Infective endocarditis
Encyclopedia
Infective endocarditis is a form of endocarditis
, or inflammation, of the inner tissue of the heart, such as its valves, caused by infectious agents. The agents are usually bacterial, but other organisms can also be responsible.
The valves of the heart
do not receive any dedicated blood supply. As a result, defensive immune mechanisms (such as white blood cell
s) cannot directly reach the valves via the bloodstream. If an organism (such as bacteria) attaches to a valve surface and forms a vegetation, the host immune response is blunted. The lack of blood supply to the valves also has implications on treatment, since drugs also have difficulty reaching the infected valve.
Normally, blood flows smoothly through these valves. If they have been damaged - from rheumatic fever
, for example - the risk of bacterial attachment is increased.
This classification is now discouraged, because the ascribed associations (in terms of organism and prognosis) were not strong enough to be relied upon clinically. The terms short incubation (meaning less than about six weeks), and long incubation (greater than about six weeks) are preferred.
Culture-negative endocarditis can be due to micro-organisms that require a longer period of time to be identified in the laboratory, such organisms are said to be fastidious
because they have demanding growth requirements, or due to absence of an organism as in marantic endocarditis
. Some pathogens responsible for culture-negative endocarditis include Aspergillus
species, Brucella
species, Coxiella burnetii
, Chlamydia
species, and HACEK bacteria
. Another possible reason for culture negativity, even with the more typical pathogens, is prior antibiotic treatment.
lines, pacemakers, etc.
(where bacteria get into the blood stream through a minor cut or wound) would normally be cleared quickly with no adverse consequences. If a heart valve is damaged and covered with a piece of a blood clot, the valve provides a place for the bacteria to attach themselves and an infection can be established.
In the past, bacteremia caused by dental
procedures (in most cases due to viridans streptococci
, which reside in oral cavity), such as a cleaning or extraction
of a tooth
was thought to be more clinically significant than it actually was. However, it is important that a dentist
or a dental hygienist
be told of any heart problems before commencing treatment. Antibiotics are administered to patients with certain heart conditions as a precaution, although this practice has changed in the US, with new American Heart Association guidelines
released in 2007, and in the UK as of March 2008 due to new NICE guidelines. Everyday tooth brushing and flossing will similarly cause bacteremia. Although there is little evidence to support antibiotic prophylaxis for dental treatment, the current American Heart Association
guidelines are highly accepted by clinicians and patients.
Another group of causes results from a high number of bacteria getting into the bloodstream. Colorectal cancer
(mostly Streptococcus bovis
), serious urinary tract infection
s (mostly enterococci), and drug injection
(S. aureus) can all introduce large numbers of bacteria. With a large number of bacteria, even a normal heart valve may be infected. A more virulent organism (such as S. aureus, but see below for others) is usually responsible for infecting a normal valve.
Intravenous drug users tend to get their right-sided heart valves infected because the vein
s that are injected enter the right side of the heart, so they will have injured valves on that side, that the bacteria can bind to. In rheumatic heart disease infection occurs on the aortic and the mitral valves, on the left side of the heart.
Other factors that increase the risk of developing infective endocarditis are low levels of white blood cells
, immunodeficiency or immunosuppression, malignancy, diabetes
, and alcohol abuse.
, by auto-immune mechanisms, or simply as a consequence of old age. The damaged part of a heart valve becomes covered with a blood clot, a condition known as non-bacterial thrombotic endocarditis (NBTE). Altered blood flow, and thus infective endocarditis, are more likely in high pressure areas. Consequently, ventricular septal defects create more susceptibility than atrial septal defects. Damaged vascular endothelium will also promote platelet and fibrin deposition, upon which bacteria can take hold. Valvular lesions are a major cause of such damage, as are jet lesions resulting from ventricular septal defect
s or patent ductus arteriosus
.
In general, a patient should fulfill the Duke criteria in order to establish the diagnosis of endocarditis.
As the Duke criteria rely heavily on the results of echocardiography, research has addressed when to order an echocardiogram by using signs and symptoms to predict occult endocarditis among patients with intravenous drug abuse and among non drug-abusing patients. Unfortunately, this research is over 20 years old and it is possible that changes in the epidemiology of endocarditis and bacteria such as staphylococci make the following estimates incorrect.
Among patients who do not use intravenous drugs and have a fever in the emergency room, there is a less than 5% chance of occult endocarditis. Mellors in 1987 found no cases of endocarditis nor of staphylococcal bacteremia among 135 febrile patients in the emergency room. The upper confidence interval
for 0% of 135 is 5%, so for statistical reasons alone, there is up to a 5% chance of endocarditis among these patients. In contrast, Leibovici found that among 113 non-selected adults admitted to the hospital because of fever there were two cases (1.8% with 95%CI: 0% to 7%) of endocarditis.
Among patients who do use intravenous drugs and have a fever in the emergency room, there is about a 10% to 15% prevalence of endocarditis. This estimate is not substantially changed by whether the doctor believes the patient has a trivial explanation for their fever. Weisse found that 13% of 121 patients had endocarditis. Marantz also found a prevalence of endocarditis of 13% among such patients in the emergency room with fever. Samet found a 6% incidence among 283 such patients, but after excluding patients with initially apparent major illness to explain the fever (including 11 cases of manifest endocarditis), there was a 7% prevalence of endocarditis.
Among patients with staphylococcal bacteremia (SAB), one study found a 29% prevalence of endocarditis in community-acquired SAB versus 5% in nosocomial SAB. However, only 2% of strains were resistant to methicillin and so these numbers may be low in areas of higher resistance.
