Overview

Infective endocarditis (IE) involves the inflammation of the inner lining of the heart as well as the valves.

It shows a predilection for males (2:1) and preferentially affects individuals older than 65 years. This is thought to be due to the increased prevalence of risk factors in this age group.

• Risk factors for community-acquired infection
  • Immunosuppressive states, especially diabetes mellitus
  • IV drug use
    • S.aureus is a common organism and shows a predilection for healthy, native tricuspid valves
    • S. epidermis is a common organism
  • Poor dentition
    • Viridans streptococci are common causes
  • Degenerative valve disease, such as calcific aortic stenosis or mitral valve prolapse
  • Congenital heart defects, such as ventricular septal defects
• Risk factors for hospital-acquired infection
  • Recent prosthetic valve placement
  • Recent vascular catheterisation
  • Hemodialysis
  • Recent hospitalisation
  • Recent extra-cardiac operative procedures

Etiology

Common organisms include:

• Bacterial
  • Staphylococci
    • S. aureus – Most common cause of IE
    • Seen in the setting of skin infections, abscesses, vascular access sites such as intravenous and central lines, or from intravenous drug use.
    • S. epidermis is commonly seen to affect native and prosthetic heart valves and is associated with a history of wound infection
    • S. lugdenensis causes a rapidly destructive acute endocarditis that is associated with previously normal valves and multiple emboli.
  • Streptococci
    • S. pneumoniae
    • S. progenies
    • Viridans streptococci such as S.mitis and S.sanguinis
    • S.gallolyticus – associated with colon carcinoma
  • Enterococci
    • E. faecalis
    • E. faecium
  • HACEK
    • Made up of Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, and Kingella
  • Coxiella brunette (Q fever)
    • Associated with a history of contact with farm animals. The aortic valve is usually affected, and there may also be hepatitis, pneumonia, and purpura.
  • Brucella
    • Brucella **endocarditis is associated with a history of contact with goats or cattle and often affects the aortic valve.
• Fungal
  • Occurs in 1% of cases
  • Commonly seen in immunocompromised individuals
  • Caused by Candida and Aspergillus species

Pathophysiology

Healthy, intact endocardium is impervious to bacterial seeding; however, infection by highly aggressive strains such as Staph. aureus may cause endocarditis in a previously normal heart.

The customary sequence of development of IE requires 2 conditions:

• Injured endocardium
• Period of bacteremia

Endocardial injury can occur in many ways:

• High turbulence flow around diseased valves
• Direct mechanical trauma caused by catheter or electrode insertion
• In intravenous drug use, repetitive valvular barrage by co-injected particulate matter

Injured endocardium becomes more prone to bacterial seeding because the damaged area attracts increased deposits of platelets and fibrin. These deposits create a vulnerable site for colonization by blood-borne bacteria, leading to the formation of a sterile, non-bacterial thrombotic vegetation.

This collection of platelets and fibrin not only provides a surface for bacterial attachment but also shields proliferating bacteria from the host’s immune defenses, facilitating their growth and survival

Following a transient period of bacteremia, seeding occurs, and adjacent tissues are destroyed, while abscesses may form.

Extra cardiac manifestations, such as vasculitis and skin lesions, may occur as a result of either emboli or immune complex deposition. Distant embolisation may cause infarction of the spleen and kidneys.

Clinical Presentation

History

Ask about the above-mentioned risk factors.

• Subacute endocarditis
  • Is an indolent process that occurs in the setting of preexisting congenital or valvular heart disease.
  • Presents with:
    • Persistent fever and chills
    • Generalised body weakness
    • Night sweats
    • Unintentional weight loss
    • Features of congestive heart failure, such as dyspnea, orthopnea, PND, and lower limb edema
    • Joint pain
• Acute endocarditis
  • Aggressive; complications arise in a week
  • Most predominate type, as there is a rise in invasive intracardiac procedures and recreational drug use
  • Presents with:
    • Rapid onset of high-grade fever and chills
    • Rapid onset of features of heart failure – dyspnea and fatigue
    • Neuropsychiatric symptoms due to CNS involvement
• Post-operative endocarditis
  • This may present as an unexplained fever in a patient who has had heart valve surgery.
  • Divided into:
    • Early – occurs within 60 days of surgery (coagulase-negative staphylococcus most probable cause)
    • Late – occurs after 60 days of surgery
  • May resemble acute or subacute endocarditis
• Features unique to endocarditis seen in IV drug users
  • Present with pleuropulmonary symptoms such as:
    • Dyspnea
    • Cough
    • Chest pain
  • As mentioned above, there is a predilection for the native tricuspid valve in this population involving the pulmonary vasculature by showering septic emboli into the system
• Factors that may cause an atypical presentation
  • Immunosuppression
  • Old age
  • Anti-pyretic use
  • Previous antibiotic courses

