European Heart Journal (2009) 30, 2369–2413 doi:10.

1093/eurheartj/ehp285

ESC GUIDELINES

Guidelines on the prevention, diagnosis, and treatment of infective endocarditis (new version 2009)
The Task Force on the Prevention, Diagnosis, and Treatment of Infective Endocarditis of the European Society of Cardiology (ESC)
Endorsed by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and by the International Society of Chemotherapy (ISC) for Infection and Cancer
Authors/Task Force Members: Gilbert Habib (Chairperson) (France)*, Bruno Hoen (France), Pilar Tornos (Spain), Franck Thuny (France), Bernard Prendergast (UK), Isidre Vilacosta (Spain), Philippe Moreillon (Switzerland), Manuel de Jesus Antunes (Portugal), Ulf Thilen (Sweden), John Lekakis (Greece), Maria Lengyel (Hungary), ¨ Ludwig Muller (Austria), Christoph K. Naber (Germany), Petros Nihoyannopoulos (UK), Anton Moritz (Germany), Jose Luis Zamorano (Spain) ESC Committee for Practice Guidelines (CPG): Alec Vahanian (Chairperson) (France), Angelo Auricchio (Switzerland), Jeroen Bax (The Netherlands), Claudio Ceconi (Italy), Veronica Dean (France), Gerasimos Filippatos (Greece), Christian Funck-Brentano (France), Richard Hobbs (UK), Peter Kearney (Ireland), Theresa McDonagh (UK), Keith McGregor (France), Bogdan A. Popescu (Romania), Zeljko Reiner (Croatia), Udo Sechtem (Germany), Per Anton Sirnes (Norway), Michal Tendera (Poland), Panos Vardas (Greece), Petr Widimsky (Czech Republic) Document Reviewers: Alec Vahanian (CPG Review Coordinator) (France), Rio Aguilar (Spain), Maria Grazia Bongiorni (Italy), Michael Borger (Germany), Eric Butchart (UK), Nicolas Danchin (France), Francois Delahaye (France), Raimund Erbel (Germany), Damian Franzen (Germany), Kate Gould (UK), Roger Hall ´ ´ (UK), Christian Hassager (Denmark), Keld Kjeldsen (Denmark), Richard McManus (UK), Jose M. Miro (Spain), ´ ´ Ales Mokracek (Czech Republic), Raphael Rosenhek (Austria), Jose A. San Roman Calvar (Spain), Petar Seferovic (Serbia), Christine Selton-Suty (France), Miguel Sousa Uva (Portugal), Rita Trinchero (Italy), Guy van Camp (Belgium)
The disclosure forms of the authors and reviewers are available on the ESC website www.escardio.org/guidelines
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* Corresponding author. Gilbert Habib, Service de Cardiologie, CHU La Timone, Bd Jean Moulin, 13005 Marseille, France. Tel: þ33 4 91 38 63 79, Email: gilbert.habib@free.fr
The content of these European Society of Cardiology (ESC) Guidelines has been published for personal and educational use only. No commercial use is authorized. No part of the ESC Guidelines may be translated or reproduced in any form without written permission from the ESC. Permission can be obtained upon submission of a written request to Oxford University Press, the publisher of the European Heart Journal and the party authorized to handle such permissions on behalf of the ESC. Disclaimer. The ESC Guidelines represent the views of the ESC and were arrived at after careful consideration of the available evidence at the time they were written. Health professionals are encouraged to take them fully into account when exercising their clinical judgement. The guidelines do not, however, override the individual responsibility of health professionals to make appropriate decisions in the circumstances of the individual patients, in consultation with that patient, and where appropriate and necessary the patient’s guardian or carer. It is also the health professional’s responsibility to verify the rules and regulations applicable to drugs and devices at the time of prescription.

& The European Society of Cardiology 2009. All rights reserved. For permissions please email: journals.permissions@oxfordjournals.org.

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ESC Guidelines

Table of Contents
A. Preamble . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . B. Justification/scope of the problem . . . . . . . . . . . . . . . . . C. Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A changing epidemiology . . . . . . . . . . . . . . . . . . . . . Incidence of infective endocarditis . . . . . . . . . . . . . . . Types of infective endocarditis . . . . . . . . . . . . . . . . . . Microbiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . D. Pathophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . The valve endothelium . . . . . . . . . . . . . . . . . . . . . . . Transient bacteraemia . . . . . . . . . . . . . . . . . . . . . . . Microbial pathogens and host defences . . . . . . . . . . . . E. Preventive measures . . . . . . . . . . . . . . . . . . . . . . . . . . Evidence justifying the use of antibiotic prophylaxis for infective endocarditis in previous ESC recommendations Reasons justifying revision of previous ESC Guidelines . . Principles of the new ESC Guidelines . . . . . . . . . . . . . Limitations and consequences of the new ESC Guidelines F. Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Clinical features . . . . . . . . . . . . . . . . . . . . . . . . . . . Echocardiography . . . . . . . . . . . . . . . . . . . . . . . . . . Microbiological diagnosis . . . . . . . . . . . . . . . . . . . . . . Diagnostic criteria and their limitations . . . . . . . . . . . . G. Prognostic assessment at admission . . . . . . . . . . . . . . . . H. Antimicrobial therapy: principles and methods . . . . . . . . . General principles . . . . . . . . . . . . . . . . . . . . . . . . . . Penicillin-susceptible oral streptococci and group D streptococci . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Penicillin-resistant oral streptococci and group D streptococci . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Streptococcus pneumoniae, b-haemolytic streptococci (groups A, B, C, and G) . . . . . . . . . . . . . . . . . . . . . . Nutritionally variant streptococci . . . . . . . . . . . . . . . . Staphylococcus aureus and coagulase-negative staphylococci . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Methicillin-resistant and vancomycin-resistant staphylococci . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Enterococcus spp. . . . . . . . . . . . . . . . . . . . . . . . . . . . Gram-negative bacteria . . . . . . . . . . . . . . . . . . . . . . . Blood culture-negative infective endocarditis . . . . . . . . Fungi . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Empirical therapy . . . . . . . . . . . . . . . . . . . . . . . . . . Outpatient parenteral antibiotic therapy for infective endocarditis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . I. Complications and indications for surgery in left-sided native valve infective endocarditis . . . . . . . . . . . . . . . . . . . . . . . . Part 1. Indications and optimal timing of surgery . . . . . . . . . Heart failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Uncontrolled infection . . . . . . . . . . . . . . . . . . . . . . . Prevention of systemic embolism . . . . . . . . . . . . . . . . Part 2. Principles, methods, and immediate results of surgery . Pre- and peri-operative management . . . . . . . . . . . . . . Surgical approach and techniques . . . . . . . . . . . . . . . . Operative mortality, morbidity, and post-operative complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2371 2372 2372 2372 2373 2373 2373 2374 2374 2374 2374 2375 2375 2375 2376 2378 2378 2378 2379 2380 2382 2383 2383 2383 2384 2384 2384 2384 2386 2387 2387 2387 2387 2388 2388 2389 2391 2391 2391 2392 2393 2394 2394 2394 2394

J. Other complications of infective endocarditis Part 1. Neurological complications, antithrombotic therapy . . Part 2. Other complications (infectious aneurysms, acute renal failure, rheumatic complications, splenic abscess, myocarditis, pericarditis) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . K. Outcome after discharge and long-term prognosis . . . . . . Recurrences: relapses and reinfections . . . . . . . . . . . . Heart failure and need for valvular surgery . . . . . . . . . Long-term mortality . . . . . . . . . . . . . . . . . . . . . . . . Follow-up . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . L. Specific situations Part 1. Prosthetic valve endocarditis . . . . . . . . . . . . . . . . . . Part 2. Infective endocarditis on pacemakers and implantable defibrillators . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Part 3. Right-sided infective endocarditis . . . . . . . . . . . . . . . Part 4. Infective endocarditis in congenital heart disease . . . . Part 5. Infective endocarditis in the elderly . . . . . . . . . . . . . Part 6. Infective endocarditis during pregnancy . . . . . . . . . . . M. References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Abbreviations and acronyms
BCNIE CD CDRIE CHD CNS CT ELISA HF IA ICD ICE IE IVDA LDI MBC MIC MRI MRSA MSSA NBTE NVE OPAT PBP PCR PET PMP PPM PVE TEE TTE VISA blood culture-negative infective endocarditis cardiac device cardiac device-related infective endocarditis congenital heart disease coagulase-negative staphylococci computed tomography enzyme-linked immunosorbent assay heart failure infectious aneurysm implantable cardioverter defibrillator International Collaboration on Endocarditis infective endocarditis intravenous drug abuser local device infection minimal bactericidal concentration minimal inhibitory concentration magnetic resonance imaging methicillin-resistant Staphylococcus aureus methicillin-susceptible Staphylococcus aureus non-bacterial thrombotic endocarditis native valve endocarditis outpatient parenteral antibiotic therapy plasma-binding protein polymerase chain reaction positron emission tomography platelet microbicidal protein permanent pacemaker prosthetic valve endocarditis transoesophagal echocardiography transthoracic echocardiography vancomycin-intermediate Staphylococcus aureus

ESC Guidelines

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arise during the writing period must be notified to the ESC. The Task Force report received its entire financial support from the ESC and was developed without any involvement of the pharmaceutical, device, or surgical industry. The ESC Committee for Practice Guidelines (CPG) supervises and coordinates the preparation of new Guidelines and Expert Consensus Documents produced by Task Forces, expert groups, or consensus panels. The Committee is also responsible for the endorsement process of these Guidelines and Expert Consensus Documents or statements. Once the document has been finalized and approved by all the experts involved in the Task Force, it is submitted to outside specialists for review. The document is revised, and finally approved by the CPG and subsequently published. After publication, dissemination of the message is of paramount importance. Pocket-sized versions and personal digital assistant (PDA)-downloadable versions are useful at the point of care. Some surveys have shown that the intended users are sometimes unaware of the existence of guidelines, or simply do not translate them into practice. Thus, implementation programmes for new guidelines form an important component of knowledge dissemination. Meetings are organized by the ESC, and directed towards its member National Societies and key opinion leaders in Europe. Implementation meetings can also be undertaken at national levels, once the guidelines have been endorsed by the ESC member societies, and translated into the national language. Implementation programmes are needed because it has been shown that the outcome of disease may be favourably influenced by the thorough application of clinical recommendations. Thus, the task of writing Guidelines or Expert Consensus documents covers not only the integration of the most recent research, but also the creation of educational tools and implementation programmes for the recommendations. The loop between clinical research, writing of guidelines, and implementing them into clinical

A. Preamble
Guidelines and Expert Consensus Documents summarize and evaluate all currently available evidence on a particular issue with the aim of assisting physicians in selecting the best management strategy for an individual patient suffering from a given condition, taking into account the impact on outcome, as well as the risk/ benefit ratio of particular diagnostic or therapeutic means. Guidelines are no substitutes for textbooks. The legal implications of medical guidelines have been discussed previously. A great number of Guidelines and Expert Consensus Documents have been issued in recent years by the European Society of Cardiology (ESC) as well as by other societies and organizations. Because of the impact on clinical practice, quality criteria for development of guidelines have been established in order to make all decisions transparent to the user. The recommendations for formulating and issuing ESC Guidelines and Expert Consensus Documents can be found on the ESC website (http://www.escardio.org/ knowledge/guidelines/rules). In brief, experts in the field are selected and undertake a comprehensive review of the published evidence for management and/ or prevention of a given condition. A critical evaluation of diagnostic and therapeutic procedures is performed including assessment of the risk/ benefit ratio. Estimates of expected health outcomes for larger societies are included, where data exist. The level of evidence and the strength of recommendation of particular treatment options are weighed and graded according to predefined scales, as outlined in Tables 1 and 2. The experts of the writing panels have provided disclosure statements of all relationships they may have which might be perceived as real or potential sources of conflicts of interest. These disclosure forms are kept on file at the European Heart House, headquarters of the ESC. Any changes in conflict of interest that

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Table 1

Classes of recommendations

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Table 2

Levels of evidence

practice can then only be completed if surveys and registries are performed to verify that real-life daily practice is in keeping with what is recommended in the guidelines. Such surveys and registries also make it possible to evaluate the impact of implementation of the guidelines on patient outcomes. Guidelines and recommendations should help the physicians to make decisions in their daily practice, However, the ultimate judgement regarding the care of an individual patient must be made by the physician in charge of his/her care.

in clinical decision making. These recommendations were obtained by expert consensus after thorough review of the available literature. An evidence-based scoring system was used, based on a classification of the strength of recommendation and the levels of evidence.
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C. Epidemiology
A changing epidemiology
The epidemiological profile of IE has changed substantially over the last few years, especially in industrialized nations.1 Once a disease affecting young adults with previously well-identified (mostly rheumatic) valve disease, IE is now affecting older patients who more often develop IE as the result of health care-associated procedures, either in patients with no previously known valve disease14 or in patients with prosthetic valves.15 A recent systematic review of 15 population-based investigations accounting for 2371 IE cases from seven developed countries (Denmark, France, Italy, The Netherlands, Sweden, the UK, and the USA) showed an increasing incidence of IE associated with a prosthetic valve, an increase in cases with underlying mitral valve prolapse, and a decrease in those with underlying rheumatic heart disease.16 Newer predisposing factors have emerged—valve prostheses, degenerative valve sclerosis, intravenous drug abuse—associated with increased use of invasive procedures at risk for bacteraemia, resulting in health care-associated IE.17 In a pooled analysis of 3784 episodes of IE, it was shown that oral streptococci had fallen into second place to staphylococci as the leading cause of IE.1 However, this apparent temporal shift from predominantly streptococcal to predominantly staphylococcal IE may be partly due to recruitment/referral bias in specialized centres, since this trend is not evident in population-based epidemiological surveys of IE.18 In developing countries, classical patterns persist. In Tunisia, for instance, most cases of IE develop in patients with rheumatic valve disease, streptococci predominate, and up to 50% may be associated with negative blood cultures.19 In other African countries, the persistence of a high burden of rheumatic fever, rheumatic valvular heart diseases, and IE has also been highlighted.20 In addition, significant geographical variations have been shown. The highest increase in the rate of staphylococcal IE has been reported in the USA,21 where chronic haemodialysis, diabetes mellitus, and intravascular devices are the three main factors

