infective endocarditis

What is endocarditis

Endocarditis is is a rare, life-threatening infection that affects the inner lining of the heart (the endocardium), including the heart valves. Endocarditis occurs when bacteria, fungi or other germs from another part of your body, such as your mouth, enter your bloodstream, travel to your heart, and lodge on abnormal heart valves or damaged heart tissue. Abnormal growths (vegetations) that contain collections of bacteria may form in your heart at the site of the infection and damage the heart valves, which can cause them to leak. Streptococci (viridans-group streptococci) and staphylococci (Staphylococcus aureus) have collectively accounted for approximately 80% of infective endocarditis cases 1).

Infective endocarditis is an uncommon infectious disease with an annual incidence ranging from 1.5 to 11.6 per 100 000 person-years in the most contemporary population surveys 2). In the United States, there are up to 34,000 hospital discharges related to infective endocarditis each year. Men, women and children of all racial and ethnic groups can get endocarditis.

Despite recent advances in diagnostic and therapeutic strategies, the mortality of infective endocarditis remains high, with more than one-third of patients affected dying within a year following diagnosis 3).

Globally, in 2010, infective endocarditis was associated with 1.58 million disability-adjusted life-years or years of healthy life lost as a result of death and nonfatal illness or impairment 4).

Endocarditis is a rare, but potentially fatal condition that can cause damage your heart, so it requires early diagnosis and treatment. If it’s not treated quickly, endocarditis can damage or destroy your heart valves and can lead to life-threatening complications. Treatments for endocarditis include antibiotics and, in certain cases, surgery.

Since there are many ways to develop endocarditis, your doctor might not be able to pinpoint the exact cause of your condition. However, people at greatest risk of endocarditis usually have damaged heart valves, artificial heart valves or other heart defects.

Although the heart is usually well protected against infection, it may be easier for bacteria to bypass the immune system in people who have:

  • a prosthetic (artificial) heart valve – valve replacement surgery is increasingly being used when people experience narrowing of one of their heart valves
  • congenital heart disease – where a person is born with heart defects
  • hypertrophic cardiomyopathy – where the heart muscle cells have enlarged and the walls of the heart chambers thicken
  • damaged heart valves – because of infection or heart disease

People who inject drugs are also more likely to develop endocarditis.

In approximately 10% of cases of infective endocarditis, blood cultures are negative, most commonly due to patient receipt of antibiotics prior to the diagnostic work-up. ‘True’ culture-negative infective endocarditis is caused by fastidious microorganisms that are difficult to isolate with conventional microbiological techniques. Highly specialized assays such as serologic testing and polymerase-chain-reaction (PCR) using blood or valve biopsies can ultimately suggest a causative pathogen in up to 60% of such cases 5). Although the aetiology of true culture-negative infective endocarditis varies with geographic and epidemiologic factors, important causes include Coxiella burnetii (the causative agent of Q fever), Bartonella species, Brucella species, and Tropheryma whipplei 6). Specific risk factors such as contact with livestock or abattoirs (for Brucella and Coxiella), homelessness or alcoholism (for Bartonella quintana), travel to the Middle East or Mediterranean or consumption of unpasteurized dairy products (for Brucella), contact with cats (for Bartonella henselae) or extensive healthcare contact in a patient with a prosthetic valve and negative blood cultures (for Aspergillus) may be useful clues when evaluating potential infective endocarditis cases.

Infective endocarditis disease process can follow one of several courses resulting in the frequently made clinical distinction between sub-acute bacterial endocarditis and acute bacterial endocarditis. Sub-acute bacterial endocarditis usually occurs on normal valves and follows a smouldering course of many weeks. Micro-organisms from a source of sepsis attach to the heart valves and proliferate there, inducing further thrombosis and the formation of vegetations. The presence of bacteremia and generalized sepsis may also cause a peripheral syndrome of vasculitic changes. The significant outcomes of sub-acute bacterial endocarditis include heart failure, embolisms of vegetation fragments and abscess formation. Acute bacterial endocarditis occurs more commonly in intravenous drug abusers and on prosthetic valves and or after acute suppurative illness such as pneumonia and meningitis and follows a much more fulminant course with vasculitis and abscesses in other organs. The vasculitic syndromes (inflammation of blood vessels) can produce renal failure. infective endocarditis can also produce almost any valvular heart disorder. Sometimes, endocarditis can cause severe damage to your heart which can lead to heart failure.

