompt removal is required only at treatment completion 1

Patient Education

• Educate regarding signs of endocarditis and need for antibiotic prophylaxis for certain dental/surgical/invasive procedures 1
• Provide drug rehabilitation referral for patients who use illicit injection drugs 1, 3
• Thorough dental evaluation and treatment should be performed if not done earlier 1