Recognition of infective endocarditis in the emergency department continues to be a challenge, as its signs and symptoms can be subtle, laboratory results are limited, and it can involve or lead to many other serious conditions. With the increase in use of medical access devices, implantable cardiac devices, and the rise of intravenous drug use, the epidemiology of infective endocarditis is changing. Diagnostic imaging has evolved, and the use of point-of-care ultrasound and transthoracic echocardiography are critical in making an early diagnosis. This review provides a best-evidence approach to diagnostic strategies, antibiotic recommendations, and surgical treatment recommendations for infective endocarditis.
A 25-year-old man presents to the ED with general malaise and fever for the preceding 3 weeks. He was seen recently at an outpatient clinic, diagnosed with pneumonia, and treated with azithromycin; however, he continues to have fevers. His history is remarkable for heroin addiction with recurrent treatment in rehabilitation over the past 3 years. He is ill-appearing, with a temperature of 39°C (102.2°F); heart rate, 120 beats/min; blood pressure, 100/60 mm Hg; respiratory rate, 26 breaths/min; and oxygen saturation of 90% on room air. He has diffuse crackles bilaterally; you do not auscultate any heart murmurs. Chest x-ray reveals the presence of multifocal infiltrates. Broad-spectrum antibiotics are administered, and the patient is admitted to the hospital with a diagnosis of multifocal pneumonia and sepsis. The more you contemplate the case, though, you wonder whether there is a diagnostic test that could have been done...
On a morning shift, a 55-year-old woman arrives in severe distress. Her husband informs you that she has had a decrease in energy over the past month and that her past medical history is notable for poorly controlled lupus and mitral valve prolapse. She was evaluated the week prior and discharged with a diagnosis of influenza. Her heart rate is 122 beats/min; blood pressure, 80/60 mm Hg; temperature, 38.0° (100.4°F); respiratory rate, 28 breaths/min; and oxygen saturation, 88% on room air. You auscultate crackles bilaterally and a loud holosystolic murmur most prominent at the cardiac apex. Chest x-ray reveals bilateral infiltrates. The patient improves initially with fluid resuscitation but rapidly decompensates, requiring intubation and vasopressor support. You administer 2 g of ceftriaxone IV and 1 g of vancomycin IV and admit her to the ICU for sepsis secondary to post–influenza pneumonia, but knowing that sepsis outcome is linked to administration of the correct antibiotic, you wonder whether there is a diagnostic test that would help in identifying the etiology...
A 62-year-old man presents to your ED complaining of oral pain. He has poor dentition and several past dental abscesses as well as a prosthetic aortic valve. Today, he presents with what appears to be a simple, superficial dental abscess that is amenable to drainage. Just as you are ready to incise and drain, you wonder whether you should give prophylactic antibiotics and, if so, which one...
Infective endocarditis (IE) can be difficult to diagnose in the emergency department (ED) because its signs and symptoms can represent many different and comorbid conditions. Although diagnostic and treatment therapies have advanced over the decades, the mortality rate has changed very little. The epidemiology of IE has changed greatly, however, due to evolving cultural, social, and technological factors, and it is essential to be aware of these factors in order to prevent, recognize, and treat this disease.1 Not only are there diagnostic difficulties associated with identification of patients with IE, but there is debate over the best courses of treatment and when to advance to more aggressive therapies. In addition, treatment presents a variety of social challenges, as the burden of injection drug use increases in the United States.
There have been recent guideline changes and technical advances in identification and management of IE. Epidemiologic studies of the effects of recently implemented recommendations have been carried out, and the results are presented here. Key presentations and risk factors for IE are discussed, to help in the clinical decision-making needed to maximize outcomes for patients with IE. This issue of Emergency Medicine Practice reviews the best available evidence regarding the diagnosis and treatment of patients with IE, and provides evidence-based recommendations for treatment.
PubMed and MEDLINE®, Google Scholar, and the Cochrane Database of Systematic Reviews were searched for literature published from 2009 to 2020, using specific search terms: infective endocarditis, infectious endocarditis, culture negative endocarditis, bacterial endocarditis, valvular infection, infective endocarditis in injection drug users, and cardiac device infections. Because the disease carries a high risk of morbidity and mortality and affects a broad demographic, there is abundant literature available, as well as many articles discussing the controversies associated with management strategies. Extrapolation of data was limited to meta-analyses, systematic reviews, well-designed clinical trials, large observational studies, and clinical guidelines. Case series and case reports were included only when trends were seen across the literature for specific organisms or populations.
