Diagnosis, Antimicrobial Therapy, and Management of Complications: A Statement for Healthcare Professionals From the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association—Executive Summary: Endorsed by the Infectious Diseases Society of America
Background— Despite advances in medical, surgical, and critical care interventions, infective endocarditis remains a disease that is associated with considerable morbidity and mortality. The continuing evolution of antimicrobial resistance among common pathogens that cause infective endocarditis creates additional therapeutic issues for physicians to manage in this potentially life-threatening illness.
Methods and Results— This work represents the third iteration of an infective endocarditis “treatment” document developed by the American Heart Association under the auspices of the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease of the Young. It updates recommendations for diagnosis, treatment, and management of complications of infective endocarditis. A multidisciplinary committee of experts drafted this document to assist physicians in the evolving care of patients with infective endocarditis in the new millennium. This executive summary addresses the major points detailed in the larger document that contains more extensive background information and pertinent references. For the first time, an evidence-based scoring system that is used by the American College of Cardiology and the American Heart Association was applied to treatment recommendations. Tables also have been included that provide input on the use of echocardiography during diagnosis and treatment of infective endocarditis, evaluation and treatment of culture-negative endocarditis, and short-term and long-term management of patients during and after completion of antimicrobial treatment. To assist physicians who care for children, pediatric dosing was added to each treatment regimen.
Conclusions— The recommendations outlined in this summary should assist physicians in all aspects of patient care in the diagnosis, medical and surgical treatment, and follow-up of infective endocarditis, as well as management of associated complications. Clinical variability and complexity in infective endocarditis, however, dictate that these guidelines be used to support and not supplant physician-directed decisions in individual patient management.
This statement updates and revises recommendations for the diagnosis and management of infective endocarditis (IE) published by the American Heart Association Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease in 1995. In addition, it updates and incorporates recommendations for the management of complications in IE published by the same committee in 1998. (These recommendations are available in their entirety at http://www.americanheart.org/presenter.jhtml?identifier=3004539.) The present Writing Committee conducted a comprehensive review of the literature published between 1990 and 2004 to assist the group in updating the previous versions of the guidelines. Literature searches of the PubMed/MEDLINE databases were undertaken to identify pertinent articles. Searches were limited to the English language. The major search terms included endocarditis, infective endocarditis, infectious endocarditis, intracardiac, valvular, mural, infection, diagnosis, bacteremia, case definition, epidemiology, risks, demographics, injection drug use, echocardiography, microbiology, culture-negative, therapy, antibiotic, antifungal, antimicrobial, antimicrobial resistance, adverse drug effects, drug monitoring, outcome, meta-analysis, complications, abscess, congestive heart failure, emboli, stroke, conduction abnormalities, survival, pathogens, organisms, treatment, surgery, indications, valve replacement, valve repair, ambulatory care, trials, and prevention.
This Executive Summary highlights some of the important clinical issues in the diagnosis and management of IE. All of these issues are addressed more fully in the Web-based complete statement. The Executive Summary includes summary comments and detailed tables that focus on key aspects of patient management. A list of references is provided in the full statement.
Evidence-Based Scoring System
This is the first time that the American College of Cardiology/American Heart Association evidence-based scoring system (see http://circ.ahajournals.org/manual/manual_IIstep6.shtml) has been incorporated into the American Heart Association’s endocarditis treatment guidelines. The purpose of the scoring system is to assist the clinician in interpreting these recommendations and formulating treatment decisions. The system is based on both a classification of recommendations and the level of evidence. Each treatment recommendation has been assigned a class and a level of evidence. The use of this system should support but not supplant the clinician’s decision-making in the management of individual patients’ cases.
Classification of Recommendations
Class I: Conditions for which there is evidence, general agreement, or both that a given procedure or treatment is useful and effective.
Class II: Conditions for which there is conflicting evidence, a divergence of opinion, or both about the usefulness/efficacy of a procedure or treatment.
Class IIa: Weight of evidence/opinion is in favor of usefulness/efficacy.
Class IIb: Usefulness/efficacy is less well established by evidence/opinion.
Class III: Conditions for which there is evidence, general agreement, or both that the procedure/treatment is not useful/effective and in some cases may be harmful.