Major criteria include:
Minor criteria include:
, where the patient's blood is removed, and any growth is noted and identified. The term bacterial endocarditis (BE) commonly is used, reflecting the fact that most cases of IE are due to bacteria; however, Infective Endocarditis (IE) has become the preferred term.
Alpha-hemolytic
streptococci
, that are present in the mouth will often be the organism isolated if a dental procedure caused the bacteraemia. If the bacteraemia was introduced through the skin, such as contamination in surgery, during catheterisation, or in an IV drug user, S. aureus is common. A third important cause of endocarditis are bacteria of the genus Enterococcus
. These bacteria enter the bloodstream as a consequence of abnormalities in the gastrointestinal or urinary tracts. Enterococci are increasingly recognized as causes of nosocomial or hospital-acquired endocarditis. This contrasts with alpha-haemolytic streptococci and S. aureus which are causes of community-acquired endocarditis.
Some organisms, when isolated, give valuable clues to the cause, as they tend to be specific.
, a yeast
, is associated with IV drug users and the immunocompromised. Other fungi demonstrated to cause endocarditis are **Histoplasma capsulatum** and **Aspergillus
**. Tricosporon asahii is another proven agent.
Viral infections of the heart are usually associated with viral myocarditis or viral pericarditis. The existence of viral endocarditis is disputed, but there is some evidence that it can occur.
s are administered by the intravenous route to maximize diffusion of antibiotic molecules into vegetation(s) from the blood filling the chambers of the heart. This is necessary because neither the heart valves nor the vegetations adherent to them are supplied by blood vessels. Antibiotics are continued for a long time, typically two to six weeks. Specific drug regimens differ depending on the classification of the endocarditis as acute or subacute (acute necessitating treating for S. aureus with oxacillin
or vancomycin
in addition to gram-negative
coverage). Fungal endocarditis requires specific anti-fungal treatment, such as amphotericin B
.
In acute endocarditis, due to the fulminant inflammation empirical antibiotic therapy is started immediately after the blood has been drawn for culture. This usually includes oxacillin and gentamicin IV infusions until the culture sensitivity report with the minimum inhibitory concentration
comes, when the therapy can be modified to tailor to the microorganism
. There should be noted that the routine use of gentamicin to treat Staphylocococcal
endocarditis has been questioned, given the lack of evidence to support its use and the high rate of complications.
In subacute endocarditis, antibiotic treatment is based on the microorganism
involved, requiring the culture sensitivity report. So immediate therapy is mainly focused on symptomatic treatment.
The most common organism responsible for infective endocarditis are viridans-group streptococci
, which are highly sensitive to penicillin
. High dose IV crystalline penicillin every 4hrs for 2 weeks is recommended and still remains the drug of choice. Again it is important to note that antibiotic therapy hinges upon the culture sensitivity report.
Another regimen that is followed for endocarditis is the short course treatment which is a 2 week treatment regimen of benzyl penicillin
IV which may be sufficient for S. viridans and S. bovis so long as the following conditions are met:
‣ Endocarditis of a native valve, not on a prosthetic valve
‣ An MIC
≤ 0.1 mg/l
‣ No adverse prognostic factors such as heart failure, aortic valve regurgitation, or conduction defects
‣ No evidence of thromboembolism
‣ No vegetations > 5mm in diameter
‣ Clinical response within 7 days
The short course treatment
In patients where the blood culture
reveals the causative organism, culture sensitivity reports should be followed to treat the patient, in addition to usage of two bactericidal antibiotics for a minimum of two weeks as a combination therapy.
Surgical debridement of infected material and replacement of the valve with a mechanical or bioprosthetic artificial heart valve
is necessary in patients who fail to clear micro-organisms from their blood in response to antibiotic therapy, or in patients who develop cardiac failure resulting from destruction of a valve by infection. Other indications to consider surgery include:
‣ Unstable Prosthetic Valve or Obstruction
‣ Recurrent septic emboli, mycotic aneurysm
‣ Large vegetations
‣ Abscess formation
‣ Early closure of mitral valve
‣ Gram negative species
Infective endocarditis is associated with a 25% mortality.
Endocarditis
Endocarditis is an inflammation of the inner layer of the heart, the endocardium. It usually involves the heart valves . Other structures that may be involved include the interventricular septum, the chordae tendineae, the mural endocardium, or even on intracardiac devices...
, or inflammation, of the inner tissue of the heart, such as its valves, caused by infectious agents. The agents are usually bacterial, but other organisms can also be responsible.
The valves of the heart
Heart valve
A heart valve normally allows blood flow in only one direction through the heart. The four valves commonly represented in a mammalian heart determine the pathway of blood flow through the heart...
do not receive any dedicated blood supply. As a result, defensive immune mechanisms (such as white blood cell
White blood cell
White blood cells, or leukocytes , are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five different and diverse types of leukocytes exist, but they are all produced and derived from a multipotent cell in the bone marrow known as a...
s) cannot directly reach the valves via the bloodstream. If an organism (such as bacteria) attaches to a valve surface and forms a vegetation, the host immune response is blunted. The lack of blood supply to the valves also has implications on treatment, since drugs also have difficulty reaching the infected valve.
Normally, blood flows smoothly through these valves. If they have been damaged - from rheumatic fever
Rheumatic fever
Rheumatic fever is an inflammatory disease that occurs following a Streptococcus pyogenes infection, such as strep throat or scarlet fever. Believed to be caused by antibody cross-reactivity that can involve the heart, joints, skin, and brain, the illness typically develops two to three weeks after...
, for example - the risk of bacterial attachment is increased.
