Abstract
Infectious endocarditis (IE) is an inflammatory condition that affects the endocardium, the heart's inner lining, as well as the valves that separate each of the heart's four chambers. Despite a low prevalence and improvements in its management, IE remains associated with a high burden of morbidity and mortality. IE can be associated with reduced quality of life and a high risk of re-infection. It often requires prolonged intravenous antibiotic treatment. The mortality rate is high, with an estimated one-third of patients dying within a year of diagnosis. It is important to have an awareness of the key features of a patient’s history and examination findings that should prompt referral to specialist services.
Clinical care scenario 1.
A 75-year-old male was brought into the surgery by his daughter. His primary complaint was an altered mental state with new symptoms of chest discomfort, lethargy chills and fever. His medical record showed he had a prosthetic heart valve operation a few years ago. Bedside examination revealed a mildly raised temperature with increased heart rate, increased respiratory rate and new onset cardiac murmur. The patient was sent to the hospital as a matter of urgency for likely sepsis-related symptoms. Eventually, after investigations in secondary care, including blood cultures and echocardiography, a diagnosis of IE was made. He was treated medically with antibiotics and given further follow-up to consider potential surgery.
Epidemiology
The incidence of IE varies between countries with an estimated three to ten episodes per 100 000 person-years and a peak incidence of 14.5 episodes per 100 000 person-years in patients aged 70–80. There is a male-to-female ratio of nearly 2:1 (Habib et al., 2009). Over the last 5 years, the incidence of IE among the population has changed. IE was typically a disease of young or middle-aged adults with underlying rheumatic heart disease, congenitally abnormal valves or congenital heart disease (CHD). Nowadays, following the decline in the aforementioned diseases and with the development of antibiotics, the main risk factors for IE are regular IV access, such as haemodialysis and IV drug abuse, and those with indwelling intra-vascular devices, including central venous lines, and artificial heart valves (Ambrosioni et al., 2017) (Box 1). Predisposing risk factors for endocarditis.
• Aortic valve disease • Mitral valve prolapse • Rheumatic valve disease • Congenital heart disease • Prior infective endocarditis • Prosthetic heart valves • Patients with implanted cardiac devices (permanent pacemakers/implantable cardioverter-defibrillator)
• Chronic kidney disease (particularly in haemodialysis patients) • Chronic liver disease • Malignancy • Poorly controlled diabetes • Poor dentition or dental procedure • Immunocompromised state (including HIV infection).
• Advanced age • Male gender • Intravenous drug use • Corticosteroid use • Indwelling line for venous access
Aetiology
Staphylococcus aureus is the leading cause of IE worldwide, with its prevalence increasing in many parts of the world (Barnett, 2016): 80% of IE cases are caused by either staphylococci or streptococci. S. aureus is responsible for 25–30% of IE cases, whereas coagulase-negative staphylococci are responsible for 11% of IE cases. Streptococci, on the other hand, are responsible for 30% of cases and enterococci are responsible for 10% of cases. There are also non-bacterial causes of IE, such as viruses and fungi and non-infective causes of endocarditis, which are mostly related to systemic diseases such as systemic lupus erythematosus or Bechet’s disease (Bussani et al., 2019).
Clinical suspicion
The complexity of IE and the subtly of its presentation make it difficult to diagnose. The clinical history can be variable, and classically described signs and/or symptoms are not always present. Clinicians should consider this diagnosis in any patient with predisposing risk factors who present with fever or sepsis of unknown origin.
Acute IE vs subacute IE
The acute form of IE usually manifests as a rapidly progressing disease characterized by fever (90% of all patients), rigors and sepsis (extreme body temperatures, low blood pressure, confusion and reduced levels of consciousness, increased heart rate, rash and reduced urine output). Conversely, subacute IE is frequently misdiagnosed and manifests over several weeks to months, with nonspecific symptoms such as the insidious onset of fever, chills, malaise, fatigue, weight and appetite loss, and new heart murmur. Heart murmurs are found in up to 85% of patients with subacute IE, and approximately 25% of patients have embolic complications at the time of diagnosis in the brain, lungs or spleen. Embolic complications may manifest as stroke, haemoptysis or left upper quadrant abdominal pain due to splenic infarction.