In all, 94 articles were identified, including multiple medical, surgical, and several combined society guidelines. Challenges in the search and assimilation of data included the broad scope of literature, with many publications geared toward inpatient management of already-diagnosed disease and not specifically toward acute management and diagnosis.
First described in 1646 by Lazar Riviere, IE remains an elusive and deadly disease. Although IE has classically been associated with malformed or damaged heart valves that have been seeded by bacteria (most commonly, streptococci), the increasing burden of intravenous (IV) drug use as well as the use of implantable cardiac devices and medical venous access devices have changed the disease’s etiology and epidemiology. Historically, specific entities of acute and subacute bacterial endocarditis were defined, but it has been recognized that the site of infection (right vs left) and type of bacteria involved are more important factors in classification and management.
More than 70% of IE cases occur in native valves that are either damaged or possess altered flow dynamics that predispose the patient to platelet aggregation. In native valves, mitral valve prolapse is the most common risk factor for IE, and it raises the risk of IE by 8-fold. In the subpopulation of patients with IV drug use, impurities in an injectable drug contribute to valvular damage through micro-trauma that serves as a nidus for infection. Regardless of the initiating factor, platelets provide a surface for bacterial adherence and synergistically act to shelter anchored bacteria from immune mechanisms.2
While often considered a rare disease, with a global incidence of between 1.5 and 11.6 cases per 100,000 people, bias toward the developed world in the literature likely underestimates the worldwide disease burden and mortality.3 The association of IE with rheumatic heart disease is no longer the case in developed countries, where most cases are related to either valvular degeneration, IV drug use, or nosocomial infection.4 Due to the increased use of invasive intravenous access medical devices, today the mean age of an IE patient is older than 50 years, whereas a century ago, the mean age was under 30 years.5 Currently, hospitalization or recent hospital exposure is associated with 25% of cases of IE.5
In a 2013 systematic review of global trends in IE epidemiology over the last 50 years, the percentage of staphylococcal endocarditis had increased significantly, with this organism outpacing viridans group streptococci as the leading cause of endocarditis in the United States. Cases of enterococcal and coagulase-negative staphylococcal (CoNS) endocarditis have also increased over time, and are fast approaching that of viridans group streptococci IE.6 (See Figure 1.)
These trends are most evident in North America, where the opioid abuse epidemic has led to an increase in native valve endocarditis caused by Staphylococcus aureus. Currently, 75% of cases of IE are native valve endocarditis, with 80% of all cases involving either the mitral or aortic valves.7 In cases of IE in IV drug users, most lesions are located on the tricuspid valve, leading to few systemic manifestations. Cases of native valve endocarditis due to CoNS approximate 8% to 10%, and about half of these cases are healthcare related. Despite differences in virulence, large studies show similar mortality in IE patients infected with S aureus and CoNS.8
In addition to risk factors already discussed for IE in general, patients who are immunocompromised, elderly, have had abdominal or genitourinary instrumentation, or prosthetic heart valves seem to be at the highest risk for contracting enterococcal IE.9 (See Table 1.) S aureus bacteremia alone is likely an independent risk factor for IE development. In a 2014 systematic review of 3513 patients with S aureus bacteremia, transesophageal echocardiography (TEE) demonstrated that between 14% and 28% of those with bacteremia actually had IE; however, this review may be biased, in that it included only prospective observational studies, and it is likely that clinician suspicion for IE influenced referral for TEE.10 More-recent reviews reinforce that TEE is useful in undifferentiated or complicated S aureus bacteremia; however, there is a low-risk group of patients who are less likely to benefit from TEE.11 This group includes patients without indwelling lines, patients without cardiac devices or valvular disease, and those with brief bacteremic episodes (< 48 hours duration). If bacteremia persists for more than 3 days, it would be appropriate to consider TEE. If the TEE is negative, it is prudent to repeat the TEE in 2 days if the patient is still febrile and without a source, given that TEE does have a small (but not insignificant) false-negative rate.