By duration
Historically, infective endocarditis has been clinically divided into acute and subacute presentations (because untreated patients tended to live longer with the subacute as opposed to the acute form). This classifies both the rate of progression and severity of disease.- Subacute bacterial endocarditis (SBE) is often due to streptococci of low virulence and mild to moderate illness which progresses slowly over weeks and months and has low propensity to hematogenously seed extracardiac sites.
- Acute bacterial endocarditis (ABE) is a fulminantFulminantFulminant is any event or process that occurs suddenly and quickly, and is intense and severe to the point of lethality, i.e., it has an explosive character. The word comes from Latin fulmināre, to strike with lightning...
illness over days to weeks, and is more likely due to Staphylococcus aureusStaphylococcus aureusStaphylococcus aureus is a facultative anaerobic Gram-positive coccal bacterium. It is frequently found as part of the normal skin flora on the skin and nasal passages. It is estimated that 20% of the human population are long-term carriers of S. aureus. S. aureus is the most common species of...
which has much greater virulence, or disease-producing capacity and frequently causes metastatic infection.
This classification is now discouraged, because the ascribed associations (in terms of organism and prognosis) were not strong enough to be relied upon clinically. The terms short incubation (meaning less than about six weeks), and long incubation (greater than about six weeks) are preferred.
By culture results
Infective endocarditis may also be classified as culture-positive or culture-negative.Culture-negative endocarditis can be due to micro-organisms that require a longer period of time to be identified in the laboratory, such organisms are said to be fastidious
Growth medium
A growth medium or culture medium is a liquid or gel designed to support the growth of microorganisms or cells, or small plants like the moss Physcomitrella patens.There are different types of media for growing different types of cells....
because they have demanding growth requirements, or due to absence of an organism as in marantic endocarditis
Marantic endocarditis
Marantic endocarditis, also known as non-bacterial thrombotic endocarditis , is the deposition of small sterile vegetations on valve leaflets....
. Some pathogens responsible for culture-negative endocarditis include Aspergillus
Aspergillus
Aspergillus is a genus consisting of several hundred mold species found in various climates worldwide. Aspergillus was first catalogued in 1729 by the Italian priest and biologist Pier Antonio Micheli...
species, Brucella
Brucella
Brucella is a genus of Gram-negative bacteria. They are small , non-motile, non-encapsulated coccobacilli, which function as facultative intracellular parasites....
species, Coxiella burnetii
Coxiella burnetii
Coxiella burnetii is an obligate intracellular bacterial pathogen, and is the causative agent of Q fever. The genus Coxiella is morphologically similar to Rickettsia, but with a variety of genetic and physiological differences. C...
, Chlamydia
Chlamydia (bacterium)
Chlamydia is a genus of bacteria that are obligate intracellular parasites. Chlamydia infections are the most common bacterial sexually transmitted infections in humans and are the leading cause of infectious blindness worldwide....
species, and HACEK bacteria
HACEK organism
A HACEK organism is one of a set of slow-growing Gram negative bacteria that form a normal part of the human flora.They are a frequent cause of endocarditis in children.-Organisms:The name is formed from their initials:...
. Another possible reason for culture negativity, even with the more typical pathogens, is prior antibiotic treatment.
By heart side
Endocarditis can also be classified by the side of the heart affected:- Patients who inject narcotics or other drugs intravenously may introduce infection which will travel to the right side of the heart classically affecting the tricuspid valveTricuspid valveThe tricuspid valve, or right atrioventricular valve, is on the right dorsal side of the mammalian heart, between the right atrium and the right ventricle. The normal tricuspid valve usually has three leaflets and three papillary muscles. They are connected to the papillary muscles by the chordae...
, and most often caused by S. aureus. - In other patients without a history of intravenous exposure, endocarditis is more frequently left-sided.
By infection type
Another form of endocarditis is nosocomial endocarditis which is when the patient is diagnosed with endocarditis and has had hospital care one month prior to the incident and is usually secondary to IV catheters, Total parenteral nutritionTotal parenteral nutrition
Parenteral nutrition is feeding a person intravenously, bypassing the usual process of eating and digestion. The person receives nutritional formulae that contain nutrients such as glucose, amino acids, lipids and added vitamins and dietary minerals...
lines, pacemakers, etc.
By valve type
Finally, the distinction between native-valve endocarditis and prosthetic-valve endocarditis is clinically important. Prosthetic valve endocarditis can be early (< 60 days of valvular surgery) or late (> 60 days of valvular surgery).- Early prosthetic valve endocarditis is usually due to intraoperative contamination or a postoperative bacterial contamination which is usually nosocomial in nature.
- Late prosthetic valve endocarditis is usually due to community acquired microorganisms.
Signs and symptoms
- FeverFeverFever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
, i.e. fever of unknown originFever of unknown originFever of unknown origin , pyrexia of unknown origin or febris e causa ignota refers to a condition in which the patient has an elevated temperature but despite investigations by a physician no explanation has been found....
occurs in 97% of people; malaise and endurance fatigue in 90% of people. - A new or changing heart murmurHeart murmurMurmurs are extra heart sounds that are produced as a result of turbulent blood flow that is sufficient to produce audible noise. Most murmurs can only be heard with the assistance of a stethoscope ....
, weight loss, and coughing occurs in 35% of people. - Vascular phenomena: septic embolismSeptic embolismA septic embolism is a type of embolism that is infected with bacteria, resulting in the formation of pus. These may become dangerous if dislodged from their original location. Like other emboli, a septic embolism may be fatal....