B. Justification/scope of the problem
Infective endocarditis (IE) is a peculiar disease for at least three reasons: First, neither the incidence nor the mortality of the disease have decreased in the past 30 years.1 Despite major advances in both diagnostic and therapeutic procedures, this disease still carries a poor prognosis and a high mortality. Secondly, IE is not a uniform disease, but presents in a variety of different forms, varying according to the initial clinical manifestation, the underlying cardiac disease (if any), the microorganism involved, the presence or absence of complications, and underlying patient characteristics. For this reason, IE requires a collaborative approach, involving primary care physicians, cardiologists, surgeons, microbiologists, infectious disease specialists, and frequently others, including neurologists, neurosurgeons, radiologists, and pathologists.2 Thirdly, guidelines are often based on expert opinion because of the low incidence of the disease, the absence of randomized trials, and the limited number of meta-analyses.3,4 Several reasons justify the decision of the ESC to update the previous guidelines published in 2004.3 IE is clearly an evolving disease, with changes in its microbiological profile, a higher incidence of health care-associated cases, elderly patients, and patients with intracardiac devices or prostheses. Conversely, cases related to rheumatic disease have become less frequent in industrialized nations. In addition, several new national and international guidelines or state-of-the-art papers have been published in recent years.3 – 13 Unfortunately, their conclusions are not uniform, particularly in the field of prophylaxis, where conflicting recommendations have been formulated.3,4,6,8 – 13 Clearly, an objective for the next few years will be an attempt to harmonize these recommendations. The main objective of the current Task Force was to provide clear and simple recommendations, assisting health care providers

intermedius. female patients may have a worse prognosis and undergo valve surgery less frequently than their male counterparts. health care-associated IE (nosocomial and non-nosocomial).5 episodes/100 000 person-years in patients between 70 and 80 years of age. With regard to acquisition. and enterococci.oxfordjournals. the main predisposing factor for S. Causative microorganisms are most often staphylococci. 2010 Types of infective endocarditis IE should be regarded as a set of clinical situations which are sometimes very different from each other. Infective endocarditis with positive blood cultures This is the most important category.28 a. In all epidemiological studies of IE. although this higher proportion of men is poorly understood. and S. S.14. salivarius. according to the site of infection and the presence or absence of intracardiac foreign material: left-sided native valve IE. S. the following situations can be identified: community-acquired IE. In an attempt to avoid overlap. mutans. Furthermore.23 Incidence of infective endocarditis The incidence of IE ranges from one country to another within 3–10 episodes/100 000 person-years. S. streptococci. the following four categories of IE must be separated.27 Microbiology According to microbiological findings.22 In other countries.21. and IE in intravenous drug abusers (IVDAs). constellatus) must be distinguished since they Downloaded from eurheartj. milleri’ or ‘S. aureus IE may be intravenous drug abuse. Of note. in these surveys.ESC Guidelines 2373 prosthetic valve IE. and device-related IE (the latter including IE developing on pacemaker or defibrillator wires with or without associated valve involvement) (Table 3). the incidence of IE was very low in young patients but increased dramatically with age—the peak incidence was 14. and Gemella morbillorum. anginosus’ group (S. anginosus. Members of the ‘S. which includes species such as S. mitis.org by guest on August 31. Infective endocarditis due to streptococci and enterococci Oral (formerly viridans) streptococci form a mixed group of microorganisms. sanguis. right-sided IE. Microorganisms of this group are almost always susceptible to penicillin G. the male:female ratio is !2:1. associated with the development of Staphylococcus aureus endocarditis. the following categories are proposed: 1.24 – 26 This may reflect methodological differences between surveys rather than true variation. representing 85% of all IE. S. left-sided Table 3 Classification and definitions of infective endocarditis .

these account for up to 5% of all IE. durans. and the deposition of fibrin and platelets as a normal healing process. aphrophilus. Once adherent. Likewise. favouring infection by most types of organism. .g.29 – 31 especially S. inflammation. faecium. Actinobacillus actinomycetemcomitans. are the three species that cause IE. which are associated with inflammation. and microthrombi.org by guest on August 31. trigger local procoagulant activity. bacteraemia does not occur only after invasive procedures. H. Endothelial inflammation without valve lesions may also promote IE. H. staphylococcal prosthetic valve IE is more frequently due to coagulase-negative staphylococci (CNS) with oxacillin resistance. the agent of Whipple’s disease. and were until recently gathered under the name of Streptococcus bovis. Brucella. Gram- 4. fastidious Gram-negative bacilli of the HACEK group (Haemophilus parainfluenzae. aureus trigger their active internalization into valve endothelial cells. Diagnosis in such cases relies on serological testing.32 Overall. aureus and some other IE pathogens carry fibronectin-binding proteins on their surface. Eikenella corrodens. aureus and other potential intracellular pathogens.10 min]. aureus was the most frequent cause not only of IE but also of prosthetic valve IE. Tropheryma whipplei. They are usually sensitive to penicillin G. but its high incidence may explain why most cases of IE are unrelated to invasive procedures. which is most often susceptible to oxacillin. and. Such spontaneous bacteraemia is of low grade and short duration [1– 100 colony-forming units (cfu)/ml of blood for . Such nonbacterial thrombotic endocarditis (NBTE) facilitates bacterial adherence and infection.) share the ability to adhere to damaged valves. Streptococcus spp. Integrins are transmembrane proteins that can connect extracellular determinants to the cellular cytoskeleton. mechanical disruption of the endothelium results in exposure of underlying extracellular matrix proteins. Blood cultures may remain negative for many days after antibiotic discontinuation. and Enterococcus spp. as recently demonstrated. microulcers. where they can either persist and escape host defences and antibiotics. CNS can also cause native valve IE. or multiply and spread to distant organs. cell culture or gene amplification. In contrast. S. denitrificans). Bartonella. Group D streptococci form the ‘Streptococcus bovis/Streptococcus equinus’ complex. which frequently has an aggressive clinical course. Transient bacteraemia The role of bacteraemia has been studied in animals with catheterinduced NBTE.33 and in a similar proportion of elderly patients with IE. Cardiobacterium hominis. paraphrophilus. aureus. 2010 2. Kingella kingae.35 Of note. recently reclassified into other species (Abiotrophia and Granulicatella). Chlamydia. Infective endocarditis with negative blood cultures because of prior antibiotic treatment This situation arises in patients who received antibiotics for unexplained fever before any blood cultures were performed and in whom the diagnosis of IE was not considered. platelet proteins) and trigger platelet activation. Microbial pathogens and host defences Classical IE pathogens (S. often requiring a longer duration of antibiotic treatment. and nurture infected vegetations in which they can survive. the production of tissue factor. E. including commensal species of the human intestinal tract. E. but also as a consequence of chewing and tooth brushing. usually the diagnosis is eventually considered in the face of relapsing febrile episodes following antibiotic discontinuation.36 3. However.34 Thus. lugdunensis. and fungi. Infective endocarditis frequently associated with negative blood cultures They are usually due to fastidious organisms such as nutritionally variant streptococci.22 Conversely. S. Hence. Infective endocarditis associated with constantly negative blood cultures They are caused by intracellular bacteria such as Coxiella burnetii. faecalis. Among enterococci. Degenerative valve lesions are detected by echocardiography in up to 50% of asymptomatic patients over 60 years. fibrinogen. fibronectin. and to a lesser extent E.2374 tend to form abscesses and cause haematogenously disseminated infection. should also be distinguished since they are often tolerant to penicillin [minimal bactericidal concentration (MBC) much higher than the mimimal inhibitory concentration (MIC)]. as in rheumatic carditis. influenzae. like oral streptococci. and one occurring on physically undamaged endothelium. ESC Guidelines D. when activated endothelial cells bind fibronectin they provide an adhesive surface to circulating staphylococci. Staphylococcal infective endocarditis Traditionally. aureus. H. Integrins of the b1 family bind circulating fibronectin to the endothelial surface while S.26. Both the magnitude of bacteraemia and the ability of the pathogen to attach to damaged valves are important. Endothelial damage may result from mechanical lesions provoked by turbulent blood flow. and causative organisms are most often oral streptococci or CNS. Downloaded from eurheartj.. b. Pathophysiology The valve endothelium The normal valve endothelium is resistant to colonization and infection by circulating bacteria. This might account for the increased risk of IE in the elderly. there are at least two scenarios for primary valve infection: one involving a physically damaged endothelium. Local inflammation triggers endothelial cells to express integrins of the b1 family (very late antigen). native valve staphylococcal IE is due to S. adherent bacteria must escape host defences. at least in community-acquired IE. Following colonization. electrodes or catheters.37 They are equipped with numerous surface determinants that mediate adherence to host matrix molecules present on damaged valves (e. promoting IE due to S. However. and K. or degenerative changes in elderly individuals. in a recent study of 1779 cases of IE collected prospectively in 16 countries. nutritionally variant ‘defective’ streptococci.oxfordjournals.

45. whereas similar bacteria recovered from patients with other types of infection are susceptible. but to limit prophylaxis to the highest risk patients. flossing. (3) The indications for antibiotic prophylaxis for IE should be reduced in comparison with previous recommendations. they may be the target of platelet microbicidal proteins (PMPs). and contradictory observational studies. particularly in patients with predisposing factors.47 and (ii) the bacteraemia that causes IE in the majority of patients appears to derive from another source. Even strict adherence to generally accepted recommendations for prophylaxis might have little impact on the total number of patients with IE in the community.42. bacteraemia can be observed independently of dental procedures. The incidence after other types of medical procedures is even less well established. Preventive measures Evidence justifying the use of antibiotic prophylaxis for infective endocarditis in previous ESC recommendations The principle of prophylaxis for IE was developed on the basis of observational studies in the early 20th century. non-evidence-based use of antibiotics for all at-risk patients undergoing interventional procedures. data from animal experiments. studies on isolated aspects of the hypothesis.9 – 11 Although the individual recommendations of these committees differ in some aspects. Incidence of bacteraemia after dental procedures and during daily routine activities The reported incidence of transient bacteraemia after dental procedures is highly variable and ranges from 10 to 100%.org by guest on August 31. Lack of scientific evidence for the efficacy of infective endocarditis prophylaxis Studies reporting on the efficacy of antibiotic prophylaxis to prevent or alter bacteraemia in humans after dental procedures are contradictory.40 Downloaded from eurheartj. However. which are produced by activated platelets and kill microbes by disturbing their plasma membrane. no potential index procedure preceding the first clinical appearance of IE can be identified.26 Even if effectiveness and compliance are assumed to approximate 100%. transient bacteraemia is reported to occur frequently in the context of daily routine activities such as tooth brushing. The main reasons justifying the revision of previous recommendations are the following: 1. this observation leads to two conclusions: (i) IE prophylaxis can at best only protect a small proportion of patients. escaping PMP-induced killing is a typical characteristic of IE-causing pathogens. (c) Antibiotic administration carries a small risk of anaphylaxis. Bacteria recovered from patients with IE are consistently resistant to PMP-induced killing. the Task Force aimed to avoid extensive.6.41 This may be a result of different analytical methods and sampling procedures. Risks and benefits of prophylaxis The following considerations are critical with respect to the assumption that antibiotic prophylaxis can efficiently prevent IE in patients who are at increased lifetime risk of the disease: 3. the concept of antibiotic prophylaxis efficacy itself has never been investigated in a prospective randomized controlled trial. and rates of post-procedural bacteraemia are higher in this group.39 The basic hypothesis is based on the assumption that bacteraemia subsequent to medical procedures can cause IE. However. A better parameter. In contrast. and these results should be interpreted with caution. and that prophylactic antibiotics can prevent IE in these patients by minimizing or preventing bacteraemia. The recommendations for prophylaxis are based in part on the results of animal studies showing that antibiotics could prevent the development of experimental IE after inoculation of bacteria.52 to support the necessity of IE prophylaxis. or by altering bacterial properties leading to reduced bacterial adherence on the endothelial surface.50 and so far there are no data demonstrating that reduced duration or frequency of bacteraemia after any medical procedure leads to a reduced procedure-related risk of IE.ESC Guidelines 2375 (a) Increased lifetime risk of IE is not an ideal measure of the extent to which a patient may benefit from antibiotic prophylaxis for distinct procedures.44 positive bacteria are resistant to complement. case reports.46 These estimations demonstrate the huge number of patients that will require treatment to prevent one single case of IE. Recent guideline committees of national cardiovascular societies have re-evaluated the existing scientific evidence in this field. Similarly. or chewing. the extent to which antiobiotic use for IE prophylaxis could be implicated in the general problem of resistance is unknown. ranges from 1:14 000 000 for dental procedures in the average population to 1:95 000 in patients with previous IE. in patients with poor dental health.43 It therefore appears plausible that a large proportion of IE-causing bacteraemia may derive from these daily routine activities.51.44 2.48 (d) Widespread and often inappropriate use of antibiotics may result in the emergence of resistant microorganisms.49. In addition. 2010 Reasons justifying revision of previous ESC Guidelines Within these guidelines.52 Finally. However.53 and assumptions on efficacy are based on non-uniform expert opinion. the procedure-related risk. (2) Prophylaxis should be limited to the highest risk patients (patients with the highest incidence of IE and/or highest risk of adverse outcome from IE). These findings emphasize the importance of good oral hygiene and regular dental review to prevent IE. no sufficient evidence exists from case –control studies36. no case of fatal anaphylaxis has been reported in the literature after oral amoxicillin administration for prophylaxis of IE. E.oxfordjournals.38 Thus. they did uniformly and independently draw four conclusions: (1) The existing evidence does not support the extensive use of antibiotic prophylaxis recommended in previous guidelines. . (b) In the majority of patients.

please refer to text. *For management when infections are present.54. Table 5 Recommendations for prophylaxis of infective endocarditis in highest risk patients according to the type of procedure at risk Class of recommendation. 2010 a b Class of recommendation.oxfordjournals. Patients with the highest risk of infective endocarditis (Table 4) They include three categories of patients: (a) Patients with a prosthetic valve or a prosthetic material used for cardiac valve repair: these patients have a higher risk of IE. a higher mortality from IE and more often develop complications of the disease than patients with native valves and an identical pathogen. Level of evidence.2376 (4) Good oral hygiene and regular dental review are of particular importance for the prevention of IE. – ESC Guidelines to limit its indication to patients with the highest risk of IE (Table 4) undergoing the highest risk procedures (Table 5). Level of evidence. b a .12 the Task Force decided: – to maintain the principle of antibiotic prophylaxis when performing procedures at risk of IE in patients with predisposing cardiac conditions. but 1. Principles of the new ESC Guidelines Although recent guidelines proposed limitation of prophylaxis to patients at increased risk of adverse outcome of IE6 or even complete cessation of antibiotic prophylaxis in any patient groups.org by guest on August 31.55 Table 4 Cardiac conditions at highest risk of infective endocarditis for which prophylaxis is recommended when a high risk procedure is performed Downloaded from eurheartj.

