Infective Endocarditis: Background, Pathophysiology, Symptoms, Diagnosis, Treatment and Prophylaxis

Definition

Infective endocarditis is an inflammation of the endocardium (a thin connective tissue layer that lines the heart along with the valves ), which is caused by pathogens such as bacteria or fungi and despite the optimal therapy it's associated with a high mortality rate (20-30%).

Epidemiology

The latest incidence of IE is approximately   ( 2 to 5  cases per 100,000 inhabitants annually). Men are affected about twice as often. Although rarely are the patients younger than 60 years.

Classification

Depending on the course

• The foudroyant acute septic endocarditis
• subacute endocarditis (endocarditis lenta)

Depending on valves

• Native valves endocarditis
• Prosthetic valves endocarditis : If the endocarditis occurs within one year after a valve replacement, one speaks of early prosthetic valve endocarditis, then of a late prosthetic valve endocarditis.

Also 

• Significantly more frequent left ventricular endocarditis involving the mitral or aortic valve
• prognostically it's better classified when right-sided endocarditis (Risk Factor: i.v.-Drug Abuse, central venous catheter) which is usually associated with the invasion of the tricuspid valve

Pathogenesis

In the area of ​​endocardial lesions, which occur in particular on mechanically stressed structures (especially those affected by the mitral and aortic valve), the deposition of sterile thrombotic vegetation forms an ideal ground for pathogens. In the case of transient bacteremia (eg iatrogenic or in infectious diseases) colonization of the initially germ-free thrombotic deposition with permanent bacteremia is possible.

Symptoms

1. General: fever, chills,  fatigue, paleness, tachycardia

2. Cardiac:

• heart murmur or aggravation of a pre-existing heart murmur
• Heart failure (valve insufficiency(
• Valve perforation and rupture with acute decompensation (pulmonary edema(

3. Extracardially

I. Central nervous system

• Septic-embolic encephalitis (often multiple ischemia(
• Septic sinus vein thrombosis
• Mycotic aneurysms with risk of subarachnoid hemorrhage

II. Cutaneous

• Petechiae
• Janeway Lesions: Painless hemorrhages on palms and soles

Janeway Lesions

• Osler nodules: painful, nodular bleeding on fingers and toes, embolic or in immune complex vasculitis

Osler nodules

• Splinter hemorrhages: bleeding in the nail bed as a result of immune complex deposits or micro thrombosis; esp. in subacute forms

Splinter hemorrhages

III. Kidney

• kidney infarcts
• Focal or diffuse immune complex glomerulonephritis

IV. Spleen

Spleen enlargement and septic embolisms in the spleen

V. Eyes

• Retinal embolism and conjunctival hemorrhage
• Roth's spots (retinal bleeding(

Roths spots (retinal bleeding)

Pathogen

• Staphylococcus aureus (45-65%): most common causative agent of endocarditis acuta
• Streptococcus viridans (30%): most common causative agent of endocarditis lenta
• Staphylococcus epidermidis: most common germ transmitted via infected venous indwelling catheters
• Enterococcus faecalis (<10%): Multiple antibiotic resistance: Always resistance on penicillin G and cephalosporins
• Streptococcus bovis: detection of Streptococcus bovis must be thought of as colon carcinoma; accordingly, a colonoscopy is mandatory in the course
• HACEK group: group of gram-negative pathogens from the mouth and throat, responsible for about 3%.