Physical examination

• General examination
  • Fever
  • Pallor
  • Tachypnea
  • Tachycardia
  • Hypotension – if developing cariogenic or septic shock
  • Petechiae
  • Lower limb edema – in the setting of heart failure

Systemic examination

• Cardiovascular examination
  • Splinter haemorrhages
    • Dark red linear lesions in the nailbeds
    • Hemorrhages that do not extend for the entire length of the nail are more likely to be the result of infection rather than trauma.
  • Osler nodes
    • Tender subcutaneous nodules are usually found on the distal pads of the digits
  • Janeway lesions
    • Non-tender maculae on the palms and soles
  • Finger clubbing
  • Distended neck vein – in the setting of heart failure
  • Heart murmurs (present in 85% of cases)
• Per abdomen
  • Splenomegaly
  • Localized peritonitis – suggests bowel perforation from mesenteric arterial occlusion
• Ophthalmological examination
  • Roth’s spots
    • Retinal hemorrhages with pale centers
• CNS examination
  • Focal motor or sensory deficits that correspond to the impacted vascular territories
  • Signs of meningeal irritation
    • Stiff neck
    • Positive Kernig and Brudzinski signs

Signs of systemic septic emboli result from left heart disease and are more commonly associated with mitral valve vegetations. Multiple embolic pulmonary infections or infarctions are due to right heart disease.

Evaluation

• Blood and urine studies
  • Complete blood count
    • Normocytic anemia – common in subacute IE
    • Leukocytosis – seen in acute IE
  • ESR and CRP – elevated
  • UECs
    • Proteinuria
    • Microscopic hematuria
    • Deranged electrolytes
  • Rheumatoid factor – positive
  • Blood culture – helps determine:
    • Type of organism
    • Antibiotic choice
    • Degree of severity
    • Source of infection
• Imaging studies
  • Echocardiography – indirect diagnostic method of choice. Helps:
    • Visualise abscesses
    • Predict potential complications (especially those embolic in nature) by assessing:
      • Size of emboliNumber of emboliMobility of emboliProlapsing or non-prolapsingCalcified or not
      Large, multiple, mobile, or pedunculated, prolapsing, non-calcified vegetations are at an increased risk of embolic events.
  • Chest x-ray
    • Pulmonic embolic phenomena
    • Pleural effusion
    • Pulmonary abscesses
    • Cardiomegaly – in the setting of heart failure
  • Electrocardigram
    • Typically normal, however, in advanced cases, may show:
      • First-degree AV block
      • Interventricular conduction delays
    • Positive findings are associated with a poor prognosis
• Modified Duke Criteria 2023
  • Diagnosis requires satisfaction of either two major criteria, one major and three minor criteria, or five minor criteria
  Major Criteria
  • Positive blood culture
    • Typical organism from two cultures
    • Persistent positive blood cultures taken > 12 hrs apart
    • Three or more positive cultures taken over > 1 hr
  • Endocardial involvement
    • Positive echocardiographic findings of vegetations
    • New valvular regurgitation
  Minor Criteria
  • Predisposing conditions such as underlying valvular abnormalities, structural heart disease, or intravenous drug use.
  • Fever is defined by a temperature greater than 38 degrees Celsius.
  • Evidence of vascular phenomena such as mycotic aneurysms, intracranial hemorrhage, Janeway lesions, major arterial emboli, or septic pulmonary infarcts.
  • Evidence of immunologic phenomena such as Osler’s nodes, Roth spots, glomerulonephritis, or positive rheumatoid factor.
  • Positive blood cultures that do not satisfy the aforementioned major criterion or serologic evidence of infection consistent with infectious endocarditis