One notable type of CoNS leading to IE is Staphylococcus lugdunensis (SLuG). SLuG behaves much like methicillin-resistant Staphylococcus aureus (MRSA), with an aggressive course and a propensity to cause perivalvular abscess. Detection of SLuG in a single blood culture indicates IE in approximately 16% of patients, and in 25% of patients with 2 positive cultures. Thus, SLuG should be considered as a cause of IE, especially in a patient with CoNS in peripheral blood cultures and fever without a source. Despite its MRSA-like behavior, SLuG is sensitive to beta-lactam antibiotics.12
Other risk factors for IE include subaortic valvular stenosis, ventricular septal defects, pulmonic stenosis, tetralogy of Fallot, and other congenital heart lesions. The risk of IE in adults with congenital heart disease is approximately 1% and is lesion-dependent, with patients having patent ductus arteriosus having the lowest risk.13 In children, however, approximately half of all IE cases are related to congenital heart disease.14
Historical mortality in cases of IE approximates 30%, according to several different analyses. Recent meta-analysis data indicate that although diagnostics and therapeutics have changed, mortality has not been significantly impacted. In a meta-analysis of worldwide outcomes including 22,382 patients, short-term 30-day all-cause mortality for IE was 20%, while long-term post discharge mortality rates approached 37%.15 In the United States, 90-day mortality rates are approximately 24%.15,16 Global and regional mortality differences are multifactorial and stem from a combination of healthcare disparities, differences in patient risk factors, valvular involvement, and bacterial virulence.
Many of the differential diagnoses for IE may present with IE and lead to IE’s reputation as the “great imitator.” Differential diagnoses include pneumonia, sepsis, acute heart failure, acute ischemic stroke, intracranial hemorrhage, meningitis, acute kidney injury, and dysrhythmias, among others. IE may involve or lead to any of these conditions, and the key is for the emergency clinician to consider IE when caring for critically ill patients with multisystem involvement.
1. “I figured the persistent fever was just viral; she looked so well.”
Failing to consider IE in a patient with fever without a source, even if the patient appears well, can lead to missed diagnoses. Often, suspicion of IE is the most difficult part of the workup, and can add significantly to the diagnostic momentum if it is suspected.
2. “My 32-year-old patient had developed acute heart failure, but I assumed it was because he has diabetes and is on hemodialysis.”
Consider IE in any young patient with new-onset acute heart failure, which suggests perivalvular abscess. Other clinical syndromes in young patients that can indicate IE are stroke or multifocal pneumonia, both of which are suggestive of embolic phenomena.
6. “A TTE was negative in the ED, so I assumed that the patient didn’t have IE.”
Imaging modalities such as TTE and POCUS are most useful as rule-in, not rule-out tests. Even if a TEE is negative, in the presence of high suspicion, it should be repeated within a short interval, as it is only 90% sensitive and can miss small lesions, especially right-sided lesions.
Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.
To help the reader judge the strength of each reference, pertinent information about the study, such as the type of study and the number of patients in the study is included in bold type following the references, where available. In addition, the most informative references cited in this paper, as determined by the author, are highlighted.
Dr. Ashoo is a practicing emergency physician, board-certified in emergency medicine and clinical informatics. Join him as he takes you through the September 2020 issue of Emergency Medicine Practice: Infective Endocarditis: Identification and Management in the Emergency Department (Infectious Disease CME)
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The Duke Criteria tool provides formal criteria for diagnosing and stratifying patients suspected of having infective endocarditis (IE) into “definite,” “possible,” and “rejected” groups. The criteria should be applied to patients for whom there is a high clinical suspicion of IE.
Patients with IE have a wide range of clinical features, and diagnosing IE is challenging. The Duke Criteria tool is sensitive for disease detection and has a high negative predictive value. Negative blood cultures may be confounded by a recent history of treatment with antibiotics. Clinicians should suspect IE and consider using the Duke Criteria in patients with: prolonged fever (fever of unknown origin); fever with vascular phenomena (stroke, limb ischemia, physical findings of septic emboli); persistently positive blood cultures (2 or more); patients who have prosthetic valves and are febrile; injection drug users who are febrile; patients who have a predisposing heart condition and are febrile; or patients who have a recent history of hospitalization and are febrile. An IE diagnosis must be made as soon as possible to initiate therapy. If a patient is determined to be in the "definite" group by the Duke Criteria, antibiotic treatment should be started based on guidelines and microbiology, and candidates who need surgical treatment should be identified.