1. H - Haemophilus aphrophilus and Haemophilus paraphrophilus
2. A - Aggregatibacter actinomycetemcomitans (formerly Actinobacillus actinomycetemcomitans)
3. C - Cardiobacterium hominis
4. E - Eikenella corrodens
5. K - Kingella kingae

• Fungi (Aspergillus, Candida): in immunosuppression (e.g., HIV, renal transplant state(

Diagnosis

Blood cultures for pathogen detection

• blood collection before the start of antibiotic therapy (continuous bacteremia(
• at least 3-5 separate blood culture couples
• the collected blood must be transported  to the laboratory within 2 hours
• Antibiogram to detect possible resistances at an early stage

Imaging: TT, TEE: Vegetations and paravalvular abscesses as well as valve status

Cross-sectional imaging: CT and nuclear medicine imaging (PET: Positron emission tomography, SPECT /CT: Single-photon emission computed tomography(

Duke criteria (simplified) with additional criteria of the European Society of Cardiology (ESC(

Diagnosis is made using the Duke criteria. The presence of two main criteria, one major criteria  and three minor criteria or five minor criteria verifies the diagnosis.

The major criteria

1. Positive blood cultures: Two separate positive blood cultures with typical pathogen detection
2. Evidence of endocardial involvement in imaging: transesophageal echocardiography: heart valve vegetation, abscesses, (pseudo) aneurysms, fistulas, perforations and /or dehiscences of a valve prosthesis
3. Cross-sectional imaging: consequences of perivalvular lesions, including pseudoaneurysms and abscesses

Additional main criteria according to European Society of Cardiology (ESC) 2015

Evidence of paravalvular lesions in cardiac CT

Evidence of abnormal activity around a valve replacement in PET/CT or SPECT/CT

Minor criteria

1. Predisposition due to cardiac disease or i.v. drug abuse
2. Fever ≥38 ° C
3. Vascular changes: Arterial embolism, septic infarction, ICB
4. Immunological Disorder: Glomerulonephritis, Osler nodules, Roth's spots, pos. RF
5. Microbiology: Positive blood culture that does not fall under the main criteria
6. Additional incidental criterion after ESC 2015: Detection of (septic) embolic events (e.g., of the CNS) or infectious aneurysms in imaging

Therapy Principles

• antibiotic therapy
• For complicated cases : surgical therapy

Antibiotic therapy

• Initially calculated(empirical ) antibiotic therapy
• Adjust in the course according to the antibiogram

Duration of treatment:

• Native valve infection: 2-6 weeks
• Valve prosthesis infection: at least 6 weeks

Empirical antibiotic therapy of endocarditis (pathogen unknown)

All native valves and valve prosthesis> 12 months after surgery

• ampicillin
• And (flu) cloxacillin
• And gentamicin

In case of intolerance of  β-lactam antibiotics

• vancomycin
• and gentamicin

Valve prosthesis <12 months after surgery

• vancomycin
• And gentamicin
• And rifampicin

Prophylaxis
High-risk groups (where antibiotic prophylaxis is recommended)

• Patients with valve replacement (mechanical and biological)
• Patients with endocarditis
• Patients with congenital heart disease (cyanotic heart disease, All operatively or interventional using prosthetic material-treated heart defect (6 months after surgery))

Situations in which antibiotic prophylaxis should take place

• Interventions in oropharyngeal cavity (mainly dental treatments with manipulation of the gingiva, the periapical tooth region or perforation of the oral mucosa)
• Respiratory, gastrointestinal and urogenital infections as well as skin and soft tissue infections: here, the local pathogens, which are probably responsible, must be considered primarily in the choice of Antibiotic
• biopsies
• Vascular surgery involving the introduction of foreign material (including pacemakers or defibrillators)

Antibiotic prophylaxis

• Intervention area: Oropharyngeal cavity  (in particular dental risk interventions): Aminopenicillins: Amoxicillin (p.o.) or Ampicillin (i.v.), alternative (in case of allergy): Clindamycin
• Intervention area: Respiratory tract: aminopenicillin + beta-lactamase inhibitor or cefazolin, alternative (in case of allergy): clindamycin
• Intervention area: Skin: Oxacillin or Flucloxacillin, alternative (in case of allergy): Clindamycin
• Intervention area: Gastrointestinal and urogenital tract: ampicillin or piperacillin, alternative (in case of allergy): vancomycin

Proofreading: Amany Altabba