(causing thromboembolic problems such as strokeStrokeA stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
in the parietal lobeParietal lobeThe parietal lobe is a part of the Brain positioned above the occipital lobe and behind the frontal lobe.The parietal lobe integrates sensory information from different modalities, particularly determining spatial sense and navigation. For example, it comprises somatosensory cortex and the...
of the brainHuman brainThe human brain has the same general structure as the brains of other mammals, but is over three times larger than the brain of a typical mammal with an equivalent body size. Estimates for the number of neurons in the human brain range from 80 to 120 billion...
or gangreneGangreneGangrene is a serious and potentially life-threatening condition that arises when a considerable mass of body tissue dies . This may occur after an injury or infection, or in people suffering from any chronic health problem affecting blood circulation. The primary cause of gangrene is reduced blood...
of fingers), Janeway lesionJaneway lesionJaneway lesions are non-tender, small erythematous or haemorrhagic macular or nodular lesions on the palms or soles only a few millimeters in diameter that are pathognomonic of infective endocarditis. Pathologically, the lesion is described to be a microabscess of the dermis with marked necrosis...
s (painless hemorrhagic cutaneous lesions on the palms and soles), intracranial hemorrhage, conjunctivaConjunctivaThe conjunctiva covers the sclera and lines the inside of the eyelids. It is composed of rare stratified columnar epithelium.-Function:...
l hemorrhage, splinter hemorrhageSplinter hemorrhageSplinter hemorrhages are tiny lines that run vertically under nails. Splinter hemorrhage is a nonspecific finding and can be associated with subacute bacterial endocarditis, scleroderma, trichinosis, Systemic lupus erythematosus , rheumatoid arthritis, psoriatic nails, antiphospholipid syndrome,...
s, Renal Infarcts, and Infarct Spleen. - Immunologic phenomena: GlomerulonephritisGlomerulonephritisGlomerulonephritis, also known as glomerular nephritis, abbreviated GN, is a renal disease characterized by inflammation of the glomeruli, or small blood vessels in the kidneys...
which allows for blood and albumin to enter the urine, Osler's nodeOsler's nodeOsler's nodes are painful, red, raised lesions found on the hands and feet. They are associated with a number of conditions, including infective endocarditis, and are caused by immune complex deposition. They are named after Sir William Osler who described them in the early 20th century...
s (painful subcutaneous lesions in the distal fingers), Roth's spotRoth's spotRoth's spots are retinal hemorrhages with white or pale centers composed of coagulated fibrin. They are typically observed via fundoscopy or slit lamp exam....
s on the retinaRetinaThe vertebrate retina is a light-sensitive tissue lining the inner surface of the eye. The optics of the eye create an image of the visual world on the retina, which serves much the same function as the film in a camera. Light striking the retina initiates a cascade of chemical and electrical...
, positive serum rheumatoid factorRheumatoid factorRheumatoid factor is an autoantibody most relevant in rheumatoid arthritis. It is defined as an antibody against the Fc portion of IgG. RF and IgG join to form immune complexes that contribute to the disease process... - Other signs may include; night sweats, rigors, anemia, splenomegaly, clubbing
Cause
In a healthy individual, a bacteremiaBacteremia
Bacteremia is the presence of bacteria in the blood. The blood is normally a sterile environment, so the detection of bacteria in the blood is always abnormal....
(where bacteria get into the blood stream through a minor cut or wound) would normally be cleared quickly with no adverse consequences. If a heart valve is damaged and covered with a piece of a blood clot, the valve provides a place for the bacteria to attach themselves and an infection can be established.
In the past, bacteremia caused by dental
Dentistry
Dentistry is the branch of medicine that is involved in the study, diagnosis, prevention, and treatment of diseases, disorders and conditions of the oral cavity, maxillofacial area and the adjacent and associated structures and their impact on the human body. Dentistry is widely considered...
procedures (in most cases due to viridans streptococci
Streptococcus viridans
Viridans Streptococcus is a pseudotaxonomic non-Linnaenan term for a large group of commensal streptococcal bacteria that are either α-hemolytic, producing a green coloration on blood agar plates , or nonhemolytic...
, which reside in oral cavity), such as a cleaning or extraction
Extraction (dental)
A dental extraction is the removal of a tooth from the mouth. Extractions are performed for a wide variety of reasons, including tooth decay that has destroyed enough tooth structure to render the tooth non-restorable...
of a tooth
Tooth
Teeth are small, calcified, whitish structures found in the jaws of many vertebrates that are used to break down food. Some animals, particularly carnivores, also use teeth for hunting or for defensive purposes. The roots of teeth are embedded in the Mandible bone or the Maxillary bone and are...
was thought to be more clinically significant than it actually was. However, it is important that a dentist
Dentist
A dentist, also known as a 'dental surgeon', is a doctor that specializes in the diagnosis, prevention, and treatment of diseases and conditions of the oral cavity. The dentist's supporting team aides in providing oral health services...
or a dental hygienist
Dental hygienist
thumb|right|300px|Dental hygienist holding a scalerA dental hygienist is a licensed dental professional who specializes in preventive oral health, typically focusing on techniques in oral hygiene. Local dental regulations determine the scope of practice of dental hygienists...
be told of any heart problems before commencing treatment. Antibiotics are administered to patients with certain heart conditions as a precaution, although this practice has changed in the US, with new American Heart Association guidelines
Dental antibiotic prophylaxis
Dental antibiotic prophylaxis is the admission of antibiotics to a dental patient for prevention of harmful consequences of bacteremia, that may be caused by invasion of the oral flora into an injured gingival or peri-apical vessel during dental treatment...
released in 2007, and in the UK as of March 2008 due to new NICE guidelines. Everyday tooth brushing and flossing will similarly cause bacteremia. Although there is little evidence to support antibiotic prophylaxis for dental treatment, the current American Heart Association
American Heart Association
The American Heart Association is a non-profit organization in the United States that fosters appropriate cardiac care in an effort to reduce disability and deaths caused by cardiovascular disease and stroke. It is headquartered in Dallas, Texas...
guidelines are highly accepted by clinicians and patients.