vancomycin or another suitable agent should be administered.v. If undertaken. cefazolin or ceftriaxone 1 g i. Highest risk procedures (Table 5) a. or other prostheses. ampicillin. ii.62. for children.v. consultation with an infectious diseases specialist is recommended. Fluoroquinolones and glycopeptides are not recommended due to their unclear efficacy and the potential induction of resistance. The impact of increasing resistance of these pathogens for the efficacy of antibiotic prophylaxis is unclear. for adults or 50 mg/kg i. angio-oedema. Vancomycin should only be administered to patients unable to tolerate b-lactams.59 After surgical repair with no residual defects. aureus (MRSA). Currently no data are available on (a) the incidence of IE after such procedures and (b) the efficacy of antibiotics for prevention. b. iii.58. Dermatological or musculoskeletal procedures. Education of patients at risk of IE is paramount. Vancomycin or another suitable agent should be administered if the infection is known or suspected to be caused by a methicillin-resistant strain of S. mitral valve prolapse.g.57 (c) Patients with congenital heart disease (CHD). Body piercing and tattooing. or urticaria after intake of penicillin and ampicillin. Dental procedures Procedures at risk involve the manipulation of the gingival or periapical region of teeth or perforation of the oral mucosa (including scaling and root canal procedures).oxfordjournals. it is reasonable that the therapeutic regimen contains an agent active against staphylococci and b-haemolytic streptococci. conduits. and is not recommended in other situations. bicuspid aortic valve. prophylaxis is not recommended in patients undergoing these procedures. higher mortality and incidence of complications than patients with a first episode of IE. or musculoskeletal tissue. amoxicillin.g. or 50 mg/kg i. Respiratory tract procedures. Although AHA guidelines recommend prophylaxis in cardiac transplant recipients who develop cardiac valvulopathy. Other at-risk procedures There is no compelling evidence that bacteraemia resulting from either respiratory tract procedures. in particular those with complex cyanotic heart disease and those who have post-operative palliative shunts. The main targets for antibiotic prophylaxis in these patients are oral streptococci. procedures should be performed under strictly sterile conditions though antibiotic prophylaxis is not recommended. * Alternatively cephalexin 2 g i. Gastrointestinal or genitourinary procedures. Patients listed in Table 4 who undergo an invasive respiratory tract procedure to treat an established infection. Table 6 summarizes the main regimens of antibiotic prophylaxis recommended before dental procedures. Vancomycin should be given to patients unable to tolerate a b-lactam. gastrointestinal or genitorurinary procedures. . Prophylaxis is not recommended for any other form of native valve disease (including the most commonly identified conditions.60 The ESC Task Force does not recommend prophylaxis in such situations. If infection is caused by a known or suspected strain of resistant enterococcus.org by guest on August 31. should receive an antibiotic regimen which contains an anti-staphylococcal penicillin or cephalosporin. and piercing and tattooing procedures should be discouraged. i. e. dermatological or musculoskeletal procedures Downloaded from eurheartj. In the case of an established infection or if antibiotic therapy is indicated to prevent wound infection or sepsis associated with a gastrointestinal or genitourinary tract procedure in patients described in Table 4.v. If the infection is known or suspected to be caused by MRSA. particularly for those individuals with CHD who are at increased susceptibility for the acquisition of IE.ESC Guidelines 2377 cause IE. e.g.v.56. e. iv. or vancomycin. the probability of IE from dental origin is extremely low in these patients. (b) Patients with previous IE: they also have a greater risk of new IE.61 particularly when piercing involves the tongue. Prophylaxis should only be considered for patients described in Table 4 undergoing any of these procedures. an anti-staphylococcal penicillin or cephalosporin.63 although publication bias may overestimate the problem since millions of people are tattooed and pierced around the world and CHD concerns only 1% of the general population. Case reports of IE after piercing and tattooing are increasing. and calcific aortic stenosis). for children. In addition. 2010 Table 6 Recommended prophylaxis for dental procedures at risk Cephalosporins should not be used in patients with anaphylaxis.6 this is not supported by strong evidence. although the risk of adverse outcome is high when IE occurs in transplant patients. the Task Force recommends prophylaxis for the first 6 months after the procedure until endothelialization of the prosthetic material occurs. Vancomycin or clindamycin may be used in patients unable to tolerate a b-lactam. it is reasonable that the antibiotic regimen includes an agent active against enterococci. Thus. drainage of an abscess. For patients described in Table 4 undergoing surgical procedures involving infected skin (including oral abscesses). These growing social trends are a cause for concern. skin structure. 2.

66 Finally. the Task Force strongly recommends prospective evaluation in the wake of these new guidelines to evaluate whether reduced use of prophylaxis is associated with a change in the incidence of IE. Practitioners may also have a reasonable fear of litigation should prophylaxis be withdrawn. dentists. Aseptic measures are mandatory during venous catheters manipulation and during any invasive procedures in order to reduce the rate of health care-associated IE F. Cardiac or vascular surgery.org by guest on August 31. Ethically. unless the latter procedure is urgent. They represent up to 30% of all cases of IE and are characterized by an increasing incidence and a severe prognosis. The early involvement of a cardiologist and an infectious disease specialist to guide management is highly recommended. and weight loss. Diagnosis Clinical features The diverse nature and evolving epidemiological profile of IE ensure it remains a diagnostic challenge. It is strongly recommended that potential sources of dental sepsis are eliminated at least 2 weeks before implantation of a prosthetic valve or other intracardiac or intravascular foreign material. Good oral hygiene and regular dental review have a very important role in reducing the risk of IE.64 Although routine antimicrobial prophylaxis administered before most invasive procedures is not recommended. Heart Downloaded from eurheartj. after antibiotic pre-treatment. Patients may therefore present to a variety of specialists who may consider a range of alternative diagnoses including chronic infection. many may wish to continue with routine prophylaxis. poor appetite. or malignancy. in the immunocompromised patient and in IE involving less virulent or atypical organisms. rheumatological and autoimmune disease.2378 v. aseptic measures during the insertion and manipulation of venous catheters and during any invasive procedures are mandatory to reduce the rate of this infection. and terminated 48 h afterwards.oxfordjournals. the presence or absence of pre-existing cardiac disease. As Table 7 Clinical presentation of infective endocarditis *NB: Fever may be absent in the elderly.67 The clinical history of IE is highly variable according to the causative microorganism. these practitioners need to discuss the potential benefit and harm of antibiotic prophylaxis with their patients before a final decision is made. Up to 90% of patients present with fever. and their patients. Thus. peri-operative antibiotic prophylaxis should be considered due to the increased risk and adverse outcome of an infection. thus representing an important health problem. the Task Force proposes limitation of antibiotic prophylaxis to patients with the highest risk of IE undergoing the highest risk dental procedures. It may present as an acute.1 year after surgery) prosthetic valve infections are CNS and S. Procedures causing health care-associated IE. often associated with systemic symptoms of chills. and the mode of presentation. The most frequent microorganisms underlying early (. Following informed review and discussion. and these views should be respected. In patients undergoing implantation of a prosthetic valve or intravascular prosthetic or other foreign material. vi. but also as a subacute or chronic disease with low grade fever and non-specific symptoms which may thwart or confuse initial assessment. In summary. cardiologists. . ESC Guidelines neither the previous guidelines nor the current proposed modifications are based on strong evidence.65 though unnecessarily so since adherence to recognized guidelines affords robust legal protection. rapidly progressive infection. IE should be suspected in a variety of very different clinical situations (Table 7). the current recommendations are not based on appropriate evidence. aureus. but reflect an expert consensus of opinion. 2010 Limitations and consequences of the new ESC Guidelines The Task Force understands that these updated recommendations dramatically change long-established practice for physicians. repeated if the procedure is prolonged. Prophylaxis should be started immediately before the procedure.

68 In a febrile patient. The utility of both modes of investigation is diminished when applied indiscriminately.3 However. TEE ¼ transoesophageal echocardiography. management. b a murmurs are found in up to 85% of patients. and appropriate application in the context of simple clinical criteria improves diagnostic yield71 (Figure 1). however. and emboli to the brain. Classic textbook signs may still be seen in the developing world. . TEE ¼ transoesophageal echocardiography.70 Echocardiography must be performed rapidly.69 in whom fever is less frequent than in younger individuals. anaemia. as patients generally present at an early stage of the disease. and follow-up (Table 8) of IE is clearly recognized. lung or spleen occur in 30% of patients and are often the presenting feature. TTE ¼ transthoracic echocardiography. An exception is the patient with S. Echocardiography Transthoracic and transoesophageal echocardiography (TTE/TEE) are now ubiquitous and their fundamental importance in diagnosis. Roth spots. 2010 Class of recommendation. A high index of suspicion and low threshold for investigation to exclude IE are therefore essential in these and other high-risk groups. and glomerulonephritis remain common. Level of evidence. and microscopic haematuria.ESC Guidelines 2379 Table 8 Role of echocardiography in infective endocarditis Downloaded from eurheartj. these lack specificity and have not been integrated into current diagnostic criteria. leukocytosis. aureus Figure 1 Indications for echocardiography in suspected infective endocarditis. IE ¼ infective endocarditis.7 Atypical presentation is common in elderly or immunocompromised patients. although peripheral stigmata of IE are increasingly uncommon elsewhere. the diagnostic suspicion may be strengthened by laboratory signs of infection. *TEE is not mandatory in isolated right-sided native valve IE with good quality TTE examination and unequivocal echocardiographic findings. TTE ¼ transthoracic echocardiography. vascular and immunological phenomena such as splinter haemorrhages. as soon as IE is suspected.oxfordjournals.org by guest on August 31. However. such as elevated C-reactive protein or sedimentation rate.

As a result. which has two implications: (1) there is no rationale for delaying blood sampling to coincide with peaks of fever. magnetic resonance imaging (MRI). and radionuclide scanning] have yet to be evaluated in IE. prosthetic valves). follow-up echocardiography to monitor complications and response to treatment is mandatory (Table 8). not yet present (or already embolized).76 while the roles of three-dimensional echocardiography and other alternative modes of imaging [computed tomography (CT).77 Microbiological diagnosis 1.oxfordjournals.2 mm). each containing 10 mL of blood obtained from a peripheral vein using meticulous sterile technique. subculture onto chocolate agar plates may .79. The need for culture prior to antibiotic administration is self-evident. and in non-vegetant IE. diagnosis may be particularly challenging in IE affecting intracardiac devices. particularly at the earliest stage of disease.13. small abscesses may be difficult to identify. even with use of TEE. and in the presence of a prosthetic device (especially in the mitral position). Other advances in imaging technology have had minimal impact in routine clinical practice. and in association with small intracardiac tumours (typically fibroelastomata).org by guest on August 31. especially for potentially ‘contaminants’ such as CNS or corynebacteria. as compared with TEE. and its devastating effects once intracardiac infection is established. Additional echocardiographic study is seldom helpful. The use of harmonic imaging has improved study quality. abscess. particularly for the assessment of the perivalvular extent of abscesses and pseudoaneurysms.74 In cases with an initially negative examination. Appearances resembling vegetations may be seen in degenerative or myxomatous valve disease. primary antiphospholipid syndrome. although surveys of contemporary practice reveal frequent violations of this rule. systemic lupus (inflammatory Libman –Sacks lesions). a single positive blood culture shoud be regarded cautiously for establishing the diagnosis of IE. Although IE caused by anaerobes is uncommon.78 Sampling from central venous catheters should be avoided in view of the high risk of contaminants (false positives.72 Three echocardiographic findings are major criteria in the diagnosis of IE: vegetation. chordal rupture. advanced malignancy (marantic endocarditis). repeat TTE/TEE must be performed 7–10 days later if the clinical level of suspicion is still high. degenerative calcified lesions. aureus infection. in the post-operative period.2380 ESC Guidelines Table 9 Anatomic and echocardiographic definitions Downloaded from eurheartj. positron emission tomography (PET). Three sets (including at least one aerobic and one anaerobic). and new dehiscence of a prosthetic valve (see Table 9 for anatomical and echocardiographic definitions). if vegetations are very small (.73 However. bacteraemia is almost constant. Blood cultures Positive blood cultures remain the cornerstones of diagnosis and provide live bacteria for susceptibility testing. is virtually always sufficient to identify the usual microorganisms—the diagnostic yield of repeated sampling thereafter is low. Multislice CT has recently been shown to give good results in the evaluation of IE-associated valvular abnormalities. with little additional information derived after the second or third assessment. The sensitivity of TTE ranges from 40 to 63% and that of TEE from 90 to 100%. valvular thrombus. When cultures remain negative at 5 days. cultures should be incubated in both aerobic and anaerobic atmospheres to detect organisms such as Bacteroides or Clostridium species. 2010 bacteraemia where routine echocardiography is justified in view of the frequency of IE in this setting and of the virulence of this organism.80 In IE. and rheumatoid disease. or even earlier in case of S. Similarly.75 However. Identification of vegetations may be difficult in the presence of preexisting severe lesions (mitral valve prolapse. typically staphylococcal) and misleading findings. and (2) virtually all blood cultures (or a majority of them) are positive.

org by guest on August 31. 2.ESC Guidelines 2381 cultures in this situation. and immunocompromised states (Table 10). Early consultation with an infectious disease specialist is recommended.81 A proposed scheme for the identification of microorganisms in culture-positive and culture-negative IE is provided in Figure 2. . An increasingly common scenario is infection by fastidious organisms with limited proliferation under conventional culture conditions. 2010 Figure 2 Microbiological diagnosis in culture-positive and culture-negative infective endocarditis. Prolonged culture is associated with rising likelihood of contamination. underlying the need for withdrawing antibiotics and repeat blood Downloaded from eurheartj. *If the organism remains unidentified and the patient is stable. pacemakers. renal failure. or requiring specialized tools for identification (see Section C).5– 31% of all cases of IE. Table 10 Investigation of rare causes of culture-negative infective endocarditis PCR ¼ polymerase chain reaction. indwelling venous lines. IE ¼ infective endocarditis. PCR ¼ polymerase chain reaction. and alternative techniques (or an alternative diagnosis) should be considered at this stage. often delaying diagnosis and the initiation of treatment. with profound impact on clinical outcome. consider antibiotic withdrawal and repeat blood cultures. Histological/immunological techniques Pathological examination of resected valvular tissue or embolic fragments remains the gold standard for the diagnosis of IE and may also guide antimicrobial treatment if the causative agent can be identified allow identification of a fastidious organism. 3.82 BCNIE arises most commonly as a consequence of prior antibiotic administration.83 These organisms may be particularly common in IE affecting patients with prosthetic valves.oxfordjournals. Culture-negative infective endocarditis and atypical organisms Blood-culture negative IE (BCNIE) occurs in 2.

Bashore T. inability to provide information concerning bacterial sensitivity to antimicrobial agents. and widespread use of TEE. Diagnostic criteria and their limitations The Duke criteria.88 Improvements (including the availability of real-time PCR and a wider range of comparator gene sequences)89 and availability of other emerging technologies90 will address many of these deficiencies.85 The technique has been validated using valve tissue from patients undergoing surgery for IE.92 based upon clinical. Recent amendments recognize the role of Q-fever (a worldwide zoonosis caused by Coxiella burnetii).30:633 –638. Sexton DJ.93. false negatives due to the presence of PCR inhibitors in clinical samples. Clin Infect Dis 2000. but results still require careful specialist interpretation.91 the technique seems unlikely to supersede blood cultures as a prime diagnostic tool. Electron microscopy has high sensitivity and may help to characterize new microorganisms. Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. echocardiographic. 2010 Adapted from Li JS. but is time consuming and expensive.86 Although there are several advantages. Ryan T. Fowler VG. 4. Although PCR positivity has been proposed as a major diagnostic criterion for IE. Jr. Corey GR. and persistent positivity despite clinical remission. Indeed.87. Mick N. PCR of excised valve tissue or embolic material should be performed in patients with negative blood cultures who undergo valve surgery or embolectomy. and the resultant so-called modified Duke criteria are now recommended for diagnostic classification (Table 11). and recent data demonstrate similar utility for staphylococci. Incorporation of these methods into accepted diagnostic criteria awaits prospective validation. Molecular biology techniques The polymerase chain reaction (PCR) allows rapid and reliable detection of fastidious and non-culturable agents in patients with IE.2382 ESC Guidelines Table 11 Modified Duke criteria for the diagnosis of infective endocarditis (adapted from Li et al. positive PCR can persist for months after successful eradication of infection. risk of contamination. and microbiological findings provide high sensitivity and specificity (80% overall) for the diagnosis of IE. by means of special stains or immunohistological techniques. Nettles R.oxfordjournals.. The presence of a positive PCR at the time of pathological examination of the excised valve is not synonymous with treatment failure unless valve cultures are positive. and ELISA detection of Legionella species has been described using this technique.84 Immunological analysis of urine may allow detection of microorganism degradation products. including extreme sensitivity.94 . Coxiella burnetii and Bartonella species may be easily detected by serological testing using indirect immunofluorescence or enzyme-linked immunosorbent assay (ELISA).org by guest on August 31. 94) Downloaded from eurheartj. inherent limitations include the lack of reliable application to whole blood samples. increasing prevalence of staphylococcal infection.