Patients with subacute IE are often missed due to the high index of suspicion required to formulate a diagnosis. Hence, IE should be suspected in any patient presenting with fever and embolic phenomena (Mudroch, 2009). Although uncommon as patients usually present earlier, splinter haemorrhages, Osler nodes (painful lesions on the hands and feet), Roth spots (white-centred retinal haemorrhage), Janeway lesions (nontender haemorrhagic lesions on the hands and feet) and glomerulonephritis can still be seen in IE patients.
Diagnosis
The modified Duke criteria (Box 2) provide a framework for diagnosis of endocarditis and rely on the detection of infecting microorganisms in addition to echocardiographic and clinical findings. It is crucial to obtain a rapid and accurate diagnosis of suspected IE since a delay in reaching a diagnosis and initiation of treatment can lead to more complications and poorer outcomes (Habib et al., 2015). Modified Duke criteria for diagnosis of infective endocarditis.(Definite IE: Two major, Or one major and three minors, Or five minors. Possible IE = one major and one minor, or three minor).
1. Two separate blood cultures showing consistent IE microorganisms: ○ S. aureus, streptococci viridans, Streptococcus bovis, HACEK group; OR ○ Community-acquired enterococci within the absence of a primary focus; OR Persistent positive blood cultures showing microorganisms in line with IE: ○ Two or more positive cultures taken more than 12 hours in between; OR ○ Three or a majority of four or more separate blood cultures (at least 1 hour between the initial and last sample); OR ○ Single positive blood culture for Coxiella burnetii or antiphase I IgG antibody titre >1:800 2. Positive ECHO finding in line with IE plus: ○ Vegetation; OR ○ Abscess; OR ○ New partial dehiscence of prosthetic valve 3.
1. Temperature >38°C 2. Pre-existing heart disease or IV drug use 3. Vascular: Arterial emboli, splenic infarction, mycotic aneurysms, intracranial haemorrhage or Janeway lesions 4. Immunology: Glomerulonephritis, Osler’s nodes, Roth’s spots or rheumatoid factor 5. Microbiology: Positive blood culture but does not match the primary major criteria listed above or positive serology results indicating infection with IE consistent microorganism
Microbiological
Identification of the specific microbial organism responsible for a patient’s IE is important to be able to provide optimal care. Initially, broad-spectrum antibiotic therapy will be required until it can be further tailored based on cultures. To ascertain the responsible organism, multiple blood cultures are required as many organisms can be difficult to culture. Approximately 85% of all cases have positive cultures; however, up to 15% of patients can have negative blood cultures. This typically results from prior antibiotic therapy or infection by other organisms (Gould et al., 2012). After 48 to 72 hours, if results are negative and the clinical suspicion of IE is still strong, additional blood cultures and serological testing should be considered in the hospital, following a consultation with an infectious disease specialist and a microbiologist (Mudroch, 2009).
Diagnostic imaging
The European Society of Cardiology (ESC) recommends the use of the non-invasive transthoracic echocardiogram (TTE) in any patient suspected of having native valve IE. The sensitivity of TTE in detecting vegetations upon native valves is estimated at 70%, with published figures ranging from 51% to 80%. This is reduced to 50% or lower in patients with prosthetic valves or implanted cardiac devices. Transoesophageal echocardiography (TOE), with 90% sensitivity, is, therefore, indicated in patients with prosthetic valves and no contraindications to the test. Otherwise, it should be done after TTE if the results of TTE are negative, but the clinical suspicion for infective endocarditis remains high (Mgbojikwe et al., 2019). The TOE is not recommended for all patients due to the invasive nature of the endoscopic procedure.
Management
Antimicrobial treatment
Initiation of antibiotic therapy is the most important step in treating IE. It is crucial to begin empirical antibiotic treatment while awaiting the findings of the initial blood cultures. Once culture and sensitivity findings are available, the antibiotic regimen is tailored accordingly. Long-term therapies are frequently advised; typically, 4 weeks for native valve endocarditis and 6 weeks for prosthetic valve endocarditis and should be counted from the first day of negative blood cultures. Ideally, IE should be managed by a multi-disciplinary team of cardiologists, infectious disease experts and microbiologists (Habib et al., 2015).