Another group of causes results from a high number of bacteria getting into the bloodstream. Colorectal cancer
Colorectal cancer
Colorectal cancer, commonly known as bowel cancer, is a cancer caused by uncontrolled cell growth , in the colon, rectum, or vermiform appendix. Colorectal cancer is clinically distinct from anal cancer, which affects the anus....
(mostly Streptococcus bovis
Streptococcus bovis
Streptococcus bovis is a catalase- and oxidase-negative, non-motile, non-sporulating, Gram-positive lactic acid bacterium that grows as pairs or chains of cocci. It is a member of the Lancefield group D streptococci. Most strains are non- or gamma-hemolytic, but some also display alpha-hemolytic...
), serious urinary tract infection
Urinary tract infection
A urinary tract infection is a bacterial infection that affects any part of the urinary tract. Symptoms include frequent feeling and/or need to urinate, pain during urination, and cloudy urine. The main causal agent is Escherichia coli...
s (mostly enterococci), and drug injection
Drug injection
In substance dependence and recreational drug use, drug injection is a method of introducing a drug into the body with a hollow needle and a syringe which is pierced through the skin into the body...
(S. aureus) can all introduce large numbers of bacteria. With a large number of bacteria, even a normal heart valve may be infected. A more virulent organism (such as S. aureus, but see below for others) is usually responsible for infecting a normal valve.
Intravenous drug users tend to get their right-sided heart valves infected because the vein
Vein
In the circulatory system, veins are blood vessels that carry blood towards the heart. Most veins carry deoxygenated blood from the tissues back to the heart; exceptions are the pulmonary and umbilical veins, both of which carry oxygenated blood to the heart...
s that are injected enter the right side of the heart, so they will have injured valves on that side, that the bacteria can bind to. In rheumatic heart disease infection occurs on the aortic and the mitral valves, on the left side of the heart.
Other factors that increase the risk of developing infective endocarditis are low levels of white blood cells
Neutropenia
Neutropenia, from Latin prefix neutro- and Greek suffix -πενία , is a granulocyte disorder characterized by an abnormally low number of neutrophils, the most important type of white blood cell...
, immunodeficiency or immunosuppression, malignancy, diabetes
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
, and alcohol abuse.
Pathogenesis
As previously mentioned, altered blood flow around the valves is a risk factor in obtaining endocarditis. The valves may be damaged congenitally, from surgerySurgery
Surgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...
, by auto-immune mechanisms, or simply as a consequence of old age. The damaged part of a heart valve becomes covered with a blood clot, a condition known as non-bacterial thrombotic endocarditis (NBTE). Altered blood flow, and thus infective endocarditis, are more likely in high pressure areas. Consequently, ventricular septal defects create more susceptibility than atrial septal defects. Damaged vascular endothelium will also promote platelet and fibrin deposition, upon which bacteria can take hold. Valvular lesions are a major cause of such damage, as are jet lesions resulting from ventricular septal defect
Ventricular septal defect
A ventricular septal defect is a defect in the ventricular septum, the wall dividing the left and right ventricles of the heart.The ventricular septum consists of an inferior muscular and superior membranous portion and is extensively innervated with conducting cardiomyocytes.The membranous...
s or patent ductus arteriosus
Patent ductus arteriosus
Patent ductus arteriosus is a congenital disorder in the heart wherein a neonate's ductus arteriosus fails to close after birth. Early symptoms are uncommon, but in the first year of life include increased work of breathing and poor weight gain...
.
Diagnosis
As the Duke criteria rely heavily on the results of echocardiography, research has addressed when to order an echocardiogram by using signs and symptoms to predict occult endocarditis among patients with intravenous drug abuse and among non drug-abusing patients. Unfortunately, this research is over 20 years old and it is possible that changes in the epidemiology of endocarditis and bacteria such as staphylococci make the following estimates incorrect.
Among patients who do not use intravenous drugs and have a fever in the emergency room, there is a less than 5% chance of occult endocarditis. Mellors in 1987 found no cases of endocarditis nor of staphylococcal bacteremia among 135 febrile patients in the emergency room. The upper confidence interval
Confidence interval
In statistics, a confidence interval is a particular kind of interval estimate of a population parameter and is used to indicate the reliability of an estimate. It is an observed interval , in principle different from sample to sample, that frequently includes the parameter of interest, if the...
for 0% of 135 is 5%, so for statistical reasons alone, there is up to a 5% chance of endocarditis among these patients. In contrast, Leibovici found that among 113 non-selected adults admitted to the hospital because of fever there were two cases (1.8% with 95%CI: 0% to 7%) of endocarditis.
Among patients who do use intravenous drugs and have a fever in the emergency room, there is about a 10% to 15% prevalence of endocarditis. This estimate is not substantially changed by whether the doctor believes the patient has a trivial explanation for their fever. Weisse found that 13% of 121 patients had endocarditis. Marantz also found a prevalence of endocarditis of 13% among such patients in the emergency room with fever. Samet found a 6% incidence among 283 such patients, but after excluding patients with initially apparent major illness to explain the fever (including 11 cases of manifest endocarditis), there was a 7% prevalence of endocarditis.