68.96. The risk of patients with left-sided IE has been formally Downloaded from eurheartj. and echocardiographic findings (Table 12). the infecting organism. e. prognostic assessment at admission can be performed using simple clinical. especially in settings where sensitivity of the modified criteria is diminished.108.102 – 104 Nowadays.107 Predictably. depressed left ventricular function. both in animal experiments and in humans.96 When three of these factors are present.109 Table 12 Predictors of poor outcome in patients with IE . these patients should be followed up closely and referred to tertiary care centres with surgical facilities. Host defences are of little help. A high degree of co-morbidity. However. TTE must be performed first.g. In summary. It will also allow identification of patients with the worst immediate outcome who will benefit from closer follow-up and a more aggressive treatment strategy (eg. Prognostic assessment at admission The in-hospital mortality rate of patients with IE varies from 9.ESC Guidelines 2383 assessed according to these variables. The Duke criteria are useful for the classification of IE but do not replace clinical judgement. Quick identification of patients at highest risk of death may offer the opportunity to change the course of the disease and improve prognosis. Clear deficiencies remain and clinical judgement remains essential. aureus infection are at highest risk of death and need for surgery in the active phase of the disease. 2010 H. and the presence of stroke are also predictors of poor in-hospital outcome. Surgery contributes by removing infected material and draining abscesses. the risk reaches 79%. echocardiography and blood cultures are the cornerstone of diagnosis of IE. This explains why bactericidal regimens are more effective than bacteriostatic therapy. but both TTE and TEE should ultimately be performed in the majority of cases of suspected or definite IE.100. and should be used to choose the best therapeutic option.106 In those patients who need urgent surgery.105. persistent infection and renal failure are predictors of mortality.96 Therefore. microbiological. 50% of patients undergo surgery during hospitalization. it should be kept in mind that these modifications await formal validation and that the original criteria were initially developed to define cases of IE for epidemiological studies and clinical trials. when infection affects a prosthetic valve or pacemaker lead. and echocardiographic parameters.96 – 102 but differs considerably from patient to patient.97 Patients with heart failure (HF). Prognosis in IE is influenced by four main factors: patient characteristics. Antimicrobial therapy: principles and methods General principles Successful treatment of IE relies on microbe eradication by antimicrobial drugs.97 – 99.14. insulin-dependent diabetes. and/or S. patients with an indication for surgery who cannot proceed due to prohibitive surgical risk have the worst prognosis. the presence or absence of cardiac and non-cardiac complications. urgent surgery). and when IE affects the right heart95 (particularly in IVDAs).org by guest on August 31. G. when blood cultures are negative. periannular complications.15 In summary.oxfordjournals.14.6 to 26%.

Downloaded from eurheartj. except for the use of short-term 2-week therapy. In non-complicated cases. ceftriaxone or vancomycin for 6 weeks. antibiotic therapy for penicillin-resistant and penicillin-susceptible oral streptococci is qualitatively similar (Table 13). b-haemolytic streptococci (groups A. Slow-growing and dormant microbes display phenotypic tolerance towards most antimicrobials (except rifampin to some extent). Compiling four of them.120 – 123 Most penicillin MICs were !1 mg/L. 47/60 (78%) patients were treated with penicillin G or ceftriaxone mostly combined with aminoglycosides. shortterm 2-week therapy can be administered by combining penicillin or ceftriaxone with gentamicin or netilmicin. It is associated with meningitis in up to 30% of cases. IE due to group B streptococci was once associated with the peripartum period. penicillin must be avoided because it poorly penetrates the cerebrospinal fluid.99% of group D streptococci remain penicillin susceptible. which has not been formally investigated.2384 Aminoglycosides synergize with cell wall inhibitors (i. oralis.126 Group A streptococci are uniformly susceptible to b-lactams.2 mg/L). but now occurs in other adults. 2010 Streptococcus pneumoniae.125 –2 mg/L) and fully-resistant (MIC . intermedius)—is relatively rare. and justify the need for prolonged therapy (6 weeks) to sterilize infected heart valves fully. B.128 possibly due to delayed diagnosis and treatment.95%. Penicillin-susceptible oral streptococci and group D streptococci Recommended regimens against susceptible streptococci (penicillin MIC 0. some guidelines consider a MIC . In both NVE and PVE. oral streptococci) and eradicate problematic organisms (e. anginosus.129 Seven patients had large vegetations (. One major hindrance to drug-induced killing is bacterial antibiotic tolerance. especially the elderly.30% of relatively and fully . but escape drug-induced killing and may resume growth after treatment discontinuation. milleri group (S.125 IE due to group A. they are still susceptible to growth inhibition by the drug.10 mm) and underwent surgery. One recent study reported on eight cases of successful treatment with penicillin G or ceftriaxone plus gentamicin. Group B. Tolerant microbes are not resistant. Recent large strain collections report .5 mg/L as fully resistant. the duration of treatment is based on the first day of effective antibiotic therapy. However.109a the choice of antibiotic being based on the susceptibility of the latest recovered bacterial isolate.). except for staphylococcal PVE where the regimen should include rifampin whenever the strain is susceptible.e. Penicillin-resistant oral streptococci and group D streptococci Penicillin-resistant oral streptococci are classified as relatively resistant (MIC 0.e. The same holds true for penicillinresistant strains (MIC . Little experience exists with highly resistant isolates (MIC .113.116 However. C. Bactericidal drug combinations are preferred to monotherapy against tolerant organisms. but is otherwise similar.127 Antibiotic treatment is similar to that of oral streptococci (Table 13). not for PVE. and S. Fifty patients (83%) were cured and 10 (17%) died. the post-operative antibiotic regimen should be that recommended for NVE.3. which is associated with higher rates of complications and treatment failure (up to 40%). . Some bacteria carry mutations rendering them tolerant during both active growth and stationary (dormant) phases. in prosthetic valve endocarditis (PVE). but to patients’ underlying conditions. Nutritionally variant streptococci They produce IE with a protracted course.1 mg/L) is similar to that of oral streptococci (Table 13). a new full course of treatment should only start if valve cultures are positive. Teicoplanin has been proposed as an alternative3 and requires loading doses (6 mg/kg/12 h for 3 days) followed by 6–10 mg/kg/day.g. After surgery.122 Treatment outcome was similar in PVE and NVE. Antibiotic recommendations include penicillin G.125 mg/L) are summarized in Table 13.1 mg/L) without meningitis. In cases with meningitis. combined with an aminoglycoside for at least the first 2 weeks. pneumoniae has become rare since the introduction of antibiotics.4 mg/L)—vancomycin might be preferred in such circumstances. Ceftriaxone alone or combined with gentamicin or netilmicin given once a day is particularly convenient for outpatient therapy.0. except that short-term therapy is not recommended.121 Hence. S. Enterococcus spp.114 The latter two studies demonstrated that gentamicin and netilmicin can be given once daily in patients with IE due to susceptible streptococci and normal renal function. C. B.119 Conversely. and some with either clindamycin or aminoglycosides alone. and G streptococci and S. b-lactams and glycopeptides) for bactericidal activity and are useful to shorten the duration of therapy (e. not on the day of surgery. in penicillin-resistant cases aminoglycoside treatment may be prolonged to 3 –4 weeks and short-term therapy regimens are not recommended. milleri produce abscesses and thus may require adjunctive surgery.113 – 115 Patients allergic to b-lactams should receive vancomycin.org by guest on August 31. Treatment of penicillin-susceptible strains (MIC 0. e.124 which requires special consideration in cases with penicillin resistance.g.118. Loading is critical because the drug is highly bound to serum proteins (!98%) and penetrates slowly into vegetations. ESC Guidelines resistant S.7.126 Mortality of Group B PVE is very high and cardiac surgery is recommended. whereas other serogroups may display resistance. and G) IE due to S. mitis and S.110 – 112 Cure rate is expected to be . Death was not related to resistance. constellatus. They are present in vegetations and biofilms.oxfordjournals. Drug treatment of PVE should last longer (at least 6 weeks) than that of native valve endocarditis (NVE) (2–6 weeks).3. In NVE needing valve replacement by a prosthesis during antibiotic therapy. i. or G streptococci—including the S. only limited retrospective studies have assessed its efficacy in streptococcal117 and enterococcal118 IE. C. and should be replaced with ceftriaxone or cefotaxime alone or in combination with vancomycin. Treatment guidelines for penicillin-resistant streptococcal IE rely on retrospective series.110 Such resistant streptococci are increasing.g.7. However.

1 h after infusion is completed). b a . d Or ampicillin. e Preferred for outpatient therapy.112 i Serum vancomycin concentrations should achieve 10 –15 mg/L at pre-dose (trough) level and 30 –45 mg/L at post-dose level (peak. g Only if non complicated native valve IE. same dosages as amoxicillin. h Renal function and serum gentamicin concentrations should be monitored once a week. When given in a single daily dose. f Paediatric doses should not exceed adult doses. c 6-week therapy in PVE. 1 h after injection) serum concentrations should be 10 –12 mg/L. 2010 See text for other streptococcal species.ESC Guidelines 2385 Table 13 Antibiotic treatment of infective endocarditis due to oral streptococci and group D streptococcia Downloaded from eurheartj.65 years or with impaired renal function. Preferred in patients .org by guest on August 31.oxfordjournals. pre-dose (trough) concentrations should be .1 mg/L and post-dose (peak.

1 mg/L and post-dose (peak. Rifampin is believed to play a special role in prosthetic device infection because it helps eradicate bacteria attached to foreign material. 1 h after injection) concentrations should be between 3– 4 mg/L.2386 ESC Guidelines Staphylococcus aureus and coagulase-negative staphylococci Staphylococcus aureus is usually responsible for acute and destructive IE. 2010 The clinical benefit of gentamicin addition has not been formally demonstrated.130. whereas CNS produce more protracted valve infections (except S.oxfordjournals. capitis). pre-dose (trough) concentrations should be . d Rifampin increases the hepatic metabolism of warfarin and other drugs. Paediatric doses should not exceed adult doses.131 Table 14 summarizes treatment recommendations for methicillinsusceptible and methicillin-resistant S. the benefit of additional Table 14 Antibiotic treatment of infective endocarditis due to Staphylococcus spp. it remains recommended for PVE. Of note.org by guest on August 31.135 Rifampin should always be used in combination with another effective antistaphylococcal drug. lugdunensis and some cases of S.112 b a . Downloaded from eurheartj. to minimize the risk of resistant mutant selection. c Serum vancomycin concentrations should achieve 25 –30 mg/L at pre-dose (trough) levels. When given in three divided doses. Renal function and serum gentamicin concentrations should be monitored once/week (twice/week in patients with renal failure). Its use is associated with increased toxicity and is therefore optional. e Although the clinical benefit of gentamicin has not been demonstrated. aureus and CNS in both native and prosthetic valve IE.

Gram-negative bacteria 1. vancomycin-intermediate S. quinupristin – dalfopristin with or without b-lactams.8%) of IE cases.152 Treatment options are summarized in Table 16. and tigecycline. and are associated with IE treatment failures. and vancomycin.138 Moreover. First. Enterococcus spp. these conditions should be managed with the input of an infectious diseases specialist.147 This option might be considered in cases where prolonged treatment is limited by toxicity.ESC Guidelines 2387 since MICs are 2 – 4 times lower.139 Observational studies suggest that daptomycin might also be considered in leftsided IE and may overcome methicillin and vancomycin resistance. other third-generation cephalosporins. by Enterococcus faecium or other species.141 Other choices include newer b-lactams with relatively good PBP2A affinity. but with subpopulations growing at higher concentrations) have emerged worldwide.45%)134 and often requires early valve replacement. Enterococcal IE is primarily caused by Enterococcus faecalis (90% of cases) and. However. or 1000 mg/day orally) is a less well validated option. aureus bacteraemia and right-sided IE. 2010 Methicillin-resistant and vancomycin-resistant staphylococci MRSA produce low-affinity plasma-binding protein (PBP) 2A. enterococci are highly tolerant to antibiotic-induced killing.153 . Some HACEK group bacilli produce b-lactamases.org by guest on August 31. Varying results have been reported with quinupristin–dalfopristin. but these regimens are invalid for left-sided IE. and aminoglycosides should not be used in such conditions. b-lactams (via PBP5 modification and sometimes b-lactamases). and the addition of rifampin.146 An aminoglycoside MIC . and recommended for the first 2 weeks in PVE. Otherwise. Again. Streptomycin may remain active in such cases and is a useful alternative.140 However. Conversely.151 Recommended treatment is early surgery plus long-term (!6 weeks) therapy with bactericidal combinations of b-lactams and aminoglycosides. aminoglycoside in S.142. One study reported success with shortcourse administration of aminoglycosides (2 – 3 weeks) in 74 (81%) of 91 episodes of enterococcal IE.136 Although the level of evidence is poor. Importantly. Secondly. adding rifampin in the treatment of staphylococcal PVE is standard practice. Prolonged courses of gentamicin require regular monitoring of serum drug levels and renal and vestibular function. linezolid. Ciprofloxacin (2 Â 400 mg/day i. Non-HACEK species The International Collaboration on Endocarditis (ICE) reported non-HACEK Gram-negative bacteria in 49/2761 (1. Use of the latter is based on its success in treatment of infected orthopaedic prostheses135 (in combination with quinolones) and in the prevention of re-infection of vascular prostheses. sometimes with additional quinolones or cotrimoxazole. prolonged additional use of aminoglycosides. Because of their rarity and severity.150 2. Staphylococcus aureus PVE carries a very high risk of mortality (. New lipopeptide daptomycin (6 mg/kg/day i. Because they grow slowly. daptomycin needs to be administered in appropriate doses to avoid further resistance. High-level gentamicin resistance is frequent in both E. Since dual resistance is rare. and drug interactions. faecalis is the combination of ampicillin and ceftriaxone. Short-term (2 week) and oral treatment have been proposed for uncomplicated rightsided IE (see also Section L).v. and quinolones—the standard treatment is ceftriaxone 2 g/day for 4 weeks. they are susceptible to ceftriaxone. If they do not produce b-lactamase. they may be resistant to multiple drugs. including aminoglycosides. which confers cross-resistance to most b-lactams.145 Such cases warrant collaborative management with an infectious diseases specialist.146 Fully penicillin-susceptible strains (penicillin MIC 8 mg/L) are treated with penicillin G or ampicillin (or amoxicillin) combined with gentamicin.500 mg/L is associated with loss of bactericidal synergism with cell wall inhibitors. aureus IE is not formally demonstrated.oxfordjournals. more prolonged courses of b-lactams or vancomycin should be considered. standard MIC tests may be difficult to interpret. aureus have been isolated from infected patients in recent years. some highly vancomycinresistant S. They are usually resistant to multiple antibiotics. b-lactam might be used against vancomycin-resistant strains and vice versa.148 which synergize by inhibiting complementary PBPs. these situations require the expertise of an infectious diseases specialist. faecalis and E. in four or six doses) plus gentamicin (3 mg/kg/ day divided in two or three doses) for 4 weeks is an option.) was recently approved for S. A further recently described option against gentamicin-resistant E. requiring new approaches to treatment.v. although treatment may be associated with microbial resistance. aureus (VISA) (MIC 4 – 16 mg/L) and hetero-VISA (MIC 2 mg/L. faecium.132.133 It is optional for the first 3 – 5 days of therapy in NVE.137 Downloaded from eurheartj. leaving only vancomycin to treat severe infections. daptomycin.144 and b-lactams plus vancomycin. intravenous ampicillin (12 g/day i.139.143 b-lactams plus oxazolidinones. b-Lactam and vancomycin resistance are mainly observed in E. Other differences in comparison with NVE include the overall duration of therapy. hepatotoxicity. faecium. HACEK-related species HACEK Gram-negative bacilli are fastidious organisms needing specialized investigations (see also Section C). and ampicillin is therefore no longer the first-line option.v. They pose two major problems. and eradication requires prolonged administration (up to 6 weeks) of synergistic bactericidal combinations of cell wall inhibitors with aminoglycosides (Table 15). definitive studies are missing. In vitro bactericidal tests and monitoring of serum antibiotic concentrations may be helpful.149. more rarely. Ampicillin (or amoxicillin) might be preferred Blood culture-negative infective endocarditis The main causes of BCNIE are summarized in Section F.