Outpatient parenteral antibiotic therapy (OPAT) is considered in patients with native valve endocarditis who are highly responsive to treatment and experience no complications after treatment. It has been shown to be efficient and cost effective in the treatment of endocarditis. Inpatient treatment is usually recommended during the first 2 weeks of antibiotic therapy as there is a higher risk of complications. OPAT should only be performed with appropriate patient education, regular post-discharge follow-up and continuous medical input.
Complications of endocarditis and indications for surgery
Up to 50% of patients will require surgery for IE. Correct planning of the timing and implementation of surgical approaches is essential, particularly for cases with complications (Mudroch, 2009).
The principal indications for surgery are:
Heart failure (HF): HF is the most prevalent and severe complication of IE; the presence of HF is an indication for early surgery in both native and prosthetic valve IE, even in patients with cardiogenic shock and severe valve disease Failure to control infection: Uncontrolled ongoing local infection, ‘difficult-to-treat’ organisms or persistence of positive blood cultures despite appropriate antibiotics Prevention of septic emboli: Embolism is very frequent in IE, complicating 20–50% of cases of IE, reducing risk after initiation of antibiotic therapy. It is related to the size and the mobility of the vegetation, although other risk factors may exist: vegetation >30 mm vegetation >10 mm with an embolic event while on appropriate antibiotic therapy vegetation >10 mm and severe native or prosthetic valve disease and the patient is at low operative risk. (Habib et al., 2015).
Prophylaxis
In 2008, the National Institute for Health and Care Excellence (NICE) recommended that antibiotic prophylaxis (AP) no longer be used due to the lack of strong evidence for its efficacy and expressed concerns about potential side effects, the potential development of antibiotics resistance and the cost (Box 3). Until this point, AP was widely used for moderate and high-risk patients, for example patients with valve replacement undergoing dental surgery. Of note, the ESC guidelines for the management of IE (Habib et al., 2015) still recommend AP for high-risk patients. NICE guidelines for antibiotic prophylaxis for endocarditis.
Healthcare practitioners should consistently educate patients, especially those who are at risk of developing IE, about the following: • Explain to patients why the risk of AP might overweigh the benefits, the reason why not routinely recommended • Keep good oral health and oral hygiene • Signs and symptoms of IE and when to consider seeing a doctor • The importance of understanding the risks of body piercing or tattooing
Antibiotic prophylaxis is not recommended for patients undergoing dental procedures, including chlorhexidine mouthwash, use should not be prescribed even for high-risk patients Also, AP is not routinely indicated in other non-dental procedures including: • Upper and lower gastrointestinal tract • Upper and lower respiratory tract • Genitourinary tract.
• To decrease the chance of developing IE, all episodes of infection must be investigated and treated promptly • A person at risk of IE should be offered an antibiotic effective against IE-causing organisms, particularly if they are receiving antimicrobial therapy that is due to a gastrointestinal or genitourinary surgery done at a site of suspected infection Source: NICE, 2008.
Key points
Infective endocarditis is a life-threatening condition; although rare, it carries significant morbidity and mortality
Epidemiology for IE has changed and elderly people with prosthetic heart valves, haemodialysis, venous catheters, immunosuppression and intravenous drug use are at increased risk of IE
Ninety per cent of patients present with fever; other symptoms include sweating, chills, weight loss, anorexia and heart murmur
In primary care, a diagnosis of IE can be suspected based on clinical symptoms including fever, murmur, symptoms related to emboli and an abnormal urine dip in an at-risk patient; the modified Duke criteria are used to help establish a diagnosis of endocarditis in secondary care
Intravenous antibiotics treatment is the first-line treatment for bacterial IE; the indication of surgery will greatly depend on whether complications are present
The NICE guidelines do not recommend routine use of prophylactic antibiotics due to lack of evidence and concerns about antimicrobial resistance and side-effects