Among patients with staphylococcal bacteremia (SAB), one study found a 29% prevalence of endocarditis in community-acquired SAB versus 5% in nosocomial SAB. However, only 2% of strains were resistant to methicillin and so these numbers may be low in areas of higher resistance.
Echocardiography
The transthoracic echocardiogram has a sensitivity and specificity of approximately 65% and 95% if the echocardiographer believes there is 'probable' or 'almost certain' evidence of endocarditis.Duke criteria
Established in 1994 by the Duke Endocarditis Society and revised in 2000, the Duke criteria are a collection of major and minor criteria used to establish a diagnosis of endocarditis. A diagnosis can be reached in any of three ways: two major criteria, one major and three minor criteria, or five minor criteria.Major criteria include:
- Positive blood culture with typical IE microorganism, defined as one of the following:
- Typical microorganism consistent with IE from 2 separate blood cultures, as noted below:
- Viridans-group streptococci, or
- S. bovis including nutritional variant strains, or
- HACEK group, or
- S. aureus, or
- Community-acquired enterococci, in the absence of a primary focus
- Microorganisms consistent with IE from persistently positive blood cultures defined as:
- Two positive cultures of blood samples drawn >12 hours apart, or
- All of 3 or a majority of 4 separate cultures of blood (with first and last sample drawn 1 hour apart)
- Coxiella burnetiiCoxiella burnetiiCoxiella burnetii is an obligate intracellular bacterial pathogen, and is the causative agent of Q fever. The genus Coxiella is morphologically similar to Rickettsia, but with a variety of genetic and physiological differences. C...
detected by at least one positive blood culture or antiphase I IgG antibody titer >1:800
- Typical microorganism consistent with IE from 2 separate blood cultures, as noted below:
- Evidence of endocardial involvement with positive echocardiogram defined as
- Oscillating intracardiac mass on valve or supporting structures, in the path of regurgitant jets, or on implanted material in the absence of an alternative anatomic explanation, or
- Abscess, or
- New partial dehiscence of prosthetic valve or new valvular regurgitation (worsening or changing of preexisting murmur not sufficient)
Minor criteria include:
- Predisposing factor: known cardiac lesion, recreational drug injectionDrug injectionIn substance dependence and recreational drug use, drug injection is a method of introducing a drug into the body with a hollow needle and a syringe which is pierced through the skin into the body...
- Fever >38°C
- Evidence of embolismEmbolismIn medicine, an embolism is the event of lodging of an embolus into a narrow capillary vessel of an arterial bed which causes a blockage in a distant part of the body.Embolization is...
: arterial emboli, pulmonary infarcts, Janeway lesions, conjunctival hemorrhage - Immunological problems: glomerulonephritisGlomerulonephritisGlomerulonephritis, also known as glomerular nephritis, abbreviated GN, is a renal disease characterized by inflammation of the glomeruli, or small blood vessels in the kidneys...
, Osler's nodes - Positive blood culture (that doesn't meet a major criterion) or serologic evidence of infection with organism consistent with IE but not satisfying major criterion
-
Positive echocardiogram (that doesn't meet a major criterion)(this criterion has been removed from the modified Duke criteria)
Micro-organisms responsible
Many microorganisms can cause infective endocarditis. These are generally isolated by blood cultureBlood culture
Blood culture is a microbiological culture of blood. It is employed to detect infections that are spreading through the bloodstream...
, where the patient's blood is removed, and any growth is noted and identified. The term bacterial endocarditis (BE) commonly is used, reflecting the fact that most cases of IE are due to bacteria; however, Infective Endocarditis (IE) has become the preferred term.
Bacterial
ViridansStreptococcus viridans
Viridans Streptococcus is a pseudotaxonomic non-Linnaenan term for a large group of commensal streptococcal bacteria that are either α-hemolytic, producing a green coloration on blood agar plates , or nonhemolytic...
Alpha-hemolytic
Hemolysis (microbiology)
Hemolysis is the breakdown of red blood cells. The ability of bacterial colonies to induce hemolysis when grown on blood agar is used to classify certain microorganisms. This is particularly useful in classifying streptococcal species...
streptococci
Streptococcus
Streptococcus is a genus of spherical Gram-positive bacteria belonging to the phylum Firmicutes and the lactic acid bacteria group. Cellular division occurs along a single axis in these bacteria, and thus they grow in chains or pairs, hence the name — from Greek στρεπτος streptos, meaning...
, that are present in the mouth will often be the organism isolated if a dental procedure caused the bacteraemia. If the bacteraemia was introduced through the skin, such as contamination in surgery, during catheterisation, or in an IV drug user, S. aureus is common. A third important cause of endocarditis are bacteria of the genus Enterococcus
Enterococcus
Enterococcus is a genus of lactic acid bacteria of the phylum Firmicutes. Enterococci are Gram-positive cocci that often occur in pairs or short chains, and are difficult to distinguish from streptococci on physical characteristics alone. Two species are common commensal organisms in the...
. These bacteria enter the bloodstream as a consequence of abnormalities in the gastrointestinal or urinary tracts. Enterococci are increasingly recognized as causes of nosocomial or hospital-acquired endocarditis. This contrasts with alpha-haemolytic streptococci and S. aureus which are causes of community-acquired endocarditis.
Some organisms, when isolated, give valuable clues to the cause, as they tend to be specific.