Infective endocarditis is almost universally fatal if untreated. Untreated, the average time from onset of disease to death in sub-acute bacterial endocarditis is about 6 months, 4 weeks in acute bacterial endocarditis. Heart Failure is by far the strongest negative prognostic indicator. Despite advances in antibacterial therapies, early and late mortality rates in patients with infective endocarditis remain high, due to co-morbidities and late detection of the disease.

Figure 1. The anatomy of the heart

Heart-Anatomy

Figure 2. The anatomy of the heart valves

heart valves anatomy

Figure 3. Top view of the 4 heart valves

The-Four-Valves-of-the-Heart

Figure 4.  Normal heart blood flow

Normal_Heart_Anatomy_and_Blood_Flow

Figure 5. Heart valves function

heart valves function

Figure 6. Endocarditis

Endocarditis

Endocarditis complications

In endocarditis, clumps of bacteria and cell fragments form in your heart at the site of the infection. These clumps, called vegetations, can break loose and travel to your brain, lungs, abdominal organs, kidneys or limbs. As a result, endocarditis can cause several major complications, including:

  • Heart problems, such as heart murmur, heart valve damage and heart failure
  • Stroke
  • Seizure
  • Loss of the ability to move part of all of your body (paralysis)
  • Pockets of collected pus (abscesses) that develop in the heart, brain, lungs and other organs
  • Pulmonary embolism — an infected vegetation that travels to the lungs and blocks a lung artery
  • Kidney damage
  • Enlarged spleen

Endocarditis causes

Endocarditis occurs when germs enter your bloodstream, travel to your heart, and attach to abnormal heart valves or damaged heart tissue. Certain types of bacteria cause most cases, but fungi or other microorganisms also may be responsible.

Usually, your immune system destroys harmful bacteria that make it into your bloodstream. Even if bacteria reach your heart, they may pass through without causing an infection. However, bacteria that live in your mouth, throat or other parts of your body, such as your skin or your gut, can sometimes cause serious infections like endocarditis under the right circumstances.

Bacteria, fungi or other germs that cause endocarditis might enter your bloodstream through:

  • Everyday oral activities. Activities such as brushing your teeth, or other activities that could cause your gums to bleed, can allow bacteria to enter your bloodstream — especially if you don’t floss or your teeth and gums aren’t healthy.
  • An infection or other medical condition. Bacteria may spread from an infected area, such as a skin sore. Other medical conditions, such as gum disease, a sexually transmitted infection or certain intestinal disorders — such as inflammatory bowel disease — can also give bacteria the opportunity to enter your bloodstream.
  • Catheters. Bacteria can enter your body through a catheter — a thin tube that doctors sometimes use to inject or remove fluid from the body. This is more likely to occur if the catheter is in place for a long period of time.
  • Needles used for tattoos and body piercing. The bacteria that can cause endocarditis can also enter your bloodstream through the needles used for tattooing or body piercing.
  • Intravenous (IV) illegal drug use. Contaminated needles and syringes are a special concern for people who use illegal intravenous (IV) drugs, such as heroin or cocaine. Often, individuals who use these types of drugs don’t have access to clean, unused needles or syringes.
  • Certain dental procedures. Some dental procedures that can cut your gums may allow bacteria to enter your bloodstream.

Bacteria can more easily attach to the lining of your heart (endocardium), if the lining’s surface is rough. You’re also more likely to develop endocarditis if you have faulty, diseased or damaged heart valves. However, endocarditis does occasionally occur in previously healthy individuals.

Pathogenesis of endocarditis

The normal heart valve endothelium is resistant to bacterial colonization upon intravascular challenge 7). Thus, the development of infective endocarditis requires the simultaneous occurrence of several independent factors: alteration of the cardiac valve surface to produce a suitable site for bacterial attachment and colonization; bacteraemia with an organism capable of attaching to and colonizing valve tissue; and creation of the infected mass or ‘vegetation’ by ‘burying’ of the proliferating organism within a protective matrix of serum molecules (for example, fibrin) and platelets (Figure 7).

Figure 7. Pathogenesis of endocarditis

Pathogenesis of endocarditis

Note: a. Pathogens gain access to the bloodstream, for example via an intravenous catheter, injection drug use or from a dental source. b Pathogens adhere to an area of abnormal cardiac valve surface. c Some pathogens, such as S. aureus, obtain intracellular access to the valve endothelium. d The infected vegetation is created by burying of the proliferating organism within a protective matrix of serum molecules. e –Vegetation particles can detach and disseminate to form emboli. These may lead to complications such as ischemic stroke, mycotic aneurysms and infarcts or abscesses at remote sites.