Treatment

Prevention

• Maintaining good oral hygiene
• Antibiotic prophylaxis
  • Indications for antibiotic prophylaxis
    • High-risk cardiac conditions – should receive prophylaxis when undergoing dental procedures and invasive respiratory tract procedures that involve incision or biopsy of the respiratory mucosa
      • Prosthetic cardiac valve
      • Cardiac transplant recipients with cardiac valvular disease
      • Cyanotic congenital heart disease
      • Congenital heart disease with a high-pressure gradient lesion
    • In patients undergoing percutaneous implantation of a prosthetic valve, pacemaker, or implantable cardiodefibrillator
  • Antibiotic choice and dosing. All doses shown below are administered once as a single dose 30-60 min before the procedure:
    • Standard general prophylaxis: Amoxicillin 2 g PO
    • Unable to take oral medication: Ampicillin 2 g IV/IM or cefazolin/ceftriaxone 1 g IM or IV
    • Allergic to penicillin: Cephalexin 2 g PO or other first- or second-generation oral cephalosporin in equivalent dose
    • Allergic to penicillin: Azithromycin or clarithromycin: 500 mg PO
    • Allergic to penicillin: Doxycycline 100 mg

Antibiotic treatment

Antibiotic treatment duration and selection depend on the nature of the valve involved and the resistance pattern of the infecting organism.

• Native valve endocarditis with penicillin-susceptible viridans group strep or S. gallolyticus
  • Ceftriaxone 2 gm IV every 24 hours plus gentamicin 3 mg/kg IV every 24 hours for 2 weeks OR
  • Ceftriaxone 2 gm every 24 hours IV for four weeks OR
  • Aqueous penicillin G 12 to 18 million units every 24 hours via continuous IV drip or in 4 to 6 equally divided doses
• Prosthetic valve endocarditis with penicillin-susceptible viridans group strep or S. gallolyticus
  • 24 million units of penicillin G every 24 hours for 6 weeks OR
  • Ceftriaxone 2 gm with or without gentamicin 3 mg/kg every 24 hours every 6 weeks
• Native valve methicillin-sensitive S. aureus (MSSA) endocarditis
  • Nafcillin 2 gm every four hours for 6 weeks OR
  • Cefazolin 2 gm every 8 hours for 6 weeks
  Prosthetic valve MSSA disease should receive gentamicin 3 mg/kg IV in 2 to 3 divided doses plus rifampin 900 mg IV in 2 to 3 equally divided doses every 24 hours for 2-weeks and 6-weeks, respectively, in addition to the above-described nafcillin regimen
• Native  methicillin-resistant S. aureus (MRSA) endocarditis
  • Vancomycin 15mg/kg every 12 hours for 6 weeks ORDaptomycin 8 mg/kg daily for 6 weeks
  Prosthetic valve MRSA disease should receive gentamicin 3 mg/kg IV in 2 to 3 divided doses plus rifampin 900 mg IV in 2 to 3 equally divided doses every 24 hours for 2-weeks and 6-weeks, respectively, in addition to the above-described regimen
• Native and prosthetic valve enterococcal infections
  • Ampicillin or penicillin G plus an aminoglycoside such as gentamicin for 4 to 6 weeks

Surgical treatment

Cardiac surgery with debridement of infected material and valve replacement may be required in a substantial proportion of patients, particularly those with Staph. aureus and fungal infections

• Indications
  • Heart failure due to valve damage and refractory to standard medical therapy
  • Failure of antibiotic therapy (persistent/uncontrolled infection) after 72 hours of appropriate antibiotic treatment
  • Large vegetations on left-sided heart valves with an echo appearance suggesting high risk of emboli
  • Previous evidence of systemic emboli
  • Abscess formation
  • Fungal IE (except that caused by Histoplasma capsulatum)
  • Conduction disturbances caused by a septal abscess

Complications

• Intra-cardiac complications
  • Myocardial infarction
  • Pericarditis
  • Cardiac arrhythmia
  • Cardiac valvular insufficiency
  • Congestive heart failure
    • The most common intracardiac complication of subacute endocarditis
    • Caused by aortic valve insufficiency
  • Sinus of Valsalva aneurysm
  • Aortic root or myocardial abscesses
• Peripheral complications secondary to embolisation
  • Arthritis
  • Myositis
  • Mycotic aneurysms
  • Glomerulonephritis
  • Acute renal failure
  • Stroke syndromes
  • Mesenteric or splenic abscess or infarct