- PseudomonasPseudomonasPseudomonas is a genus of gammaproteobacteria, belonging to the family Pseudomonadaceae containing 191 validly described species.Recently, 16S rRNA sequence analysis has redefined the taxonomy of many bacterial species. As a result, the genus Pseudomonas includes strains formerly classified in the...
species, which are very resilient organisms that thrive in water, may contaminate street drugs that have been contaminated with drinking water. P. aeruginosaPseudomonas aeruginosaPseudomonas aeruginosa is a common bacterium that can cause disease in animals, including humans. It is found in soil, water, skin flora, and most man-made environments throughout the world. It thrives not only in normal atmospheres, but also in hypoxic atmospheres, and has, thus, colonized many...
can infect a child through foot punctures, and can cause both endocarditis and septic arthritisSeptic arthritisSeptic arthritis is the purulent invasion of a joint by an infectious agent which produces arthritis. People with artificial joints are more at risk than the general population but have slightly different symptoms, are infected with different organisms and require different treatment. Septic...
. - S. bovisStreptococcus bovisStreptococcus bovis is a catalase- and oxidase-negative, non-motile, non-sporulating, Gram-positive lactic acid bacterium that grows as pairs or chains of cocci. It is a member of the Lancefield group D streptococci. Most strains are non- or gamma-hemolytic, but some also display alpha-hemolytic...
and Clostridium septicumClostridium septicumClostridium septicum is a gram positive, spore forming, obligate anaerobic bacterium.Clostridium septicum can cause gas gangrene, but unlike other Clostridium species like Clostridium perfringens, no trauma is necessary at the site of the infection. It is thought that the infection is established...
, which are part of the natural flora of the bowel, are associated with colonic malignancies. When they present as the causative agent in endocarditis, it usually call for a concomitant colonoscopyColonoscopyColonoscopy is the endoscopic examination of the large bowel and the distal part of the small bowel with a CCD camera or a fiber optic camera on a flexible tube passed through the anus. It may provide a visual diagnosis and grants the opportunity for biopsy or removal of suspected...
due to worries regarding hematogenous spread of bacteria from the colon due to the neoplasm breaking down the barrier between the gut lumen and the blood vessels which drain the bowel. - HACEK organisms are a group of bacteria that live on the dental gums, and can be seen with IV drug users who contaminate their needles with saliva. Patients may also have a history of poor dental hygiene, or pre-existing valvular disease.
- Less commonly reported etiological bacteria are responsible for blood culture negative infectious endocartitis. Such bacteria are identified by serology, culture of the excised valve tissue, sputum, pleural fluid, and emboli; and by polymerase chain reaction or and sequencing of bacterial 16S ribosomal RNA. Such bacteria include Streptococcus mitisStreptococcus mitisStreptococcus mitis is a mesophilic alpha-hemolytic species of Streptococcus that inhabits the human mouth. It is a Gram positive, coccus, facultative anaerobe and catalase negative. It can cause endocarditis...
, BartonellaBartonellaBartonella is a genus of Gram-negative bacteria. Facultative intracellular parasites, Bartonella species can infect healthy people but are considered especially important as opportunistic pathogens. Bartonella are transmitted by insect vectors such as ticks, fleas, sand flies and mosquitoes...
, Chlamydia psittaci, and CoxiellaCoxiellaCoxiella refers to a genus of Gram-negative bacteria in the family Coxiellaceae. It is named after Harold Herald Rea Cox , an American bacteriologist. Coxiella burnetii is the only member of this genus...
Propianibacterium are normal skin flora, but have been responsible for deaths, due to the indolent course of this abscess producing infection. AbiotrophiaAbiotrophiaAbiotrophia is a genus of lactic acid bacteria, a family in the phylum Firmicutes .-Species:The genus contains 4 species of coccus shaped species, 2 are former members of the genus Streptococcus, which were transferred in 1995 to the newly coined genus Abiotrophia:* A. adiacens Abiotrophia is a...
is a separate genus of gram-positive cocci formerly classified as nutritionally variant streptococci. These organisms cause 1% to 2% of all infective endocarditis. Tropheryma whippleiTropheryma whippleiTropheryma whipplei, formerly called Tropheryma whippelii, is a bacterium and the causative organism of Whipple's disease.While T. whipplei is categorized with the Gram-positive Actinobacteria, the organism is commonly found to be Gram-negative or Gram-indeterminate when stained in the laboratory...
has caused endocarditis without gastrointestinal involvement. Granulicatella elegans is another seldom proven etiology. Citrobacter koseriCitrobacter koseriCitrobacter koseri is a species of Citrobacter.It can cause brain abscesses with meningitis.-References:...
was found in an immunocompetent adult. Neisseria bacilliformis was found in a patient with a bicuspid aortic valve.
Fungal and viral
Candida albicansCandida albicans
Candida albicans is a diploid fungus that grows both as yeast and filamentous cells and a causal agent of opportunistic oral and genital infections in humans. Systemic fungal infections including those by C...
, a yeast
Yeast
Yeasts are eukaryotic micro-organisms classified in the kingdom Fungi, with 1,500 species currently described estimated to be only 1% of all fungal species. Most reproduce asexually by mitosis, and many do so by an asymmetric division process called budding...
, is associated with IV drug users and the immunocompromised. Other fungi demonstrated to cause endocarditis are **Histoplasma capsulatum** and **Aspergillus
Aspergillus
Aspergillus is a genus consisting of several hundred mold species found in various climates worldwide. Aspergillus was first catalogued in 1729 by the Italian priest and biologist Pier Antonio Micheli...
**. Tricosporon asahii is another proven agent.
Viral infections of the heart are usually associated with viral myocarditis or viral pericarditis. The existence of viral endocarditis is disputed, but there is some evidence that it can occur.