Marantic endocarditis

Marantic endocarditis, otherwise known as nonbacterial thrombotic endocarditis, is a well-documented phenomenon due to hypercoagulability from an underlying cause. While any of the cardiac valves may be involved, the mitral valve and/or aortic valve are the most common sites at which this process occurs. Marantic endocarditis has been associated with a variety of inflammatory states including malignancy 8).  Marantic endocarditis is the result of a prothrombotic condition characterized by deposition of sterile fibrin and platelet-rich thrombi on previously undamaged heart valves. Cardiac function is generally unaffected.

The likelihood of systemic embolism secondary to marantic endocarditis is high (42%–50%) 9). Clinical presentation is most often a sudden neurological deficit. Associated morbidity and mortality are due to increased frequency of arterial embolic events, specifically in the central nervous system 10). The incidence of stroke due to marantic endocarditis (33%) is higher compared to infective endocarditis (19%) 11). Infarcts (strokes) due to marantic endocarditis tend to be multiple and variable-sized, with different characteristics from infarcts due to intracranial stenosis; the latter are commonly encountered in Asians and follow particular arterial territories 12).

The preferred diagnostic test for marantic endocarditis is a transesophageal echocardiography (TEE), which is more sensitive in the detection of valvular vegetations than the transthoracic approach 13). Recommended treatment is therapeutic anticoagulation with unfractionated heparin or LMWH (low molecular weight heparin) and treatment of the underlying cause 14). However, Pons et al 15) reported that anticoagulation with intravenous heparin does not play a role in the prevention of strokes in marantic endocarditis. Furthermore, there have been no studies defining the optimal treatment of marantic endocarditis. Also, the benefit of heparin compared to warfarin in the treatment of marantic endocarditis has not been studied.

A review of the literature from the past 3 decades reveals multiple case reports associating marantic endocarditis with various malignancies, most commonly of gynecologic origin 16). Surprisingly, although hypercoagulability is most often seen in patients with pancreatic cancer, marantic endocarditis has rarely been reported antemortem in this population 17). A prospective echocardiographic study of 200 living patients with solid tumors demonstrated a high prevalence of cardiac valvular vegetations with an overall incidence of 19%, including 3 of 6 pancreatic cancer patients (50%) 18). Recently, Smeglin et al. 19) documented the first case of an antemortem diagnosis of marantic endocarditis as the initial presentation of an underlying pancreatic cancer.

This study 20) suggests that prompt recognition and treatment of marantic endocarditis along with effective treatment of the underlying malignancy may improve the dismal prognosis of this syndrome.

Libman Sacks endocarditis

Libman-Sacks endocarditis, best characterized by Libman-Sacks vegetations, is common in systemic lupus erythematosus (SLE) and antiphospholipid syndrome 21). Libman-Sacks vegetations are sterile abnormal growths of tissue around the heart valves with an autoimmune-mediated inflammatory and thrombotic pathogenesis 22). The pathologic changes of Libman-Sacks endocarditis involve the formation of fibrin-platelet thrombi on the altered valve, the organization of which leads to valve fibrosis, edema, diffuse thickening, mild inflammatory changes, valve distortion, scarring, and subsequent valvular dysfunction such like stenosis or regurgitation 23). Libman-Sacks endocarditis often involve left heart valves, tricuspid lesions were very rare. And most Libman-Sacks endocarditis can be treated with medicine therapy while very few need surgical treatment.

Libman-Sacks vegetations are strong independent risk or pathogenic factors for stroke or TIA (transient ischemic attack or mini-stroke), focal brain lesions on MRI, or cognitive disability and can be further complicated with acute or chronic severe valve regurgitation, superimposed infective endocarditis, need for high risk valve surgery, and ultimately with death 24).

Risk factors for endocarditis

If your heart is healthy, you could be less likely to develop endocarditis, although it is still possible. The germs that cause infection tend to stick to and multiply on damaged or surgically implanted heart valves, or on endocardium that has a rough surface.