d 6-week therapy recommended for patients with . C) (monitor haematological toxicity).5 mg/kg/day for !8 weeks (IIa. (ii) quinupristin–dafopristin 3 Â 7. c Multiresistance to aminoglycosides. Three sets of blood cultures should be drawn at 30 min intervals before initiation of . and treatment necessitates dual antifungal administration and valve replacement.50%). Downloaded from eurheartj. replace ampicillin with ampicillin –sulbactam or amoxicillin with amoxicillin –clavulanate (I. replace gentamicin with streptomycin 15 mg/kg/day in two equally divided doses (I. predominate. Candida and Aspergillus spp.154 Most cases are treated with various forms of amphotericin B with or without azoles.2388 ESC Guidelines Table 15 Antibiotic treatment of infective endocarditis due to Enterococcus spp. e Monitor serum levels of aminoglycosides and renal function as indicated in Table 13.v. NVE and late PVE regimens should cover staphylococci. the latter resulting in BCNIE. if so. b b-Lactam resistance: (i) if due to b-lactamase production. f Paediatric doses should not exceed adult doses. Empirical therapy Treatment of IE should be started promptly. C). Suggested regimens are summarized in Table 17.155. late PVE) and (iii) knowledge of local epidemiology. use more prolonged course of b-lactam therapy. antibiotics.org by guest on August 31. 2010 High level resistance to gentamicin (MIC . C). (iii) b-lactam combinations including imipenem plus ampicillin or ceftriaxone plus ampicillin for !8 weeks (IIb. C). g In b-lactam allergic patients. HACEK species. faecalis 148 (IIa.156 Suppressive treatment with oral azoles is often maintained long term and sometimes for life. a Fungi Fungi are most frequently observed in PVE and in IE affecting IVDAs and immunocompromised patients.3 months symptoms and in PVE. although recent case reports describe successful therapy with the new echinocandin caspofungin. especially for antibiotic resistance and specific genuine culture-negative pathogens (Table 16). and vancomycin: suggested alternatives are (i) linezolid 2 Â 600 mg/day i.500 mg/L): if susceptible to streptomycin. (ii) if due to PBP5 alteration. Mortality is very high (. when surgery was performed (early vs. Early PVE regimens should cover methicillin-resistant staphylococci and ideally non-HACEK Gramnegative pathogens. and Bartonella spp. or orally for !8 weeks (IIa.157 The initial choice of empirical treatment depends on several considerations: (i) whether the patient has received prior antibiotic therapy or not (ii) whether the infection affects a native valve or a prosthesis (and. b-lactams. Monitor serum vancomycin concentrations as indicated in Table 13.oxfordjournals. use vancomycin-based regimens. Otherwise. B). A). streptococci. The combination of ampicillin with ceftriaxone was recently suggested for gentamicin-resistant E.

c Doxycycline plus hydroxychloroquine (with monitoring of serum hydroxychloroquine levels) is superior to doxycycline alone and to doxycycline þ fluoroquinolone.158 For IE.oxfordjournals. perivalvular abscesses. it should be used to consolidate antimicrobial therapy once critical infection-related complications are under control (e.161 . Under these conditions.153 Due to the lack of large series. Two different phases may be separated during the course of antibiotic therapy—a first critical phase (the first 2 weeks of therapy). f Treatment of Whipple IE remains highly empirical.159 Logistic issues are critical and require patient and staff education to enforce compliance. OPAT performs equally well independently of the pathogen and clinical context.160. b Addition of streptomycin (15 mg/kg/24 h in two doses) for the first few weeks is optional. doxycycline. and quinolones. Legionella spp. vancomycin. including aminopenicillins and cephalosporins combined with aminoglycosides. Dosages are as for streptococcal and enterococcal IE (Tables 13 and 15). and stroke). and a second continuation phase (beyond 2 weeks therapy) where OPAT may be feasible.. during which OPAT has a restricted indication.1 year) cotrimoxazole therapy.g. d Several therapeutic regimens were reported.383. g-Interferon plays a protective role in intracellular infections and has been proposed as adjuvant therapy in Whipple’s disease. optimal duration of treatment of IE due to these pathogens is unknown. septic emboli.385. monitoring of efficacy and adverse effects. the patient should be directed towards informed medical staff familiar with the case and not an anonymous emergency department. and Chlamydia spp. Table 18 summarizes the salient questions to address when considering OPAT for IE.386 a Outpatient parenteral antibiotic therapy for infective endocarditis Outpatient parenteral antibiotic therapy (OPAT) is used in . If problems arise..ESC Guidelines 2389 Table 16 Antibiotic treatment of blood culture-negative infective endocarditis Downloaded from eurheartj. 2010 Adapted from Brouqui and Raoult. Successes have been reported with long-term (. The presented durations are based on selected case reports. and easy access to medical advice. paramedic and social support.250 000 patients/year in the USA.384 e Newer fluoroquinolones are more potent than ciprofloxacin against intracellular pathogens such as Mycoplasma spp.org by guest on August 31. acute heart failure.

oxfordjournals.2390 ESC Guidelines Table 17 Proposed antibiotic regimens for initial empirical treatment of infective endocarditis. Table 18 Criteria which determine suitability of outpatient parenteral antibiotic therapy (OPAT) for infective endocarditis Adapted from Andrews and von Reyn. (before or without pathogen identification) Downloaded from eurheartj.b Monitoring of gentamicin and vancomycin dosages is as in Table 13 and Table 14.org by guest on August 31. 2010 a.159 .

and prevention of embolic events (Table 19).165 In some cases. surgical therapy during the active phase of the disease is associated with significant risk. Level of evidence. while the patient is still receiving antibiotic treatment. surgery needs to be performed on an emergency (within 24 h) or urgent (within a few days) basis.165. Complications and indications for surgery in left-sided native valve infective endocarditis Part 1. In other cases. Surgery is justified in patients with high-risk features which make the possibility of cure with antibiotic treatment unlikely and who do not have co-morbid conditions or complications which make the prospect of recovery remote.org by guest on August 31.7 HF can be caused by severe aortic or mitral insufficiency. elective surgery: after at least 1 or 2 weeks of antibiotic therapy. the need for surgery will be determined by a combination of several high-risk features. 2010 Table 19 Indications and timing of surgery in left-sided native valve infective endocarditis Class of recommendation.79 Reasons to consider early surgery in the active phase.7. i. Indications and optimal timing of surgery Surgical treatment is used in approximately half of patients with IE because of severe complications. urgent surgery: within a few days. b a .167 The three main indications for early surgery in IE are HF.166 Early consultation with a cardiac surgeon is recommended in order to determine the best therapeutic approach.oxfordjournals. *Emergency surgery: surgery performed within 24 h. are to avoid progressive HF and irreversible structural damage caused by severe infection and to prevent systemic embolism. # Surgery may be preferred if procedure preserving the native valve is feasible.79 HF is observed in 50 –60% of cases overall and is more often present when IE affects the aortic (29%) rather than the mitral (20%) valve.e.162 – 165 On the other hand. surgery can be postponed to allow 1 or 2 weeks of antibiotic treatment under careful clinical and echocardiographic observation before an elective surgical procedure is performed.ESC Guidelines 2391 of patients requiring early surgery is frequently difficult. Each case must be individualized and all factors associated with increased risk identified at the time of diagnosis. irrespective of the duration of antibiotic treatment. I.98. uncontrolled infection. Age per se is not a contraindication to surgery. Identification Heart failure 1. Frequently. intracardiac Downloaded from eurheartj. Heart failure in infective endocarditis HF is the most frequent complication of IE and represents the most frequent indication for surgery in IE.

pulmonary oedema.177.182 In aortic IE.7–10 days). Persisting infection Persisting fever is a frequent problem observed during treatment of IE.178. perivalvular extension occurs most frequently in the mitral –aortic intervalvular fibrosa. intracardiac fistulae. Perivalvular complications include abscess formation. Persisting fever may be related to several reasons.178 Perivalvular abscess is more common in aortic IE (10–40% in native valve IE)3.7.74 Downloaded from eurheartj.6%. particularly in aortic IE. starting with aortic root wall thickening and extending to the development of fistulae. while the sensitivity of TTE is . or by valve obstruction caused by vegetations. perivalvular extension is frequently discovered on a systematic TEE.165 Surgery is indicated in patients with HF caused by severe aortic or mitral insufficiency. Echocardiography is also of more general value for haemodynamic assessment of valvular dysfunction.175 2. the most important risk factors for perivalvular complications were prosthetic valve. Valve perforation.174.185 – 188 The frequency of fistula formation in IE has been reported to be 1. and assessment and monitoring of left ventricular systolic function and left and right heart filling pressures. and research for intracardiac or extracardiac focus of infection. when patients are in persistent pulmonary oedema or cardiogenic shock despite medical therapy. and fistulae (Table 9).171. or.177. aureus being the most commonly associated organism (46%).68. Chamber size is usually normal. secondary mitral lesions. In IE with acute regurgitation. Resultant aneurysm formation on the atrial aspect of the mitral leaflet may later lead to mitral perforation. Surgery should be subsequently considered after healing of IE. Unless severe co-morbidity exists. third degree atrioventricular block. and cardiogenic shock. Perivalvular extension in infective endocarditis Perivalvular extension of IE is the most frequent cause of uncontrolled infection and is associated with poor prognosis and high likelihood of need for surgery. 2. An ECG should therefore be performed frequently during follow-up. Surgery must be performed on an emergency basis.org by guest on August 31. Uncontrolled infection Uncontrolled infection is the second most frequent cause for surgery79 and encompasses persisting infection (.188 Despite high rates of surgery in this population (87%). and infection with CNS. or moderate or severe pulmonary hypertension. regurgitant flow velocities are frequently low with a short deceleration time since pressures in the left atrium (mitral regurgitation) or left ventricle (aortic regurgitation) equalize rapidly. Clinical presentation of HF may include severe dyspnoea.3 Management of persisting fever includes replacement of intravenous lines. Usually. irrespective of the status of infection. when a large vegetation partially obstructs the valve orifice. leaflet perforation. and locally uncontrolled infection.176 In summary. even using TEE. HF is the most frequent and severe complication of IE. In patients with well tolerated severe valvular insufficiency and no other reasons for surgery. aortic location. high left atrial pressure. measurement of pulmonary artery pressure. blood cultures and echocardiography. embolic complications or extracardiac site of infection.170 The suspicion of valve obstruction is raised by an elevated transvalvular gradient on TTE.oxfordjournals.169. infected lines. resistant organisms. Indeed. S. The most characteristic lesion leading to HF in NVE is valve destruction causing acute regurgitation. infection due to resistant organisms. However.179 – 181 and very frequent in PVE (56–100%).107. leaflet rupture (flail leaflet). depending on tolerance of the valve lesion and according to the recommendations of the ESC Guidelines on the Management of Valvular Heart Disease. and two-thirds of these cases occur during the active phase of the disease. perivalvular abscesses are usually located posteriorly or laterally. temperature normalizes within 5– 10 days under specific antibiotic therapy.7 In mitral IE. more rarely. medical management with antibiotics is recommended under strict clinical and echocardiographic observation.3.183 Serial echocardiographic studies have shown that abscess formation is a dynamic process.184 In one study.172 Brain natriuretic peptide (NT-proBNP) has potential use in the diagnosis and monitoring of HF in IE.173 HF may progress from mild to severe during treatment. Indications and timing of surgery in the presence of heart failure in infective endocarditis (Table 19) The presence of HF indicates surgery in the majority of patients with IE7 and is the principal indication for urgent surgery. including inadequate antibiotic therapy. by valve obstruction. or interference of the vegetation mass with leaflet closure. pseudoaneurysms.50%179 – 183 (see Section F). 2010 . small abscesses can be missed. 1. TEE is the technique of choice for the diagnosis and follow-up of all perivalvular complications.181 Pseudoaneurysms and fistulae are severe complications of IE and frequently associated with very severe valvular and perivalvular damage. It must be performed on an urgent basis when HF is less severe. particularly those in a mitral location when there is co-existent annular calcification. Surgery is also indicated in patients with severe acute aortic or mitral regurgitation without clinical HF but with echocardiographic signs of elevated left ventricular enddiastolic pressure (premature closure of the mitral valve). ESC Guidelines the presence of HF indicates early surgery in patients with NVE. repeat laboratory measurements. TTE is of crucial importance for initial evaluation and follow-up. hospital mortality remains high (41%). A special situation is secondary infection168 of the anterior mitral leaflet associated with primary aortic IE with aortic regurgitation. and adverse reaction to antibiotics. In addition to clinical findings. locally uncontrolled infection.92 which may occur as a result of mitral chordal rupture. and acute coronary syndrome.186 – 188 Other complications due to major extension of infection are less frequent and may include ventricular septal defect. and aneurysms are best assessed using TEE.189 Perivalvular extension should be suspected in cases with persistent unexplained fever or new atrioventricular block.7 Moderate-to-severe HF is the most important predictor of in-hospital and 6-month mortality.98.2392 fistulae.