Level of Evidence
Level of Evidence A: Data derived from multiple randomized clinical trials
Level of Evidence B: Data derived from a single randomized trial or nonrandomized studies
Level of Evidence C: Consensus opinion of experts
Although initially established to more accurately define cases of IE for epidemiological studies and clinical trials, the Duke criteria have been used extensively during the past decade to assist clinicians in the diagnosis of IE. The 2 key components of the criteria are persistent bacteremia resulting from typical IE organisms and evidence of cardiac valvular involvement (eg, vegetation, new murmur of valvular regurgitation, paravalvular abscess). Supporting findings include fever, risk factors for IE, vascular or immune complex phenomena, and intermittent bacteremia or fungemia.
Transesophageal echocardiography is the preferred imaging technique for the diagnosis and management of IE in adults with either high risk for IE or moderate to high clinical suspicion of IE or in patients in whom imaging by transthoracic echocardiography is difficult (Figure). Transesophageal echocardiography is more sensitive than transthoracic echocardiography for detecting vegetations and cardiac abscess. Recommendations for the timing of echocardiography in diagnosis and management of IE are presented in Table 1. The echocardiographic features that suggest the potential need for surgical intervention are listed in Table 2.
Recommended antibiotic treatment regimens for IE are described in Tables 3 through 13⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓, including drug dose, dosing frequency, route(s) of administration, duration of therapy, and strength of recommendation. Tables 3 through 5⇓⇓ provide regimens for IE caused by viridans group streptococci and Streptococcus bovis; Tables 6 and 7⇓, staphylococci; Tables 8 through 11⇓⇓⇓, enterococci; Table 12, HACEK microorganisms; and Table 13, culture-negative IE, including Bartonella endocarditis. With few exceptions, antibiotic treatment is prolonged, bactericidal, administered parenterally, and given in high dosages. Because complications of IE are frequent and the antimicrobial agents used to treat IE may be associated with adverse effects, patients must be monitored closely by an experienced team of clinicians.
A dramatic increase in resistance to antibiotics among the most common causes of IE is a major reason for updating these recommendations. Multidrug resistance is now commonly described among isolates of streptococcal, staphylococcal, and enterococcal species that cause IE. In addition, many of the Gram-negative bacteria that cause IE have become more drug resistant. Increasing drug resistance has occurred among “community-acquired” isolates such as HACEK (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, and Kingella) microorganisms, Salmonella species, and Enterobacteriaceae, as well as among nosocomial isolates such as Pseudomonas species. More data are needed to define the optimal treatment regimens for IE caused by multidrug-resistant Streptococcus pneumoniae, vancomycin-resistant strains of Enterococcus faecium, and multidrug-resistant Staphylococcus aureus. In addition, new information has prompted a reexamination of recommendations for the duration of therapy for IE. For example, data from Sweden suggest that in combination with a cell wall–active antibiotic for treatment of IE resulting from enterococci, the duration of aminoglycoside administration may be limited to only the first 2 weeks rather than the entire 4 to 6 weeks of therapy with a cell wall–active agent and no decrease in cure rates.
Despite advances in diagnostic techniques, (blood) culture–negative endocarditis remains a clinical conundrum among IE cases. Patients with culture-negative endocarditis can be divided into 2 categories: those with negative blood cultures associated with recent antibiotic therapy and those infected with microorganisms that are difficult to grow in routinely used blood culture media. The epidemiological clues listed in Table 14 may be helpful for determining the most appropriate antibiotic regimen for the individual patient with culture-negative endocarditis.
There is much room for improvement in the treatment of fungal IE. The mortality rate remains unacceptably high, particularly for IE associated with molds, and new treatment strategies are still under investigation. Many experts advocate treatment of fungal IE that involves both medical and surgical intervention in most cases. More recently, long-term suppressive therapy, usually with an oral azole agent, has been adopted for some patients who survive acute medical and surgical therapies to prevent relapse of fungal IE. Suppressive therapy also has been used for patients who are too ill to undergo valve replacement but who have responded to acute antifungal treatment.