People at highest risk of endocarditis are those who have:

  • Artificial heart valves. Germs are more likely to attach to an artificial (prosthetic) heart valve than to a normal heart valve.
  • Congenital heart defects. If you were born with certain types of heart defects, such as an irregular heart or abnormal heart valves, your heart may be more susceptible to infection.
  • A history of endocarditis. Endocarditis can damage heart tissue and valves, increasing the risk of a future heart infection.
  • Damaged heart valves. Certain medical conditions, such as rheumatic fever or infection, can damage or scar one or more of your heart valves. This can make them more prone to endocarditis.
  • A history of intravenous (IV) illegal drug use. People who use illegal drugs by injecting them are at a greater risk of endocarditis. The needles used to inject drugs can be contaminated with the bacteria that can cause endocarditis.
  • Heart valve disease – either stenosis (a narrowed valve) or regurgitation (a leaking valve)
  • Heart devices (such as a pacemaker or implantable cardioverter defibrillator)

Endocarditis prevention

You can help prevent endocarditis in several ways, including:

  • Know the signs and symptoms of endocarditis. See your doctor immediately if you develop any signs or symptoms, especially a fever that won’t go away, unexplained fatigue, any type of skin infection, or open cuts or sores that don’t heal properly.
  • Pay special attention to your dental health — brush and floss your teeth and gums often, and have regular dental checkups.
  • Avoid procedures that may lead to skin infections, such as body piercings or tattoos.

Preventive antibiotics

Certain dental and medical procedures may allow bacteria to enter your bloodstream. For some people with heart disease or damaged or diseased heart valves, taking antibiotics before these procedures can help destroy or control the harmful bacteria that may lead to endocarditis. This is because these people are more at risk of developing endocarditis after having these procedures.

In the past, doctors gave antibiotics to many people before dental or other surgical procedures, such as procedures involving the intestinal or urinary tracts, even if they weren’t at high risk of developing endocarditis. However, antibiotics are no longer recommended before all dental or other surgical procedures, or for all people. As doctors have learned more about endocarditis prevention, they’ve realized endocarditis is much more likely to occur from exposure to random germs than from a standard dental exam or surgery.

For patients whose heart conditions put them at the highest risk for adverse events from infective endocarditis, the American Heart Association 25) recommends antibiotics before certain dental procedures. These include procedures that involve manipulation of gingival tissue or the periapical region of teeth, or perforation of the oral mucosa.

The American Heart Association has an endocarditis wallet card in English and Spanish. People who have been told that they need to take antibiotics should carry it. You can get it from here: http://www.heart.org/idc/groups/heart-public/@wcm/@hcm/documents/downloadable/ucm_307644.pdf

Show the card to your dentist or physician. It will help them take the precautions needed to protect your health.

If you’re at risk of endocarditis, let your doctor and dentist know before having any dental work. They will decide whether you need antibiotics before any dental procedures.

It’s still important to take good care of your teeth through brushing and flossing, since doctors have some concern that infections in your mouth from poor oral hygiene might increase the risk of germs entering your bloodstream. In addition to brushing and flossing, regular dental exams are an important part of maintaining good oral health.

Endocarditis guidelines

Endocarditis prophylaxis – American Heart Association Guidelines

Dental Procedures and Infective Endocarditis

In the past, patients with nearly every type of congenital heart defect needed to receive antibiotics one hour before dental procedures or operations on the mouth, throat, gastrointestinal genital, or urinary tract. However, in 2007 the American Heart Association simplified its recommendations. Today, antibiotics before dental procedures are only recommended for patients with the highest risk of infective endocarditis, those who have 26):

  1. A prosthetic heart valve or who have had a heart valve repaired with prosthetic material.
  2. A history of endocarditis.
  3. A heart transplant with abnormal heart valve function
  4. Certain congenital heart defects including:
    • Cyanotic congenital heart disease (birth defects with oxygen levels lower than normal), that has not been fully repaired, including children who have had a surgical shunts and conduits.
    • A congenital heart defect that’s been completely repaired with prosthetic material or a device for the first six months after the repair procedure. †
    • Repaired congenital heart disease with residual defects, such as persisting leaks or abnormal flow at or adjacent to a prosthetic patch or prosthetic device.

Key changes for patients with congenital heart defects

Preventive antibiotics are no longer recommended for any other congenital heart disease than these:

  • Cyanotic congenital heart disease (birth defects with oxygen levels lower than normal), that has not been fully repaired, including children who have had a surgical shunts and conduits.
  • A congenital heart defect that’s been completely repaired with prosthetic material or a device for the first six months after the repair procedure. †
  • Repaired congenital heart disease with residual defects, such as persisting leaks or abnormal flow at or adjacent to a prosthetic patch or prosthetic device.