16.186. Overall embolic risk is very high in IE.207 particular microorganisms (staphylococci.79 but was rarely the only reason. abscess).154.68 In the absence of embolism. Thus.195 The best means to reduce the risk of an embolic event is the prompt institution of appropriate antibiotic therapy. uncontrolled infection is most frequently related to perivalvular extension or ‘difficult-to-treat’ organisms. The brain and spleen are the most frequent sites of embolism in left-sided IE. previous embolism. and surgery is recommended as soon as possible. and can be diagnosed by non-invasive imaging.8/1000 patient days in the first week of therapy. Signs of locally uncontrolled infection These include increasing vegetation size. Infection by microorganisms infrequently cured by antimicrobial therapy Surgery is indicated in fungal IE. contrast media should be used with caution in patients with renal failure or haemodynamic instability because of the risk of worsening renal impairment in combination with antibiotic nephrotoxicity.org by guest on August 31. surgery is indicated if a favourable early response to antibiotics is not achieved. according to the probability of conservative surgery.155 Surgery is indicated in IE due to multiresistant organisms.68. the size and mobility of the vegetations are the most potent independent predictors of a new embolic event. . Predicting the risk of embolism Echocardiography plays a key role in predicting embolic events.200 A recent study from the ICE group204 demonstrated that the incidence of stroke in patients receiving appropriate antimicrobial therapy was 4. Several factors are associated with increased risk of embolism.195 Thus.68 Patients with vegetations length .194 Conversely. MRSA or vancomycin-resistant enterococci. 3.200 It must be re-emphasized that the risk of new embolism is highest during the first days following initiation of antibiotic therapy and rapidly decreases thereafter.10 mm) following one or more clinical or silent embolic events despite appropriate antibiotic therapy. Stroke is a severe complication and is associated with increased morbidity and mortality. aureus.208 Candida spp. other complications of IE. when embolic risk peaks.165 The overall benefits of surgery should be weighed against the operative risk and must consider the clinical status and co-morbidity of the patient. In the Euro Heart Survey.).199 – 203 the increasing or decreasing size of the vegetation under antibiotic therapy.195 – 203 However. while pulmonary embolism is frequent in native right-sided and pacemaker lead IE.200. falling to 1. e.193 In summary.195.7–10 days) despite an appropriate antibiotic regimen and when extracardiac abscesses (splenic.199 and biological markers. particularly beyond 2 weeks. In NVE caused by S. surgery is indicated in patients with large vegetations (.68 Surgery undertaken for the prevention of embolism must be performed very early. cerebral.15 mm) and mobile vegetations.196. the size and mobility of the vegetation.199 – 207 the location of the vegetation on the mitral valve. the decision to operate early for prevention of embolism must take into account the presence of previous embolic events. Embolic events in infective endocarditis Embolic events are a frequent and life-threatening complication of IE related to the migration of cardiac vegetations. systematic abdominal and cerebral CT scan may be helpful.134.213 The exact role of early surgery in preventing embolic events remains controversial. false aneurysms or the creation of fistulae.196.10 mm).10 mm are at higher risk of embolism. Surgery is indicated when fever and positive blood cultures persist for several days (. persistent infection despite appropriate antibiotic therapy. Unless severe co-morbidity exists. including the size and mobility of vegetations. Indications and timing of surgery in the presence of uncontrolled infection in infective endocarditis (Table 19) Persistent infection In some cases of IE. Surgery may be considered in patients with very large (. the benefits of surgery to prevent embolism are greatest during the first week of antibiotic therapy. Indications and timing of surgery to prevent embolism in infective endocarditis (Table 19) Avoiding embolic events is difficult since the majority occur before admission.192. the presence of a large vegetation favours earlier surgery. Downloaded from eurheartj. The main indications and timing of surgery to prevent embolism in NVE are given in Table 19. 2010 Prevention of systemic embolism 1. when there are no other reasons for surgery and fever is easily controlled with antibiotics.200 – 205 although prediction remains difficult in the individual patient.ESC Guidelines 2393 2. or renal) and other causes of fever have been excluded. the risk of new events (occurring after initiation of antibiotic therapy) is only 6–21%.211. and the duration of antibiotic therapy.15 mm) isolated vegetations on the aortic or mitral valve.191 Persistent fever is also usually present. during the first few days following initiation 3.195 Whilst promising.204. the presence of locally uncontrolled infection indicates early surgery in patients with NVE.195.212 the addition of antiplatelet therapy did not reduce the risk of embolism in the only published randomized study. especially in staphylococcal IE affecting the mitral valve. However.209 Among these.200 Streptococcus bovis.203 and this risk is even higher in patients with very large (. the likelihood of conservative surgery. antibiotics alone are insufficient to eradicate the infection.190. and other predictors of a complicated course (HF. The value of early surgery in this situation has never been proven. and also in the rare infections caused by Gramnegative bacteria. abscess formation.g.7/1000 patient days in the second week and further thereafter. small abscesses or false aneurysms can be treated conservatively under close clinical and echocardiographic follow-up.68.210 although some risk persists indefinitely whilst vegetations remain present.200. especially those affecting the splenic or cerebral circulation.68. Rarely.68. embolic events may be totally silent in 20% of patients with IE.oxfordjournals. with embolic events occurring in 20 –50% of patients. Surgery is indicated in patients with large vegetations (. In these situations. For this reason. particularly if the vegetation is located on the mitral valve. vertebral. vegetation size was one of the reasons for surgery in 54% of patients with NVE and in 25% of those with PVE.200 multivalvular IE. although this decision is more difficult and must be very carefully individualized.

2010 Operative mortality. mortality should be similar to routine valve surgery. replacement of the aortic valve using a mechanical or biological prosthesis is the technique of choice.235.40 years. it must be eradicated prior to cardiac surgical intervention. stroke. operative mortality in IE lies between 5 and 15%. a recent study showed that in-hospital mortality is 15%. as the risk of embolism is highest at this time.230. valve repair is favoured whenever possible. and help in early post-operative follow-up. The use of cryopreserved or sterilized homografts has been suggested to reduce the risk of persistent or recurrent infection. Principles. and stroke. with risks of recurrence and non-infective post-operative valvular dysfunction of 12 and 7%.223 but their application is limited by poor availability and difficulty of the surgical technique. Coronary angiography Coronary angiography is recommended according to the ESC Guidelines on the Management of Valvular Heart Disease176 in men . HF. assess the result. and immediate results of surgery Pre. and in patients with at least one cardiovascular risk factor or a history of coronary artery disease. previous embolism. Exceptions arise when there are large aortic vegetations which may be dislodged during catheterization. 3. and post-operative complications Peri-operative mortality and morbidity vary according to the type of infective agent.231 A monoblock aorto-mitral homograft has been suggested as a surgical option for extensive bivalvular IE. methods. The use of foreign . low cardiac output syndrome.219 – 221 The use of mitral valve homografts and pulmonary autografts (Ross procedure) has been suggested. Currently.68.229 In experienced hands.oxfordjournals. pneumonia. although such excellent results may not be matched in non-specialist centres.200 In summary. Governing factors include size and mobility of the vegetation. the extent of destruction of cardiac structures. but larger cavities should be allowed to drain into the pericardium or the circulation. any method to repair or replace the valve may be used. annular. Mechanical and biological prostheses have similar operative mortality. In these situations.and peri-operative management 1.222. in post-menopausal women. successful valve repair can be achieved by experienced teams in up to 80% of patients.233 Downloaded from eurheartj. the Ross procedure may be used in children or adolescents to facilitate growth and in young adults for extended durability.226 – 228 Homografts or stentless xenografts may be preferred in PVE or in cases where there is extensive aortic root destruction with aorto-ventricular discontinuity. mechanical prostheses and xenografts compare favourably. but the main reasons are multiorgan failure.215.176 2. embolism is very frequent in IE. high-resolution CT may be used to rule out significant coronary artery disease. In complex cases with locally uncontrolled infection. However. respectively.239 In less complex cases.216 Perforations in a single valve cusp or leaflet may be repaired with an autologous glutaraldehyde-treated or bovine pericardial patch. Small abscesses can be closed directly.218 Residual mitral regurgitation should be assessed using intra-operative TEE. particularly when IE affects the mitral or tricuspid valve.214 material should be kept to a minimum.org by guest on August 31. complicating 20 –50% of cases of IE. where disease is limited to the valve structures alone allowing complete excision of infected tissue. total excision of infected and devitalized tissue should be followed by valve replacement and repair of associated defects to secure valve fixation. Among the most frequent are severe coagulopathy requiring treatment with clotting factors.227.225. intractable sepsis. if necessary. Extracardiac infection If a primary focus of infection likely to be responsible for IE has been identified. coagulopathy. or supraannular tissue defects are preferably repaired with autologous or bovine pericardium.2394 of antibiotic therapy (urgent surgery). or when emergency surgery is necessary.237 Immediate post-operative complications are relatively common. the Task Force does not favour any specific valve substitute but recommends a tailored approach for each individual patient and clinical situation. Risk is increased with large (>10 mm) vegetations and particularly high with very mobile and larger (>15 mm) vegetations. and the patient’s haemodynamic condition at the time of surgery. and atrioventricular block following radical resection of an aortic root abscess with need for pacemaker implantation. The cause of death is often multifactorial. with improved durability. Intra-operative echocardiography Intra-operative TEE is most useful to determine the exact location and extent of infection. Where infection is confined to the valve cusps or leaflets. Mitral subannular. and duration of antibiotic therapy.224. ESC Guidelines Part 2.232 Cardiac transplantation may be considered in extreme cases where repeated operative procedures have failed to eradicate persistent or recurrent PVE. a prosthetic valve then being secured to the reconstructed/reinforced annulus. the degree of left ventricular dysfunction.234 – 239 When surgery must be performed within the first week of antimicrobial therapy. including repair or replacement of the affected valve(s). The choice of technique depends on the vertical extension of the lesion/tissue defect. unless valve surgery is urgent. The risk of embolism is the highest during the first 2 weeks of antibiotic therapy and is clearly related to the size and mobility of the vegetation.225 However. type of microorganism.224.104 Surgical approach and techniques The two primary objectives of surgery are total removal of infected tissues and reconstruction of cardiac morphology. The decision to operate on early to prevent embolism is always difficult and specific for the individual patient. In aortic IE. morbidity. acute renal failure requiring haemodialysis. to guide surgery. falling to 6 –21% after initiation of antibiotic therapy. In mitral valve IE.217 Therefore.237 A pre-operative ECG demonstrating left bundle branch block predicts the need for a post-operative permanent pacemaker. re-exploration of the chest for bleeding or tamponade.

Neurological complications.ESC Guidelines 2395 and can be performed with a relatively low neurological risk (3– 6%) and good probability of complete neurological recovery. CT ¼ computed tomography. abscess. transient ischaemic attack. surgery indicated for HF. 2010 Figure 3 Therapeutic strategy for patients with infective endocarditis and neurological complications. in cases with intracranial haemorrhage. cardiac surgery is not contraindicated unless the neurological prognosis is judged to poor (Figure 3). toxic encephalopathy. Other complications of infective endocarditis Part 1.240 They are associated with an excess mortality. Staphylococcus aureus causes higher overall rates of neurological complications.e.194.org by guest on August 31. silent cerebral embolism. Level of evidence. Evidence regarding the optimal time interval between stroke and cardiac surgery is conflicting because of lack of controlled studies. uncontrolled infection. antithrombotic therapy Neurological complications Neurological events develop in 20–40% of all patients with IE and are mainly the consequence of vegetation embolism. including ischaemic or haemorrhagic stroke.242 If urgent cardiac surgery is needed. close cooperation with the neurosurgical team is mandatory. coma). meningitis. symptomatic or asymptomatic infectious aneurysm. After a neurological event. After an ischaemic stroke. Table 20 and Figure 3 J. particularly in the case of stroke.oxfordjournals.194 and surgery is recommended without delay if an indication remains.240.194 Rapid diagnosis and initiation of appropriate antibiotics are of major importance to prevent a first or recurrent neurological complication. MR ¼ magnetic resonance. or persistent high embolic risk should not be delayed Downloaded from eurheartj.194. neurological prognosis is worse and surgery must be postponed for at least 1 month.194.247 Conversely. A neurologist/neurosurgeon should always be involved in the management of these patients.241 The clinical spectrum of these complications is wide.194 The risk of post-operative neurological deterioration is low after a silent cerebral embolism or transient ischaemic attack. b a .242 – 246 If cerebral haemorrhage has been excluded by cranial CT and neurological damage is not severe (i. Table 20 Management of neurological complications Class of recommendation.98. most patients still have at least one indication for cardiac surgery. brain abscess.246. and seizure.

or after cardiac surgery B Antibiotic toxicity (acute interstitial nephritis).213. Stroke is associated with excess mortality. 2010 summarize the recommended management of neurological complications in IE. aureus PVE and those with a previous neurological event. most patients still have an indication for surgery which is generally not contraindicated. splenic abscess.263 but acute renal failure is often reversible.oxfordjournals. myocarditis. headache. seizures) and imaging should be performed to detect intracranial IAs in any case of IE with neurological symptoms.212.aureus IE. Ruptured IAs have a very poor prognosis. CT and magnetic resonance angiography both reliably diagnose IAs with high sensitivity and specificity.org by guest on August 31. rheumatic complications. Rapid diagnosis and initiation of appropriate antibiotics are of major importance to prevent a first or recurrent neurological complication.261 Causes are often multifactorial:262 B Immune complex and vasculitic glomerulonephritis B Renal infarction B Haemodynamic impairment in cases with HF or severe sepsis. vancomycin (synergistic toxicity with aminoglycosides). and therapy must be tailored to the individual patient.249 – 251 no strong evidence exists on its beneficial effect in clinical practice because of conflicting data. Other complications (infectious aneurysms. Downloaded from eurheartj. No randomized trials exist to guide management.252 from subsequent spread of infection through the intimal vessels. Although initial experimental studies showed a beneficial impact of aspirin therapy on the risk of an embolic event in S. In cases with large. Haemodialysis may be required in some patients.213. To prevent this complication. confusion. After a first neurological event. neurosurgery or endovascular therapy is indicated.254 An intracranial location is most frequent. and the experience of the medical team. Antithrombotic therapy There is no indication for the initiation of antithrombotic drugs (thrombolytic drugs.258 However.248 The recommendations for the management of the anticoagulant therapy are based on low level of evidence (Table 21).257. In patients already taking oral anticoagulants. and the reported frequency of 2 –4% is probably an underestimate since some IAs are clinically silent. Since many unruptured IAs may resolve during antibiotic treatment. pericarditis) Infectious aneurysms Infectious (mycotic) aneurysms (IAs) result from septic arterial embolism to the intraluminal space or vasa vasorum. enlarging. or . neurological events develop in 20 –40% of all patients with IE and are mainly the consequence of embolism. but no predictors of this complication have been identified to date.255 Clinical presentation is highly variable256 (focal neurological deficit. and even high dose penicillin B Nephrotoxicity of contrast agents used for imaging purposes. conventional angiography remains the gold standard and should be performed when non-invasive techniques are negative and suspicion remains. there is a risk of intracranial haemorrhage which seems to be highest in patients with S. anticoagulant or antiplatelet therapy) during the active phase of IE.252 Besides.259 serial imaging is required. or ruptured IAs.2396 ESC Guidelines Table 21 Management of antithrombotic therapy in infective endocarditis a b Class of recommendation.253. acute renal failure.255. antibiotic Part 2. notably related to aminoglycosides. In summary.260 The choice between these options will depend on the presence and size of the haematoma. Acute renal failure Acute renal failure is a common complication of IE which occurs in 30% of patients and predicts poor prognosis. Level of evidence. some studies showed a non-significant increase of major bleeding episodes.

and rheumatic complications may be the first manifestations of the disease. Table 22 Factors associated with an increased rate of relapse .56 When these techniques or the identity of both isolates are unavailable.264 – 266 In one study. back pain) are frequent during IE.269 Myocarditis. suboptimal choice of initial antibiotics. Recurrences: relapses and reinfections The risk of recurrence amongst survivors of IE varies between 2.3 Myocardial involvement is best assessed using TTE. the timing of the second episode of IE may be used to distinguish relapse from reinfection. MRI. an episode of IE caused by the same species within 6 months of the initial episode represents relapse. and a persistent focus of infection (e. myocarditis. and should be performed before valvular surgery unless the latter is urgent. myalgia.oxfordjournals. K. Reinfection is more Downloaded from eurheartj. or bacteraemia often as a result of S. ruptured pseudoaneurysms or fistulae may communicate with the pericardium. need for valve surgery.273 Rheumatic complications Musculoskeletal symptoms (arthralgia. Percutaneous drainage is an alternative for high-risk surgical candidates. whereas later events suggest reinfection. Treatment consists of appropriate antibiotic regimens. HF. pericarditis Cardiac failure may also be due to myocarditis which is frequently associated with abscess formation.275 For these purposes.5%. molecular methods including strain-typing techniques should be employed. Outcome after discharge and long-term prognosis Late complications occurring after the initial infection contribute to the poor prognosis of IE.105.272 Although not systematically differentiated in the literature. Persistent or recurrent fever and bacteraemia suggest the diagnosis. the rate of recurrence in non-IVDAs was 1.56. and these patients should be evaluated by abdominal CT. there is often uncertainty as to whether the repeat infection is a relapse of the initial infection or a new infection (reinfection). Thus. echocardiography may be performed in patients with a definite diagnosis of pyogenic spondylodiscitis and underlying cardiac conditions predisposing to endocarditis. there are two types of recurrence: relapse and reinfection. Prolonged antibiotic therapy is generally required in definite spondylodiscitis. Conversely. periprosthetic abscess). 2010 Splenic abscess Although splenic emboli are common. Imaging with nephrotoxic contrast agents should be avoided in those with haemodynamic impairment or previous renal insufficiency.56 In contrast. Splenectomy may be considered for splenic rupture or large abscesses which respond poorly to antibiotics alone. The term ‘relapse’ refers to a repeat episode of IE caused by the same microorganism as the previous episode. IE was diagnosed in 30.org by guest on August 31.3 Pericarditis may be associated with an abscess.7 and 22.ESC Guidelines 2397 doses should be adjusted for creatinine clearance with careful monitoring of serum levels (aminoglycosides and vancomycin).3.57. the time between episodes is usually shorter for relapse than for reinfection—in broad terms.3. and death.270.272. aureus infection. When the duration of therapy has been insufficient or the choice of antibiotic incorrect. the main complications include recurrence of infection.274 and prophylactic measures should be very strict. Relapses are most often due to insufficient duration of original treatment.235 – 237.g. In these cases. ‘reinfection’ is primarily used to describe infection with a different microorganism. Patients with previous IE are at risk of reinfection. with dramatic and often fatal consequences.268. relapse should be treated for a further 4 –6 weeks depending on the causative microorganism and its susceptibility (remembering that resistance may develop in the meantime).271 Rarely.3% per patient-year. Purulent pericarditis is rare and may necessitate surgical drainage. or ultrasound. Ventricular arrhythmias may indicate myocardial involvement and imply a poor prognosis. Peripheral arthritis occurs in 14% and spondylodiscitis in 3–15% of cases. splenic abscess is rare. storage of endocarditis isolates for at least 1 year is recommended.56 When the same species is isolated during a subsequent episode of IE. although variable.267 MRI or CT of the spine should be performed in IE patients with back pain. Following in-hospital treatment.8% of patients with pyogenic spondylodiscitis and was more common in cases of streptococcal infection and predisposing heart conditions. Regional myocardial infarction may be caused by coronary embolism or compression.56 Factors associated with an increased rate of relapse are listed in Table 22.273 – 275 In a recent large series with mean 5-year follow-up.