Complications of IE
Among the complications of IE, congestive heart failure (CHF) has the greatest impact on prognosis. CHF in IE, regardless of its cause, is associated with a grave prognosis with medical therapy alone and is the most powerful predictor of a poor outcome with surgical therapy as well. In any patient with IE and CHF, the decision to delay surgery to extend the duration of preoperative antibiotic therapy carries with it the risk of permanent ventricular dysfunction and should be discouraged. Echocardiographic evaluation helps to delineate the causes and severity of CHF.
The rate of embolic events drops dramatically during and after the first 2 to 3 weeks of successful antimicrobial therapy. The role of echocardiography in predicting embolic events has been controversial. The role of surgical intervention to prevent systemic embolization must be considered in the context of the specific patient, with the greatest benefit in the early phase of IE, when embolic rates are highest and other predictors of a complicated course (eg, recurrent embolization, CHF, aggressive antibiotic-resistant organisms, prosthetic valve IE) are present (see Table 2).
In patients with Staphylococcus aureus prosthetic valve IE who have experienced a recent central nervous system embolic event, discontinuation of all anticoagulation for at least the first 2 weeks of antibiotic therapy is generally advised. In addition, the routine use of aspirin or other drugs that interfere with platelet function for established IE is not recommended.
Extension of IE beyond the valve annulus is associated with a higher mortality rate, CHF, and the need for surgical intervention. Surgery for perivalvular extension of IE is aimed at eradicating infection as well as correcting hemodynamic abnormalities.
Splenic abscess and bland infarctions both are complications of IE, and differentiating one from the other may be difficult. On CT, splenic abscess is frequently seen as a single or multiple contrast-enhancing cystic lesions, whereas infarctions (single or multiple) typically are peripheral, low-density, wedge-shaped areas. Infarctions are generally associated with clinical and radiological improvement during appropriate antimicrobial therapy. In contrast, persistent or enlarged splenic defects on CT or MRI, ongoing sepsis, and recurrent positive blood cultures suggest splenic abscess, which may respond poorly to antimicrobial therapy alone. Definitive treatment in such cases is splenectomy with appropriate antimicrobial therapy.
Mycotic aneurysms (MAs) caused by IE occur most frequently in the intracranial arteries, followed by the visceral arteries and the arteries of the upper and lower extremities. The overall mortality rate among patients with IE and intracranial MAs may be as high as 60%. For patients with unruptured intracranial MAs, the mortality rate is ≈30%, but with ruptured MAs, the mortality rate approaches 80%. Conventional cerebral angiography remains the optimal imaging test for diagnosing intracranial MAs. There is no accurate way of identifying patients at risk for “imminent rupture” of an intracranial MA, and decisions about the use of surgical intervention in addition to medical therapy must be individualized. Endovascular treatment of intracranial MAs has been used as an alternative to surgical clipping or ligation. Because it is less invasive than traditional surgical approaches, endovascular therapy may be preferred for patients who are poor candidates for traditional surgical intervention.
Most extracranial MAs will rupture if not excised; therefore, surgical intervention is necessary for cure of extracranial MA and survival for most of these patients.
Care During and After Completion of Antimicrobial Treatment
Care is divided temporally into 3 phases that are highlighted in Table 15. The recommendations (Class IIb; Level of Evidence: C) focus on the importance of prompt identification of either relapse or recurrence of IE. Patients who have had previous episodes of IE and patients with prosthetic valves make up the group at highest risk for development of recurrent IE.
Despite major advances in both medical and surgical interventions, IE remains a serious illness that can be associated with considerable morbidity and mortality. More data from prospective, randomized clinical trials are needed to determine the optimal approach to IE caused by multidrug-resistant bacteria. When these data become available, the Web- based version of these guidelines will be updated to assist clinicians in providing the most appropriate care of patients with IE.
The authors thank Drs Jose Miro, Peter B. Lockhart, and Anne H. Rowley for their thoughtful and valuable input during the preparation of this article. They also thank Lori Hinrichs for her generous secretarial support and Sarah Johnson for her expert copyediting. ⇓⇓
↵*Dr Levison is liaison from the Infectious Diseases Society of America.
↵†Dr Baltimore is liaison from the American Academy of Pediatrics.
↵‡Dr Falace is liaison from the American Dental Association.
The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest.
The full-text version of this statement (Circulation. 2005;111:e394–e433) is available on the Circulation Web site (http://circ.ahajournals.org/cgi/content/full/111/23/e394).
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