Additionally, taking antibiotics just to prevent endocarditis is not recommended for patients who have procedures involving the reproductive, urinary or gastrointestinal tracts.

Note: † Prophylaxis is reasonable because endothelialization of prosthetic material occurs within six months after the procedure.

Antibiotic prophylaxis against infective endocarditis is not recommended routinely:

  • for people undergoing dental procedures
  • for people undergoing non‑dental procedures at the following sites:
    • upper and lower gastrointestinal tract
    • genitourinary tract; this includes urological, gynaecological and obstetric procedures, and childbirth
    • upper and lower respiratory tract; this includes ear, nose and throat procedures and bronchoscopy.

Chlorhexidine mouthwash should not be offered as prophylaxis against infective endocarditis to people at risk of infective endocarditis undergoing dental procedures.

Antibiotic Regimens

An antibiotic for prophylaxis should be administered in a single dose before the procedure. If the dosage of antibiotic is inadvertently not administered before the procedure, the dosage may be administered up to 2 hours after the procedure. However, administration of the dosage after the procedure should be considered only when the patient did not receive the pre-procedure dose. Some patients who are scheduled for an invasive procedure may have a coincidental endocarditis. The presence of fever or other manifestations of systemic infection should alert the provider to the possibility of infective endocarditis. In these circumstances, it is important to obtain blood cultures and other relevant tests before administration of antibiotics intended to prevent infective endocarditis. Failure to do so may result in delay in diagnosis or treatment of a concomitant case of infective endocarditis.

Table 1. Antibiotic Regimens for a Dental Procedure

SituationAgentRegimen: Single Dose 30 to 60 min Before Procedure
AdultsChildren
IM indicates intramuscular; IV, intravenous.
*Or other first- or second-generation oral cephalosporin in equivalent adult or pediatric dosage.
†Cephalosporins should not be used in an individual with a history of anaphylaxis, angioedema, or urticaria with penicillins or ampicillin.
OralAmoxicillin2 g50 mg/kg
Unable to take oral medicationAmpicillin OR Cefazolin or ceftriaxone2 g IM or IV50 mg/kg IM or IV
1 g IM or IV50 mg/kg IM or IV
Allergic to penicillins or ampicillin—oralCephalexin* OR Clindamycin OR Azithromycin or clarithromycin2 g50 mg/kg
600 mg20 mg/kg
500 mg15 mg/kg
Allergic to penicillins or ampicillin and unable to take oral medicationCefazolin or ceftriaxone OR Clindamycin1 g IM or IV50 mg/kg IM or IV
600 mg IM or IV20 mg/kg IM or IV
[Source 27)]

Adults and children with structural cardiac defects at risk of developing infective endocarditis

The following cardiac conditions as being at increased risk of developing infective endocarditis:

  • acquired valvular heart disease with stenosis or regurgitation
  • hypertrophic cardiomyopathy
  • previous infective endocarditis
  • structural congenital heart disease, including surgically corrected or palliated structural conditions, but excluding isolated atrial septal defect, fully repaired ventricular septal defect or fully repaired patent ductus arteriosus, and closure devices that are judged to be endothelialised
  • valve replacement.

Infective endocarditis signs and symptoms

Endocarditis may develop slowly or suddenly, depending on what germs are causing the infection and whether you have any underlying heart problems. Endocarditis signs and symptoms can vary from person to person.

Common signs and symptoms of endocarditis include:

  • Flu-like symptoms, such as fever and chills
  • A new or changed heart murmur, which is the heart sounds made by blood rushing through your heart
  • Fatigue
  • Aching joints and muscles
  • Night sweats
  • Shortness of breath
  • Chest pain when you breathe
  • Swelling in your feet, legs or abdomen

Endocarditis can also cause symptoms that are more uncommon. These include:

  • Unexplained weight loss
  • Blood in your urine, which you might be able to see or that your doctor might see when he or she views your urine under a microscope
  • Tenderness in your spleen, which is an infection-fighting abdominal organ just below your rib cage on the left side of your body
  • Janeway lesions, which are red spots on the soles of your feet or the palms of your hands
  • Osler’s nodes, which are red, tender spots under the skin of your fingers or toes
  • Petechiae, which are tiny purple or red spots on the skin, whites of your eyes, or inside your mouth

endocarditis symptoms

Signs of endocarditis

Figure 8. Osler’s nodes (tender red spots or nodules under the skin of the toes)