while the microbiology of late PVE mirrors that of NVE.275 The type of valve implanted has no effect on the risk of recurrent IE. .236.5% of patients who died.277 in patients undergoing chronic dialysis. Prosthetic valve endocarditis PVE is the most severe form of IE and occurs in 1– 6% of patients with valve prostheses279—an incidence of 0.188.2398 frequent in IVDAs (especially in the year after the initial episode). the infection usually involves the junction between the sewing ring and the annulus. and perforation. Streptococcus bovis. pseudoaneurysms.106. Specific situations Part 1. Preventive measures should be applied in these patients who are a high risk group (see Section E). large vegetations may cause prosthetic valve obstruction.235.2% per patientyear. and HF. 2010 Long-term mortality Long-term survival is 60 –90% at 10 years.273 Following the in-hospital phase. oral streptococci. more probably due to community-acquired infections. Heart failure and need for valvular surgery Progressive HF can occur as a consequence of valve destruction.3.79 and in 20% of 2670 patients with definite IE in the ICE Prospective Cohort Study. Downloaded from eurheartj.280 – 284 It accounts for 10 –30% of all cases of IE280 and affects mechanical and bioprosthetic valves equally. In summary. A negative echocardiogram is frequently observed in PVE2 and does not exclude the diagnosis.278 ESC Guidelines L.225.14 in 26% of cases inthe Euro Heart Survey. blood cultures are more frequently negative in PVE. Similarly. particularly during the first year of follow-up. even when infection is healed.106 PVE is still associated with difficulties in diagnosis.org by guest on August 31.276 in PVE. an initial clinical evaluation and baseline TTE should be performed at the completion of antimicrobial therapy and repeated serially. There is no evidence base to guide the optimal monitoring of these patients.281. principal factors which determine long-term mortality are age.273 Definition and pathophysiology Early PVE is defined as occurring within 1 year of surgery. IE was the cause of the late mortality in only 6. However. its diagnostic value is lower than in NVE. dehiscence. ranging from 3 to 7% in the most recent series.1. including the procurement of blood cultures before empirical use of antibiotics. but whether IE is acquired peri-operatively or not and which microorganism is involved. and 12 months during the first year following completion of treatment. and Gram-negative bacilli are the main causes of early PVE. A survival at 15 –20 years of 50% has been reported. leading to perivalvular abscess. In PVE.105. After completion of treatment. infection is frequently located on the leaflets of the prosthesis. co-morbidity. PVE was observed in 16% of cases in the French Survey.57.273 In a recent series. which can be diagnosed by fluoroscopy and/or TEE. blood samples (white cell count.282 In late PVE.273 and in those with multiple risk factors for IE.273. as compared with NVE. but the Task Force recommend clinical evaluation. the need for late valve surgery is low. recommendations for surgery follow conventional guidelines. For example. and late PVE beyond 1 year.236. in late bioprosthetic PVE.284 However. 3. particularly when surgery has not been performed. because of significant differences between the microbiological profiles observed before and after this time point. fungi. After discharge.285 Although TEE is mandatory in suspected PVE (Figure 1).272. particularly in the early post-operative period.3. determination of the optimal therapeutic strategy. diagnosis of PVE is mainly based on the results of echocardiography and blood cultures. Staphylococci. Diagnosis Diagnosis is more difficult in PVE than in NVE. Less frequently.oxfordjournals. resistant microorganisms.101.235. In cases with perioperative contamination. but may be caused by inadequate initial antibiotic therapy.272. They should be aware that recurrence can occur in IE and that new onset of fever. and enterococci being the most frequent organisms. this is an artificial distinction.1.253. suggesting that long-term mortality is related to the underlying conditions rather than IE itself. C-reactive protein) and TTE at 1.275. Clinical presentation is frequently atypical. and fistulae.106 The pathogenesis of PVE differs according to both the type of contamination and the type of prosthetic valve. To monitor the development of secondary HF.235.274 Information concerning longer follow-up is scarce. both are more frequently negative in PVE. and poor prognosis. persistent focus of infection. leading to vegetations. or other signs of infection mandate immediate evaluation. chills.3 –1. with staphylococci. or intravenous drug abuse. 6. cusp rupture.176 As a consequence of increasing rates of operation during the active phase of the infection. relapse and reinfection are rare following IE.272 Follow-up Patients should be educated about the signs and symptoms of IE after discharge. A recent large prospective multicentre international registry found that 37% of PVE were associated with nosocomial infection or non-nosocomial health care-associated infections in outpatients with extensive health care contact.3 Patients with reinfection are at higher risk of death and need for valve replacement. in which fever and inflammatory syndromes are common in the absence of IE. staphylococcal and fungal infections are more frequent and streptococcal infection less frequent than in NVE. the same and other mechanisms may exist. The consequence of PVE is usually new prosthetic regurgitation.236. patients with IE must be informed of the risk of recurrence and educated about how to diagnose and prevent a new episode of IE. As in NVE.237 Aortic valve and root replacement with a prosthetic conduit yields results comparable with those of homograft root replacement.57. What is important is not the time from the surgical procedure to the onset of IE.

which requires a more prolonged antibiotic regimen (particularly aminoglycosides) and frequent use of rifampin (see Section H). i.oxfordjournals.294. An exception is S.ESC Guidelines 2399 considered in aortic PVE. the best therapeutic option is still debated.13. staphylococcal infection. HF.e. 2010 Table 23 Indications and timing of surgery in prosthetic valve infective endocarditis (PVE) Class of recommendation. including the original prosthesis. patients who are initially treated medically require close follow-up.288 – 290 including age. aureus PVE.285 but are less useful in PVE.134. and any calcium remaining from previous surgery. elective surgery: after at least 1 or 2 weeks of antibiotic therapy. most cases referred for surgery represent uncontrolled PVE and are treated accordingly. Similar data have been reported by others. and these patients need aggressive management. The Duke criteria have been shown to be helpful for the diagnosis of NVE. because of their lower sensitivity in this setting.291 – 295 Although surgery is generally considered the best option when PVE causes severe prosthetic dysfunction or HF. Antimicrobial therapy for PVE is similar to that for NVE. with a sensitivity of 70 –80%.283. Although surgical treatment is frequently necessary in PVE. Among these.291 Conversely. urgent surgery: within a few days. or persistent fever. By definition.283 Although no evidence-based data exist. patients with uncomplicated nonstaphylococcal and non-fungal late PVE can be managed conservatively. or autografts may be Downloaded from eurheartj. severe prosthetic dysfunction. it was performed in only 50% of patients with PVE in the Euro Heart Survey.288. since most are caused by staphylococci or other aggressive organisms. stentless xenografts. and intracardiac abscess. Similarly. Surgery for PVE follows the general principles outlined for NVE. Level of evidence.106. PVE complicated by HF.280 As in NVE. stroke. Radical debridement in these cases means removal of all foreign material. early surgery is frequently needed in early staphylococcal PVE134.org by guest on August 31.279. early PVE. a valved Dacron conduit278 can be used. The need for surgery should be considered in all cases of early PVE. prognostic assessment is of crucial importance in PVE.286. Alternatively. Several factors have been associated with poor prognosis in PVE. since it allows identification of high-risk subgroups of patients in whom an aggressive strategy may be necessary. Homografts. because of the risk of late events. b a . Table 23 summarizes the main indications and proposed timing of surgery in PVE.263. a surgical strategy is recommended for PVE in high-risk subgroups identified by prognostic assessment. *Emergency surgery is surgery performed within 24 h.92.79 similar to patients with NVE. and homograft or xenograft root replacement is indicated for any abnormality of the aortic root that distorts the aortic sinuses. complicated PVE and staphylococcal infection are the most powerful markers.295 However. abscess.287 Prognosis and treatment A very high in-hospital mortality rate of 20 –40% has been reported in PVE.290 or PVE caused by fungi or other highly resistant organisms.283.

297 The consequence may be formation of vegetations. Clinical presentation is frequently misleading.oxfordjournals.305 as well as local signs of infection. Diagnosis is more difficult than in NVE. 2010 Definition and pathophysiology of cardiac device infections. CDRIE must be suspected in the presence of unexplained fever in a patient with a CD. Patients with non-complicated. echocardiography and blood cultures are the cornerstone of diagnosis.302.309 Blood cultures are positive in 77% of cases of CDRIE. differentiating LDI and CDRIE is frequently difficult.299 Both diagnosis and therapeutic strategy are particularly difficult in these patients.297 A recent populationbased study found an incidence of CD infection of 1. However. Septic pulmonary embolism is a very frequent complication of CDRIE. with predominant respiratory or rheumatological symptoms. Fever is frequently blunted. and percutaneous extraction remains the recommended method even in cases of large vegetations.303 Then. CDRIE must be treated by prolonged antibiotic therapy associated with device removal. Other possible mechanisms of CDRIE include haematogenous seeding from a distant focus of infection. or purulent drainage. but also on the mural endocardium of the right atrium and right ventricle.310 Antimicrobial therapy for PPM infections should be individualized and based on culture and susceptibility results if possible.312 CD extraction can be performed percutaneously without need for surgical intervention in the majority of patients. if treated without surgery. sizing of vegetations.302.9 per 1000 device-years and a higher probability of infection after ICD as compared with PPM. As in other forms of IE.305 – 308 and is cost-effective.305 Finally. or endocardial surface. Echocardiography plays a key role in CDRIE and is helpful for the diagnosis of both lead vegetation and tricuspid involvement. in the case of occult infection without any other apparent source than the device. Attempts to treat these patients with antibiotic alone have been proposed in the case of negative TEE. LDI is defined as an infection limited to the pocket of the CD and is clinically suspected in the presence of local signs of inflammation at the generator pocket. aureus being predominant in the acute forms of PPM infection.302 Staphylococci are the most frequent pathogens. non-staphylococcal late PVE can be managed conservatively with close follow-up. including erythema. percutaneous extraction may be more difficult when the CD has been implanted for several years. erosion. However.298 Overall incidence lies between that of NVE in the general population and that of PVE. quantification of tricuspid regurgitation. warmth. However. lung CT and lung scintigraphy are both useful to detect pulmonary septic embolism. it is recommended to perform both in suspected CDRIE. staphylococcal PVE.305 Some authors recommend surgery to be performed in patients with very large vegetations.305 The Duke criteria are difficult to apply in these patients because of lower sensitivity. A distinction should be made between local device infection (LDI) and cardiac device-related IE (CDRIE). is a severe disease associated with high mortality.296 The rising number of patients with an implanted CD explains the increasing frequency of IE in these patients. However.302 For this reason. Complicated PVE.296.300 CDRIE is defined as an infection extending to the electrode leads. In one study. in the case of definite CDRIE.302 The main mechanism of CDRIE is contamination by local bacteriological flora at the time of device implantation. tenderness. on the tricuspid valve.302. Pulmonary embolism as a result of vegetation displacement during extraction occurs frequently.301 culture of intravascular lead segments was positive in 72% of 50 patients with manifestations strictly limited to the implantation site.313 However.311 However. and follow-up after lead extraction. Infective endocarditis on pacemakers and implantable defibrillators Infection of cardiac devices (CDs). the possibility of intra-operative contamination of the lead tip cannot be excluded in these patients. these episodes are frequently asymptomatic. Antibiotic prophylaxis is protective in this indication.314 when percutaneous extraction is technically impossible.304 Diagnosis CDRIE is one of the most difficult forms of IE to diagnose.305. and must be managed aggressively. Part 2. PVE represents 20% of all cases of IE with increasing incidence. medical therapy alone has been associated with high mortality and risk of recurrence. and early reimplantation.313 since overall risks are even higher with surgical extraction.302 It has recently been proposed that positive lead cultures can be used as a sign of CDRIE only in the absence of pocket infection or when the leads were removed using a remote incision from the pocket or surgical extraction. both TTE and TEE may be falsely negative in CDRIE. S.297. cardiac valve leaflets. or when severe tricuspid valve IE is associated. Downloaded from eurheartj. particularly when vegetations are large. Although TEE has superior sensitivity and specificity to TTE. including permanent pacemakers (PPMs) and implantable cardioverter defibrillators (ICDs).296. Modifications of Duke criteria have been proposed. ESC Guidelines implantation. use of temporary pacing before Treatment (Table 24) In the majority of patients. particularly in elderly patients.302. When performed.296.2400 In summary.3 on the electrode lead. wound dehiscence. the infection can spread along the electrode to the endocardium and the electrode tip. Several factors have been associated with CD infections. including fever within 24 h before implantation. fluctuance. The reported incidence of PPM infection varies widely among studies. CD removal is recommended in all cases of proven CDRIE and should also be considered when CRDIE is only suspected. and a normal echographic examination does not rule out CDRIE. Preliminary experience with intracardiac echocardiography has recently been reported. which can be found anywhere from the subclavian vein to the superior vena cava.305 to include local signs of infection and pulmonary embolism as major criteria. surgery requires good exposure under . Duration of therapy should be 4–6 weeks in most cases.org by guest on August 31. and early PVE are associated with worse prognosis.