Treatment
High dose antibioticAntibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
s are administered by the intravenous route to maximize diffusion of antibiotic molecules into vegetation(s) from the blood filling the chambers of the heart. This is necessary because neither the heart valves nor the vegetations adherent to them are supplied by blood vessels. Antibiotics are continued for a long time, typically two to six weeks. Specific drug regimens differ depending on the classification of the endocarditis as acute or subacute (acute necessitating treating for S. aureus with oxacillin
Oxacillin
Oxacillin sodium is a narrow spectrum beta-lactam antibiotic of the penicillin class.It was developed by Beecham.-Uses:...
or vancomycin
Vancomycin
Vancomycin INN is a glycopeptide antibiotic used in the prophylaxis and treatment of infections caused by Gram-positive bacteria. It has traditionally been reserved as a drug of "last resort", used only after treatment with other antibiotics had failed, although the emergence of...
in addition to gram-negative
Gram-negative
Gram-negative bacteria are bacteria that do not retain crystal violet dye in the Gram staining protocol. In a Gram stain test, a counterstain is added after the crystal violet, coloring all Gram-negative bacteria with a red or pink color...
coverage). Fungal endocarditis requires specific anti-fungal treatment, such as amphotericin B
Amphotericin B
Amphotericin B is a polyene antifungal drug, often used intravenously for systemic fungal infections...
.
In acute endocarditis, due to the fulminant inflammation empirical antibiotic therapy is started immediately after the blood has been drawn for culture. This usually includes oxacillin and gentamicin IV infusions until the culture sensitivity report with the minimum inhibitory concentration
Minimum inhibitory concentration
In microbiology, minimum inhibitory concentration is the lowest concentration of an antimicrobial that will inhibit the visible growth of a microorganism after overnight incubation. Minimum inhibitory concentrations are important in diagnostic laboratories to confirm resistance of microorganisms...
comes, when the therapy can be modified to tailor to the microorganism
Microorganism
A microorganism or microbe is a microscopic organism that comprises either a single cell , cell clusters, or no cell at all...
. There should be noted that the routine use of gentamicin to treat Staphylocococcal
Staphylococcus aureus
Staphylococcus aureus is a facultative anaerobic Gram-positive coccal bacterium. It is frequently found as part of the normal skin flora on the skin and nasal passages. It is estimated that 20% of the human population are long-term carriers of S. aureus. S. aureus is the most common species of...
endocarditis has been questioned, given the lack of evidence to support its use and the high rate of complications.
In subacute endocarditis, antibiotic treatment is based on the microorganism
Microorganism
A microorganism or microbe is a microscopic organism that comprises either a single cell , cell clusters, or no cell at all...
involved, requiring the culture sensitivity report. So immediate therapy is mainly focused on symptomatic treatment.
The most common organism responsible for infective endocarditis are viridans-group streptococci
Streptococcus viridans
Viridans Streptococcus is a pseudotaxonomic non-Linnaenan term for a large group of commensal streptococcal bacteria that are either α-hemolytic, producing a green coloration on blood agar plates , or nonhemolytic...
, which are highly sensitive to penicillin
Penicillin
Penicillin is a group of antibiotics derived from Penicillium fungi. They include penicillin G, procaine penicillin, benzathine penicillin, and penicillin V....
. High dose IV crystalline penicillin every 4hrs for 2 weeks is recommended and still remains the drug of choice. Again it is important to note that antibiotic therapy hinges upon the culture sensitivity report.
Another regimen that is followed for endocarditis is the short course treatment which is a 2 week treatment regimen of benzyl penicillin
Penicillin
Penicillin is a group of antibiotics derived from Penicillium fungi. They include penicillin G, procaine penicillin, benzathine penicillin, and penicillin V....
IV which may be sufficient for S. viridans and S. bovis so long as the following conditions are met:
‣ Endocarditis of a native valve, not on a prosthetic valve
‣ An MIC
Minimum inhibitory concentration
In microbiology, minimum inhibitory concentration is the lowest concentration of an antimicrobial that will inhibit the visible growth of a microorganism after overnight incubation. Minimum inhibitory concentrations are important in diagnostic laboratories to confirm resistance of microorganisms...
≤ 0.1 mg/l
‣ No adverse prognostic factors such as heart failure, aortic valve regurgitation, or conduction defects
Heart block
A heart block can be a blockage at any level of the electrical conduction system of the heart .* Blocks that occur within the sinoatrial node are described as SA nodal blocks....
‣ No evidence of thromboembolism
‣ No vegetations > 5mm in diameter
‣ Clinical response within 7 days
The short course treatment
In patients where the blood culture
Blood culture
Blood culture is a microbiological culture of blood. It is employed to detect infections that are spreading through the bloodstream...
reveals the causative organism, culture sensitivity reports should be followed to treat the patient, in addition to usage of two bactericidal antibiotics for a minimum of two weeks as a combination therapy.
Surgical debridement of infected material and replacement of the valve with a mechanical or bioprosthetic artificial heart valve
Artificial heart valve
An artificial heart valve is a device implanted in the heart of a patient with heart valvular disease. When one of the four heart valves malfunctions, the medical choice may be to replace the natural valve with an artificial valve. This requires open-heart surgery.Valves are integral to the normal...
is necessary in patients who fail to clear micro-organisms from their blood in response to antibiotic therapy, or in patients who develop cardiac failure resulting from destruction of a valve by infection. Other indications to consider surgery include:
‣ Unstable Prosthetic Valve or Obstruction
‣ Recurrent septic emboli, mycotic aneurysm
‣ Large vegetations
‣ Abscess formation
‣ Early closure of mitral valve
‣ Gram negative species
Infective endocarditis is associated with a 25% mortality.