Osler's nodes

Figure 9. Janeway lesions (A, Nontender, small purpuric spots on all toes. B, Linear reddish-brown streaks on the distal portions of the nail plates of all fingers)

Janeway lesions

Figure 10. Janeway lesions (non-tender hemorrhagic macules and papules over the palms and volar aspect of the fingers)

Janeway lesions
Janeway lesions

Figure 11. Conjunctival Petechiae

Infective Endocarditis conjunctival petechiae

Figure 12. Conjunctival Hemorrhage

Infective Endocarditis conjunctival hemorrhages

Figure 13. Infective Endocarditis – Retinal Roth Spots (retinal hemorrhages) – image on the right is a close up image of a Roth spot showing a central clearing

Infective Endocarditis retinal Roth spot

Endocarditis diagnosis

Your doctor may suspect endocarditis based on your medical history, signs and symptoms you’re experiencing, and your test results. A diagnosis of endocarditis is usually based on several factors instead of a single positive test result or symptom.

Your doctor may order several tests to help make a positive diagnosis, including:

  • Blood tests. A blood culture test is used to identify any bacteria or fungi in your bloodstream, and it’s the most important test your doctor will perform. Blood tests can also help your doctor identify certain conditions that can be a sign of endocarditis, such as anemia — a shortage of healthy red blood cells.
  • Echocardiogram. An echocardiogram uses sound waves to produce images of your heart while it’s beating. This test is often used to check for signs of infection. Your doctor may use two different types of echocardiograms to help diagnose endocarditis. In a transthoracic echocardiogram, sound waves directed at your heart from a wandlike device (transducer) held on your chest produce video images of your heart in motion. This test can help your doctor look at your heart’s structure and check it for any signs of infection or damage. Doctors may conduct another type of echocardiogram called a transesophogeal echocardiogram (TEE) to get a closer look at your heart valves. During this test, a small transducer attached to the end of a tube is inserted down the tube leading from your mouth to your stomach (esophagus). This test can allow your doctor to get much more detailed pictures of your heart than is possible with a transthoracic echocardiogram.
  • Electrocardiogram (ECG). While an ECG isn’t specifically used to diagnose endocarditis, it can show your doctor if something is affecting your heart’s electrical activity. During an ECG, sensors that can detect your heart’s electrical activity are attached to your chest, arms and legs. This test is used to measure the timing and duration of each electrical phase in your heartbeat.
  • Chest X-ray. X-ray images help your doctor see the condition of your lungs and heart. Your doctor can use X-ray images to see if endocarditis has caused your heart to enlarge or if any infection has spread to your lungs.
  • Computerized tomography (CT) scan or magnetic resonance imaging (MRI). You may need a CT scan or an MRI scan of your brain, chest or other parts of your body if your doctor thinks that infection has spread to these areas.

Endocarditis treatment

Many cases of endocarditis are successfully treated with antibiotics. Sometimes, surgery may be required to fix damaged heart valves and clean up any remaining signs of the infection.

Antibiotics

If you have endocarditis, your doctor might recommend high doses of intravenous (IV) antibiotics in the hospital. Your doctor will use blood culture tests to help identify the organism that’s causing your infection. Based on the results of your blood tests, your doctor will choose the most appropriate antibiotic or combination of antibiotics to fight the infection.

You’ll generally spend a week or more in the hospital when you start taking IV antibiotics. This gives your doctor time to see if the antibiotics are working against your infection. You’ll usually take antibiotics for several weeks to clear up the infection.

Once your fever and the worst of your signs and symptoms have passed, you might be able to leave the hospital and continue IV antibiotic therapy with visits to your doctor’s office or at home with home-based care. You’ll still need to see your doctor regularly to make sure your treatment is working.

It’s important to tell your doctor about any signs or symptoms that may mean your infection is getting worse, such as:

  • Fever
  • Chills
  • Headaches
  • Joint pain
  • Shortness of breath

Also, if you develop diarrhea, a rash, itching or joint pain, let your doctor know as soon as possible. These signs and symptoms may indicate you’re having a reaction to your prescribed antibiotic.

If you have shortness of breath or swelling in your legs, ankles or feet after you start antibiotic treatment, see your doctor immediately. These signs and symptoms can be indicators of heart failure.