2010 a b Class of recommendation. right atrium.320 Although it may occur in patients with a PPM. Temporary pacing is not recommended because it has been shown to be a risk factor for subsequent CD infection. and left-sided IE is not . ICD. right ventricular free wall. and distal superior vena cava is essential. epicardial implantation is a possible alternative.14.321 This disease occurs more frequently in IVDAs who are HIV seropositive.322 Damage to the right-sided valves from injected particulate matter associated with poor injection hygiene. but some recent data show an increasing number of hospitalizations for intravenous drug abuse-related IE. Immediate reimplantation should be avoided owing to the risk of new infection.320. Level of evidence.306. Prognosis is poor. mortality associated with surgical removal is high315 in these frequently elderly patients with associated co-morbidities. The exact incidence of IE in IVDAs is unknown. Right-sided infective endocarditis Epidemiology Right-sided IE accounts for 5 –10% of cases of IE. CDRIE must be treated by prolonged antibiotic therapy and device removal. Excision of all infected contact lesions at the level of the tricuspid valve. extracorporeal circulation to allow complete removal of all foreign material. a new transvenous system is usually implanted on the contralateral side. central venous catheter. CDRIE is one of the most difficult forms of IE to diagnose. device extraction may be considered. particularly those with advanced immunosuppression. contaminated drug solutions. and must be suspected in the presence of frequently misleading symptoms. and this decision must be adapted to the individual patient. However. In the majority of patients.300. or CHD.oxfordjournals. pulmonary and eustachian valve infection may also be observed.ESC Guidelines 2401 Table 24 Cardiac device-related infective endocarditis (CDRIE): treatment and prevention Downloaded from eurheartj. Part 3. reassessment may lead to the conclusion that reimplantation is unnecessary in a number of patients.319.316 In patients with NVE or PVE and an apparently non-infected PPM. In other patients. Finally.310. particularly in elderly patients. with reduced infectious risk.317 Although there are no large controlled studies on this topic.org by guest on August 31. antibiotic prophylaxis is usually recommended before implantation. There is no clear recommendation concerning the optimal timing and site of reimplantation. and abnormalities of immune function are some of the pathophysiological hypotheses underlying right-sided IE in IVDAs.304 If reimplantation is performed. this situation is most frequently observed in IVDAs. reimplantation can be postponed for a few days or weeks. If immediate reimplantation is necessary. not least because of its frequent occurrence in elderly patients with associated co-morbidity.318 In summary.323 Whilst the tricuspid valve is the usual site of infection in IVDAs.

(2) valve repair whenever possible.342.org by guest on August 31. vegetations . the choice of initial empiric antimicrobial therapy depends on the suspected microorganism.333. and increased drug clearance in IVDAs. ESC Guidelines Diagnosis and complications The usual manifestations of right-sided IE are persistent fever.20 mm.344.335.347 (d) IVDA with severe immunosuppression (CD4 count . aureus must always be covered. acute renal failure.350 For organisms other than MSSA. Pulmonary septic emboli may be complicated by pulmonary infarction.340.328 Right HF is rare. poor penetration into vegetations. therapy has to be adjusted.339 More conventionally. the standard therapy for IE due to MSSA is appropriate. antibiotic treatment should include cover against streptococci and enterococci.341 There are also consistent data showing that a 2-week treatment may be sufficient341 – 343 and that the addition of an aminoglycoside may be unnecessary.352. and polymicrobial infections also occur less frequently. other Gramnegative organisms. Because of limited bactericidal activity.346. 20 mm vegetation and 3 Absence of severe immunosuppression (. bacteraemia. aureus IE in IVDAs may also be successfully treated with oral ciprofloxacin (750 mg b. a CD4 count of . Although the full implications of HIV infection for the medical and surgical therapy of IE in IVDAS are not yet fully known.g. which may manifest with chest pain.324 – 326 Staphylococcus aureus is the dominant organism (60– 90%).333 – 335 Vegetation length . the type of drug and solvent used by the addict. paradoxical embolism or associated left-sided IE should be considered.i. and the location of cardiac involvement.334 In right-sided NVE.355 Current strategies for surgery of tricuspid valve IE should be based on the following three principles: (1) debridement of the infected area or ‘vegetectomy’. Antimicrobial therapy On admission. S. particularly in IVDAs or venous catheter-related infection.20 mm and fungal aetiology were the main predictors of death in a recent large retrospective cohort of right-sided IE in IVDAs. The standard 4–6 week regimen must be used in the following situations: (a) slow clinical or microbiological response (.343.329 – 331 However.20 mm which persist after recurrent pulmonary emboli with or without concomitant right HF.g. Cardiac surgery in HIV-infected IVDAS with IE does not worsen the prognosis of either the IE or the HIV.322 1.g.337 If the patient is a pentazocine addict.345 Indications for surgery and the peri-operative approach in IVDAS are the same as for non-addicts but should be more conservative overall since IVDAS have a much higher incidence of recurrent IE.i. or haemoptysis.335 In HIV-infected patients.354. e. depending on the local prevalence of MRSA.200 cells/mL has a high prognostic value.351 2. pneumothorax.320. or extracardiac complications.334 Once the causative organisms have been isolated.349 (e) associated left-sided IE. an antipseudomonas agent should be added.348.352 (c) Tricuspid valve vegetations . TEE is more sensitive in the detection of pulmonary vegetations332 and abscesses (particularly those adjacent to the membranous septum). acute respiratory failure. cough. Surgery Surgical treatment should generally be avoided in right-sided native IE. 2010 Prognosis and treatment Prognosis of right-sided NVE is relatively good. in IVDAs with underlying valve lesions and/or left-sided involvement. enterococci.) provided that the strain is fully susceptible to both drugs and patient adherence is monitored carefully.200 CD4 cells/mm3) with or without AIDS.200 cells/mL) with or without AIDS. aeruginosa) despite adequate antimicrobial therapy. 3 Absence of metastatic sites of infection or empyema and 3 Absence of cardiac and extracardiac complications and 3 Absence of associated prosthetic valve or left-sided valve infection and 3 . avoiding artificial material. Treatment will include either penicillinase-resistant penicillins or vancomycin.341 Two-week treatment with oxacillin (or cloxacillin) with or without gentamicin is possible if all the following criteria are fulfilled: 3 Methicillin-susceptible S. therapy in IVDAs does not differ from that in non-addicts. In IVDAs. albicans) should be considered and antifungal treatment added. a 2-week course of antimicrobial therapy is unsuitable. When systemic emboli occur. glycopeptides should not be used in a 2-week treatment. but can be caused by the increase of pulmonary pressures or severe right-sided valvular regurgitation or obstruction.353 usually due to continued drug abuse. with clear data demonstrating that penicillinase-resistant penicillin regimens are superior to glycopeptide-containing regimens. aureus and 3 Good response to treatment and .356 and (3) if valve replacement is Downloaded from eurheartj.2402 unusual in this group. Right-sided S.327.d.96 h) to antibiotic therapy. with an in-hospital mortality rate . streptococci.d. septic metastatic foci outside the lungs (including empyema).327 and Pseudomonas aeruginosa. abscess.oxfordjournals. and purulent pulmonary effusion. or bacteraemia for at least 7 days (e. but should be considered in the following situations (Table 25): (a) right HF secondary to severe tricuspid regurgitation with poor response to diuretic therapy. persistent fungi). fungi. (b) IE caused by organisms which are difficult to eradicate (e. P.336.344 (b) right-sided IE complicated by right HF. Candida spp. (not C.333.345 (c) therapy with antibiotics other than penicillinase-resistant penicillins. aureus. S. and multiple septic pulmonary emboli.344.343.) plus rifampicin (300 mg b.10%.338 If an IVDA uses brown heroin dissolved in lemon juice. and associated left-sided involvement. TTE usually allows assessment of tricuspid involvement because of the anterior location of this valve and usual large vegetations.

each contributing to the total risk of IE. when serious haemodynamic complications arise. Despite relatively low in-hospital mortality. Complex anatomy makes echocardiographic assessment difficult. such as secundum atrial septal defect and pulmonary valve disease.371 Cardiac repair as a secondary preventive measure to reduce the risk of recurrent IE has been described but not systematically studied.363 – 365 with a consistent minor male dominance. However. The superiority of TEE over TTE has not been systematically studied in this setting.org by guest on August 31.360 Pulmonary valve replacement is best avoided—if judged necessary. if unavailable. TTE is of major value in these patients. particularly in patients with elevated pulmonary arterial pressure. complications. right-sided IE is more frequent in CHD than in acquired cardiac disease.58. and skin hygiene has already been emphasized. use of a pulmonary homograft (or. there is also an educational problem. Downloaded from eurheartj.362 The reported proportion of CHD in patients with IE varies. For example. a negative study does not exclude the diagnosis. Prognosis is better than in other forms of IE. right-sided IE is most frequently observed in IVDAs and CHD.366 The principal symptoms.370 However.358 Cryopreserved mitral homografts have been used for management of persistent tricuspid endocarditis.ESC Guidelines 2403 Table 25 Indications for surgical treatment of right-sided infective endocarditis a b Class of recommendation. a xenograft valve) is preferred.364. CHD often consists of multiple cardiac lesions. Diagnostic features include respiratory symptoms and fever. complex anatomy and the presence of artificial material may reduce the rate of detection of vegetations and other features of IE. carry a low risk of IE. Part 4. IE in CHD carries a mortality of 4–10%.367 The distribution of causative organisms does not differ from the pattern found in acquired heart disease. It may be performed in extreme cases. but may be associated with severe post-operative right HF. thus favouring the addition of TEE.366 This better prognosis in comparison with acquired heart disease may reflect the higher proportion of right heart IE. probably due to selection bias.362 However. Preventive measures and patient education are of particular importance in this population.366 Some simple lesions. between 2 and 18%. IE in CHD is rare and more frequently affects the right heart. excision of the tricuspid valve with prosthetic valve replacement.362.58. our knowledge of IE in this setting is limited since systematic studies are few and often retrospective. unavoidable.357 Valvectomy without prosthetic replacement has been advocated.361.369 Cosmetic piercing.g. and when there is a high risk of devastating septic embolism.oxfordjournals.g. right-sided IE has a high risk of recurrence in IVDAs and a conservative approach to surgery is recommended in this group. at least involving the tongue and mucous membranes. with a mortality rate <10%. and basis for diagnosis do not differ from IE in general. Primary prevention is vital.62. after multiple pulmonary emboli. Treatment of IE in CHD follows general principles.58. However. There are no scientific data justifying cardiac surgery or percutaneous interventions (e. The reported incidence of IE in CHD is 15 –140 times higher than that in the general population (the highest estimate originating from a highly specialized unit).362.362. streptococci and staphylococci being the most common strains. dental. and awareness of the risk of IE and need for preventive measures are not satisfactorily spread in the population with CHD. Surgical repair of CHD often reduces the risk of IE. Cardiac surgery is appropriate when medical therapy fails. In summary. the incidence of IE is considerably higher in patients with a ventricular septal defect when there is associated aortic regurgitation. closure of a patent ductus arteriosus) with the sole purpose of eliminating the risk of IE. 2010 . provided there is no residual lesion. and this is the major substrate for IE in younger patients. particularly in the adult group. Level of evidence.359. However. In summary. should be discouraged in this group. and selection bias associated with studies from highly specialized centres hampers universal application.368 The importance of good oral. but the valve should be subsequently replaced once cure of infection has been achieved. e. the procedure may increase the overall risk of IE. Infective endocarditis in congenital heart disease The population of children and adults with CHD is expanding. However. in other cases when artificial valve substitutes are implanted. However. and antibiotic prophylaxis is indicated in high-risk groups as defined in Section E.

oxfordjournals. Oto A. von Graevenitz A. ACC/AHA 2008 Guideline Update on Valvular Heart Disease: Focused Update on Infective Endocarditis. Steckelberg JM.111:e394 –e434. Sandoe JA. bovis IE. Perry JD. Shulman ST.189:301 –302. Gardner T.166. Levison M. Takahashi M.7% of elderly patients with IE. Fernandez Burgos E. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. and high embolic risk.escardio. Gattringer R.382 Downloaded from eurheartj. Smiseth OA. Mazzotta G. Nishimura RA. EBAC works according to the quality standards of the European Accreditation Council for Continuing Medical Education (EACCME). Leyh RG. though not consistently. Burns JC. Habib G. Aldershvile J. Moreillon P. Guidelines on prevention. Vardas P. 2.376 and have been associated with colonic disease.92:124 –130.70 years) is increasingly frequent and associated with specific features. Lytle BW.377 Fever is less frequent374 and anaemia more common in elderly patients. Kramer HH.375 This more severe clinical course has been related to insidious initial symptoms and delayed diagnosis in elderly people. Working Party of the British Society for Antimicrobial C. Jeyasingham MS. Rapid detection of IE and appropriate treatment is important in reducing the risk of both maternal and foetal mortality. Bolger AF. and the Council on Clinical Cardiology. Falace DA. Watkin RW.006%. Dean V.oxfordjournals. Kuhl S. Baltimore RS. Management of infective endocarditis. Ertl G. Leport C. Newburger JW.373 and 33% of patients were older than 67 years in a French registry. Niebel J. Lekakis J. all authors participating in this programme have disclosed potential conflicts of interest that might cause a bias in the article.116:1736 –1754. Block M. Elliott TS. References 1. Takahashi M. Duval X. Fluckiger U.14 Previous reports have shown. Council on Cardiovascular Surgery and Anesthesia. Bonow RO.375 Fewer elderly patients are treated by surgery. Parkhomenko A. O’Rourke RA. Rosenhek R.372. Priori SG.372 The relative incidence of IE affecting the elderly was 26% in the Euro Heart Survey. ¨ . Oto A. Endocarditis. 7. Heart 2005. Moulds RF. Blanc JJ. Peters G. 11. Franzen D. Circulation 2008. Filipatos G. in which colonic lesions are frequent and may cause occult bleeding. bovis) are an increasingly frequent cause of IE. Tani LY. Seifert H. Horstkotte D. 57:1035 –1042. Danchin N. In compliance with EBAC/EACCME guidelines.ehj and European Society of Cardiology http://www. Baddour LM.208 In some studies.org/guidelines. Lode H. multiple valve involvement. Erbel R. Lindahl B. with the same indications as for younger patients. The Organizing Committee is responsible for ensuring that all potential conflicts of interest relevant to the programme are declared to the participants prior to the CME activities. Fowler VG Jr. Council on Cardiovascular Disease in the Young.372. 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Cabell CH.381 The incidence of IE during pregnancy has been reported to be 0. while foetal mortality is 29%. the vegetations in the elderly have been reported to be smaller375 and to carry a lower embolic risk. Endocarditis. 3. Herrmann M. 4. Taubert KA. Shulman ST. Pallasch T. Infective endocarditis during pregnancy A challenge for the physician during pregnancy in the cardiac patient is the changing cardiovascular physiology which can mimic cardiac disease and confuse the clinical picture. Schmaltz AA. Horstkotte D.374. Que YA. and treatment of infective endocarditis (new version 2009)’ is accredited by the European Board for Accreditation in Cardiology (EBAC). CME questions for this article are available at: European Heart Journal http://cme. Goff D.208 Enterococcal IE has also been shown to be more frequent in older patients. ¨ Mugge A. Morais J. Bayer AS. and Kawasaki Disease Committee. Int J Antimicrob Agents 2007.374. Council on Cardiovascular Disease in the Young. Lancet 2004. Med J Aust 2008. Faxon DP. Baumgartner B. Kern P. O’Gara PT. that IE in advanced age is associated with poor prognosis and with a high complication rate.166. Thiene G. Durack DT.382 Therefore. antimicrobial therapy. M. Pavie A. Delahaye F. Vahanian A. 2010 The CME Text ‘Guidelines on the prevention. Lekakis J. Infective endocarditis in the elderly IE in the elderly (. Jaussi A. Lockhart PB. Cowie M.374. Newburger JW. Infective endocarditis: diagnosis. the incidence of IE increased between 1991 and 1999 among patients . especially in the elderly.80 In the French surveys. and Cardiovascular Surgery and Anesthesia.375 A gastrointestinal source of infection has been described more commonly in elderly patients. Heart 2006. Carabello BA.

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