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    4-5 YEARS

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    A Special Reprint of Recruitment Ads

    from the April 25, 2013, Issue

    of the New England Journal of Medicine

    NEJMCareerCenter.org

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    April 25, 2013

    Dear Physician:

    As a physician in your early years of practice, you may be assessing what kind of practice will ultimately be best

    for you. The New England Journal of Medicine is the leading source of information about job openings for physicians in

    the United States. Because we want to assist you in this important search, a complimentary reprint of the classified

    advertising section of the Apri l 25, 2013, issue of NEJM is enclosed.

    The NEJM CareerCenter website (NEJMCareerCenter.org) continues to receive positive feedback from physicians.

    Because the site was designed based on advice from your colleagues, many physicians are comfortable using it for

    their job searches and welcome the confidentiality safeguards that keep personal information and job searches

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    At NEJM CareerCenter, you will find the following: Hundreds of quality, current openings not jobs that were filled months ago

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    A career in medicine is challenging, and current practice leaves little time for keeping up with new information.

    While the New England Journal of Medicines commitment to delivering top-quality research and clinical content remains

    unchanged, we are continually developing new features and enhancements to bring you the best, most relevant

    information each week in a practical and clinically useful format.

    A reprint of the April 11, 2013, article Clinical Practice: Infective Endocarditis, is also included in this booklet.Our popular Clinical Practice articles offer evidence-based reviews of topics relevant to practicing physicians.

    Expanding upon this series, we created Clinical Therapeutics review articles that focus on a specific therapy

    (e.g., medication, device, or procedure) for a given clinical problem.

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    clinical practice

    T h e n e w e n g l a n d j o u r n a l o f medicine

    n engl j med 368;15 nejm.org april 11, 2013

    ThisJournalfeature begins with a case vignette highlighting a common clinical problem.Evidence supporting various strategies is then presented, followed by a review of formal guidelines,

    when they exist. The article ends with the authors clinical recommendations.

    An audio versionof this article isavailable atNEJM.org

    Infective Endocarditis

    Bruno Hoen, M.D., Ph.D., and Xavier Duval, M.D., Ph.D.

    From Service de Maladies Infectieuses etTropicales, Centre Hospitalier RgionalUniversitaire, and Unit Mixte de Recher-che 6249 Chrono-environnement, CentreNational de la Recherche Scientifique,Universit de Franche-Comt, Besanon(B.H.); Association pour lEtude et laPrvention de lEndocardite Infectieuse,Paris (B.H., X.D.); and INSERM Centre

    dInvestigation Clinique 007, AssistancePubliqueHpitaux de Paris, HpitalUniversitaire Bichat, and INSERM Unit738, Universit Paris Diderot, Paris 7,Unit de Formation et de Recherche deMdecineBichat, Bichat (X.D.) all inFrance. Address reprint requests to Dr.Hoen at Service de Maladies Infectieuseset Tropicales, CHRU de Besanon, 25030Besanon CEDEX, France, or at bruno.hoen@univ-fcomte.fr.

    Drs. Hoen and Duval contributed equallyto this article.

    N Engl J Med 2013;368:1425-33.

    DOI: 10.1056/NEJMcp1206782Copyright 2013 Massachusetts Medical Society.

    A 55-year-old man with a history of mitral regurgitation seeks care after an episode oftransient weakness in his right arm and speech difficulties. He underwent dentalscaling 1 month earlier. He notes recent intermittent fevers and weight loss. On cardiacexamination, his regurgitation murmur appears to be unchanged. A transthoracicechocardiogram shows a mobile, 12-mm mitral-valve vegetation and grade 2 (mild)regurgitation. Magnetic resonance imaging of the brain reveals recent ischemic le-sions. How should the patient be further evaluated and treated?

    THE CLINICAL PROBLEM

    Infective endocarditis has an estimated annual incidence of 3 to 9 cases per 100,000persons in industrialized countries.1-7The male:female case ratio is more than 2:1.The highest rates are observed among patients with prosthetic valves, intracardiacdevices, unrepaired cyanotic congenital heart diseases, or a history of infective endo-carditis, although 50% of cases of infective endocarditis develop in patients with noknown history of valve disease. Other risk factors include chronic rheumatic heartdisease (which now accounts for

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    T h e n e w e n g l a n d j o u r n a l o f medicine

    n engl j med 368;15 nejm.org april 11, 2013

    Coxiella burnetii(the agent causing Q fever), bacte-ria in the HACEK group (haemophilus species,Aggregatibacter [formerly Actinobacillus] actinomy-cetemcomitans, Cardiobacterium hominis, Eikenella cor-rodens, and Kingella kingae), and Tropheryma whip-plei.6,10,11

    PATHOGENESIS

    Normal valvular endothelium is naturally resistantto colonization by bacteria. In the conventionalmodel of native-valve infectious endocarditis, in-fection results from the colonization of damagedvalvular endothelium by circulating bacteria withspecific adherence properties. Endothelial dam-age may result from so-called jet lesions due toturbulent blood f low or may be provoked by elec-trodes or catheters or by repeated intravenous in-jections of solid particles in intravenous-drug users.Chronic inf lammation, as in chronic rheumaticheart disease and degenerative valvular lesions,12may also promote infective endocarditis. How-ever, the conventional model may not accuratelyexplain the pathogenesis of infective endocardi-tis due to intracellular microorganisms, such asC. burnetii, bartonella species, or T. whippelii, in which

    the exposure and immune response of the host mayplay a prominent role.13

    CLASSIFICATION

    Whereas infective endocarditis was previously clas-sified according to its mode of presentation (acute,subacute, or chronic), it is now categorized accord-ing to underlying cardiac conditions, location,the presence of intracardiac devices, or the modeof acquisition. These classif ications overlap, withsome cases of infective endocarditis belonging to

    more than one group. Table 1 in the Supplemen-tary Appendix shows the distribution of cases

    among these categories and the correspondingmicroorganisms.

    OUTCOMES

    In contemporary population-based studies of in-fective endocarditis in industrialized countries, in-hospital mortality ranges from 15 to 22%,5,7and5-year mortality is approximately 40%.14How-ever, rates vary widely across subgroups of pa-tients. For instance, in-hospital mortality is lessthan 10% among patients with right-sided lesionsor oral streptococcal, left-sided, native-valve le-sions, whereas it is 40% or more among patientswith prosthetic-valve infective endocarditis dueto Staphylococcus aureus. In a multivariate analysisassessing risk factors for death among patientswith infective endocarditis, independent predic-tors included higher age, S. aureusinfection, heartfailure, cerebrovascular and embolic events, andhealth careassociated infective endocarditis.5,7

    STR ATEGIES AND EVIDENCE

    PRESENTATION AND DIAGNOSIS

    The diagnosis of infective endocarditis is generallybased on clinical, microbiologic, and echocar-diographic findings. The Duke criteria (Table 1)have sensitivity and specificity of more than 80%and are the reference criteria for diagnosis.15However, they should not replace clinical judg-ment for diagnosis in the individual patient, es-pecially in the first stage of care.

    Fever is common, occurring in 80% of cases.6,7In large, contemporary case series, recognition of

    key Clinical points

    infective endocarditis

    Staphylococci and streptococci account for 80% of cases of infective endocarditis, with staphylococci currently the most

    common pathogens.

    Cerebral complications are the most frequent and most severe extracardiac complications. Vegetations that are large, mo-

    bile, or in the mitral position and infective endocarditis due to Staphylococcus