Table 2. Pathogen-specific therapy of infective endocarditis

PathogenRegimen(s)Comments
Penicillin-susceptible (MIC ≤0.12 mcg per ml) viridans streptococci and S. bovisPenicillinAdverse effects include hypersensitivity and seizures
CeftriaxoneGenerally well tolerated, once daily administration may enable outpatient therapy
Penicillin (or ceftriaxone) + gentamicinAddition of an aminoglycoside enables a shorter treatment duration (2 weeks vs 4 weeks) at the expense of potential aminoglycoside adverse effects (renal, vestibular and cochlear toxicity)
VancomycinUse should be limited to those with true penicillin allergy
Penicillin-intermediate (MIC >0.12 and ≤0.5 mcg per ml) viridans streptococciPenicillin (or ceftriaxone) + gentamicin4 weeks of therapy recommended
VancomycinFor penicillin-allergic patients or to avoid gentamicin
Enterococci and penicillin-resistant (MIC >0.5 mcg per ml) viridans streptococciPenicillin (or ampicillin) + gentamicinExtended therapy (6 weeks) recommended for prosthetic valves and prolonged duration of symptoms prior to diagnosis
Ampicillin + ceftriaxoneFavoured in patients with renal insufficiency or high-level aminoglycoside resistance
Vancomycin + gentamicinNephrotoxic regimen; role of gentamicin is uncertain
DaptomycinFor vancomycin-resistant and penicillin-resistant enterococci; may combine with β-lactam
LinezolidMay be used for vancomycin- and penicillin-resistant enterococci, although adverse events including bone marrow suppression and neuropathy are of concern with extended treatment courses
StaphylococciNafcillinFor MSSA; adverse effects include rash, interstitial nephritis
CefazolinFor MSSA; better tolerated than nafcillin
VancomycinFor MRSA
Nafcillin + gentamicin2 week regimen for IV drug users with uncomplicated right-sided IE*
Nafcillin + gentamicin + rifampinFor prosthetic valve IE; substitute vancomycin for nafcillin in patients with MRSA
DaptomycinFDA-approved for right-sided S. aureus IE; observational data supports use in left-sided IE as well; may combine with β-lactam
HACEK strainsCeftriaxoneEffective for β-lactamase producing strains
Ampicillin/sulbactamFor β-lactamase producing strains
CiprofloxacinFor patients intolerant of β-lactam therapy
EnterobacteriaceaeExtended-spectrum penicillin or cephalosporin + aminoglycoside (or fluoroquinolone)Rare cause of IE and may require a tailored approach depending on the pathogen
Pseudomonas aeruginosaAn anti-pseudomonal β-lactam (such as ticarcillin, piperacillin, ceftazidime, cefepime or imipenem) + tobramycin (or fluoroquinolone)Typically requires prolonged therapy and valve surgery
FungiParenteral antifungal agent (most commonly an amphotericin product)Long-term suppressive therapy with an oral antifungal agent is often required

Notes:

*defined as infective endocarditis involving only the tricuspid valve, with no renal insufficiency and no extrapulmonary infection.

FDA, Food and Drug Administration; HACEK, Haemophilus species, Aggregatibacter species, Cardiobacterium hominis, Eikenella corrodens and Kingella species; IE, infective endocarditis; IV, intravenous; MIC, Minimum inhibitory concentration; MRSA, methicillin-resistant S. aureus; MSSA, methicillin-susceptible S. aureus.

[Source 28)]

Duration of antibiotic therapy

The duration of therapy must be sufficient to completely eradicate microorganisms within cardiac vegetations. Due to poor penetration of antibiotics into these vegetations and the slowly bactericidal properties of some of the commonly used drugs (such as vancomycin), extended courses of antibiotics are usually required. When bactericidal activity is rapid, shorter courses may be feasible. For example, combination therapy with penicillin or ceftriaxone and an aminoglycoside is synergistic for viridans-group streptococci-associated infective endocarditis, enabling effective courses as short as two weeks for susceptible strains 29). Right-sided vegetations tend to have lower bacterial densities and may also be amenable to shorter course therapy.

Duration of antimicrobial therapy is generally calculated from the first day on which blood cultures are negative. Blood cultures should be obtained every 24–72 hours until it is demonstrated that the bloodstream infection has cleared 30). If operative valve tissue cultures are positive, an entire antimicrobial course should be considered following cardiovascular surgery.