For patients in the "possible" group, clinical judgment should be used to decide whether the patient has IE. For patients in this group, trans-esophageal echocardiography can be considered, if not already done; candidates for surgical treatment should be identified; patients should be regularly watched for major or minor signs of IE and examined for physical findings suggestive of IE (Roth spots, Osler nodes, Janeway lesions); and blood cultures should be drawn regularly (if not positive earlier) to look for microbiologic evidence. If patients are in the “rejected” group, other causes of fever should be considered, such as other infectious sources and rheumatologic or oncologic causes.
If clinical suspicion for IE is high and the patient is in the "possible" group, transesophageal echocardiography should be considered. IE should be considered, if not previously suspected, if the patient has persistently positive (2 or more) blood cultures. For patients who have subacute IE and are hemodynamically stable, empiric antibiotics can be avoided so that additional blood cultures can be obtained without the confounding effect of empiric treatment.
Pranay Aryal, MD
In the original study by Durack et al, 405 consecutive cases of suspected IE in 353 patients were evaluated in a tertiary hospital from 1985 to 1992.
The Duke Criteria improved upon the older von Reyn criteria. Eighty percent of the 69 pathologically confirmed cases were classified as clinically definite endocarditis by Duke Criteria, whereas the von Reyn criteria classified only 35 (51%) of the pathology-confirmed cases into the probable category
(P < .0001). Twelve (17%) of the pathology-confirmed cases were rejected by the von Reyn criteria, but none were rejected by the Duke Criteria.
Among the 150 cases rejected by von Reyn criteria, 11 were definite, 87 were probable, and 52 were rejected by the Duke Criteria.
The Duke Criteria tool was validated during the late 1990s with 11 major studies, which included 1700 geographically and clinically diverse patient groups (adult, pediatric, and geriatric patients; patients from the community; patients with and without injection drug use; patients with both native and prosthetic valves; and patients treated outside of the United States). It showed high sensitivity (> 80%) and a high negative predictive value in these studies.
David Durack, MD
The infective endocarditis (IE) mortality score provides an objective 6-month mortality estimate in patients with confirmed IE. IE has an overall 6-month mortality of approximately 25% in all patients. Older age and history of dialysis are the highest risk factors. IE complications also suggest a high mortality. Surgery is associated with a lower mortality rate but is infrequent in high-risk patients. Mortality ranges from 10% in the lowest-risk quintile to 53% in the highest-risk quintile.
Patients with IE may benefit from consultation with cardiothoracic surgery and infectious disease services. It is important to note that surgery in the Park 2016 study was associated with lower mortality, but the highest-risk patients were less likely to receive surgery, probably because they were high-risk surgical patients as well. This study was performed in referral centers experienced with endocarditis and cardiac surgery (likely tertiary and quaternary academic centers).
Graham Walker, MD
The c-statistics for the derivation and validation models are 0.715 and 0.682, respectively. The derivation cohort contained 4049 patients, and the validation cohort included 1197 subjects.
Andrew Wang, MD
Park LP, Chu VH, Peterson G, et al. Validated risk score for predicting 6-month mortality in infective endocarditis. J Am Heart Assoc. 201618;5(4):e003016.
Anthony J. Hackett, DO, FAAEM, FACEP; Jonathan Stuart, DO, MS
Katrina Harper-Kirksey, MD; Evan Leibner, MD, PhD
September 1, 2020
October 1, 2023
4 AMA PRA Category 1 Credits™, 4 ACEP Category I Credits, 4 AAFP Prescribed Credits, 4 AOA Category 2-A or 2-B Credits. Specialty CME Credits: Included as part of the 4 credits, this CME activity is eligible for 2 Infectious Disease CME credits
Date of Original Release: September 1, 2020. Date of most recent review: August 10, 2020. Termination date: September 1, 2023.
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Specialty CME: Included as part of the 4 credits, this CME activity is eligible for 2 Infectious Disease CME credits.
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