Surgery

If the infection damages your heart valves, you may have symptoms and complications for years after treatment. Sometimes surgery is needed to treat persistent infections or to replace a damaged valve. Surgery is also sometimes needed to treat endocarditis that’s caused by a fungal infection.

Depending on your condition, your doctor may recommend either repairing your damaged valve or replacing it with an artificial valve made of cow, pig or human heart tissue (biological tissue valve) or man-made materials (mechanical valve).

The three main surgical procedures that are used to treat endocarditis are:

  1. the repair of the damaged heart valve
  2. the replacement of the damaged heart valves with prosthetic ones
  3. the draining of any abscesses and the repair of any fistulas that may have developed in the heart muscle

Surgery for endocarditis can be very challenging, not least because a person who needs surgery will usually be very ill to begin with. Despite the best efforts of their surgical teams, approximately one in 10 people will die during or shortly after surgery for endocarditis.

The principal consensus indications for valve surgery are heart failure, uncontrolled infection and prevention of embolic events in patients at high risk 31). Uncontrolled infection may be related to paravalvular complications, such as abscess, an enlarging vegetation or dehiscence of a prosthetic valve. In addition, uncontrolled infection may be manifested by ongoing systemic illness with persistent fevers and positive blood cultures despite appropriate antibiotic therapy. As larger left-sided vegetations are more likely to lead to embolic events, infective endocarditis with a vegetation of >10 mm in length is a relative indication for surgical intervention.

The timing of cardiac surgery for patients with infective endocarditis and neurovascular complications remains controversial. A large prospective cohort study of 857 patients with infective endocarditis complicated by ischemic stroke without hemorrhagic conversion found that no patient benefit was gained from delaying surgery 32). By contrast, patients with embolic stroke complicated by hemorrhagic conversion sustained higher mortality when surgery was performed within 4 weeks of the hemorrhagic event compared with later surgery (75% versus 40%, respectively) 33). On the basis of these observational data, the American Heart Association 34) currently recommends that valve surgery may be considered in patients with infective endocarditis who also have stroke or subclinical cerebral emboli without delay if intracranial hemorrhage has been excluded by imaging studies and neurological damage is not severe (such as coma). In patients with major ischemic stroke or intracranial haemorrhage, American Heart Association guidelines currently state that delaying valve surgery for at least 4 weeks is reasonable 35).

Valve surgery was traditionally recommended for difficult-to-treat pathogens such as Pseudomonas aeruginosa, fungal organisms and β-lactam resistant staphylococci. However, these pathogen-specific recommendations for surgery have been recently called into question in favor of an individualized decision-making approach based upon hemodynamic and structural indications 36).

Other adjunctive therapies

Anticoagulation

Patients with prosthetic valve infective endocarditis who are receiving oral anticoagulants may be at an increased risk of death from cerebral hemorrhage 37). Antiplatelet therapies are not currently recommended for infective endocarditis. A single randomized trial examined the role of 325 mg of aspirin daily for patients with infective endocarditis. The incidence of embolic events was similar in between aspirin- and placebo-treated patients, and there was a non-significant increase in the rate of cerebral bleeding episodes 38). There are several limitations to this study, however, that include dose of aspirin used and delayed initiation of aspirin. For patients with another indication for antiplatelet therapy, it may be reasonable to continue the antiplatelet agent unless bleeding complications develop. Similarly, it is not recommended to initiate anticoagulant therapy such as warfarin for the purpose of treating infective endocarditis. In patients with infective endocarditis who have another indication for anticoagulation therapy, such as a mechanical valve, data are contradictory on whether to continue anticoagulation during acute therapy 39) and bridging therapy with heparin products has not been studied.

Management of metastatic foci

Metastatic foci of infection frequently complicate infective endocarditis. As with any infection, recognition of these foci of infection is important so that targeted interventions, such as drainage of abscesses or removal of infected prosthetic material, may be undertaken. This is of critical importance in patients who require valve surgery because a persistent source of infection may serve as a source from which a recently placed prosthetic valve or annuloplasty ring becomes infected 40). Some metastatic foci, such as vertebral osteomyelitis, may require additional antibiotic therapy beyond what is typically indicated for infective endocarditis 41). There is currently insufficient evidence to recommend specific imaging strategies to look for metastatic foci in all patients with infective endocarditis.

References   [ + ]