Cardiac complications include congestive heart failure, new or progressive valvular dysfunction that is usually seen as increased regurgitation, periannular extension of infection, sinus of Valsalva rupture, myocardial dysfunction, obstruction of conduits or shunts, prosthetic valve dysfunction including dehiscence, pericardial effusion, and less commonly, septic emboli to the coronary arteries. Congestive heart failure is caused by various combinations of the above factors and is one of the more frequent complica- tions that carries a guarded prognosis. Progressive congestive heart failure usually is caused by worsening valvular regur- gitation, often accompanied by ventricular dysfunction. Poor ventricular function is associated with an increased surgical Urgent surgery in patients with moderate to severe heart failure improves the likelihood of survival and preservation of cardiac function.137 In general, for patients with IE, the degree of illness is not considered a limitation to surgical intervention because the alternative, to delay or defer surgery, can have dire consequences. Periannular extension of infection also increases the risk of congestive heart failure.138,139 The greatest risk for this complication exists in aortic valve endocarditis. Periannular infections also cause fistulous tracks into the pericardium, as well as between cardiac chambers or vascular structures. Such abscesses or fistulae usually do not respond to medi- cal management alone and require surgical treatment. Sinus of Valsalva aneurysms may occur with rupture into any of the cardiac chambers.140 Clinical signs and symptoms of extension of infection beyond valve leaflets are nonspe- cific and include persistent bacteremia or fever, recurrent emboli, heart block, worsening congestive heart failure, or new pathological murmurs in patients receiving appropriate Surgicallycreatedshuntsorintracardiacconduitsareapoten- tial source for complications of IE. Because these connections Table 8. Empirical Therapy in Culture-Negative Endocarditis* Regimen Dosage and Route Duration, wk Strength of Recommendation (Class/LOE) Comments Native valve Ampicillin-sulbactam 12 g/d IV in 4 equally divided doses 4 6 IIb/C Consensus of experts is that patients with culture-negative endocarditis should be managed with consultation with an infectious diseases specialist plus IV/IM in 3 equally divided doses 4 6 IV in 2 equally divided doses 4 6 IIb/C Vancomycin is recommended only for patients who are unable to tolerate penicillins plus IV/IM in 3 equally divided doses 4 6 plus ciprofloxacin 1500 mg/d PO or 800 mg/d IV in 2 equally divided doses Pediatric dosage: Ampicillin-sulbactam 300 IV in 4 6 equally divided doses; IV/IM in 3 equally divided doses; vancomycin 40 mg kg 1 or 3 equally divided doses; ciprofloxacin 20 30 IV/PO in 2 equally divided doses Prosthetic valve (early, 1 y) IV in 2 equally divided doses 6 IIb/C plus IV/IM in 3 equally divided doses 2 plus cefepime 6 g/d IV in 3 equally divided doses 6 plus rifampin 900 mg/d PO/IV in 3 equally divided doses 6 Pediatric dosage: Vancomycin 40 mg kg 1 IV in 2 or 3 equally divided doses; gentamicin IV/IM in 3 equally divided doses; IV in 3 equally divided PO/IV in 3 equally divided doses Prosthetic valve (late, >1 y) 6 IIb/C Same regimens as listed above for native valve endocarditis Suspected Bartonella, culture negative Ceftriaxone sodium 2 g/d IV/IM in 1 dose 6 IIa/B Patients with Bartonella endocarditis should be treated in consultation with an infectious diseases specialist plus IV/IM in 3 equally divided doses 2 with or without doxycycline 200 mg/d IV/PO in 2 equally divided doses 6 (Continued) Baltimore et al Infective Endocarditis in Childhood: 2015 Update 1507 involve various prosthetic materials, including Gore-Tex, Dacron, or homografts, bacteriologic cure is often impossible without surgical intervention. Septic vegetations at these sites may lead to dehiscence, obstruction, or distal emboli.15,143 Extracardiac complications are the result of sepsis, immune complex mediated vasculitis, and, most importantly, embolic phenomena from septic vegetations. Embolic com- plications may involve the cerebral, pulmonary, renal, splenic, coronary, or peripheral arteries, depending on the original locus of infection. Neurological sequelae include stroke, brain abscess, hemorrhage, seizures, diffuse vasculitis, or menin- gitis, and these events may occur in up to 30% of cases.144 The incidence of stroke has been reported to be 6% in pediat- and 11% in those of all ages with CHD.146 Mycotic aneurysms may occur in any systemic artery or the pulmonary arteries but are particularly dangerous in the cere- bral circulation; surgical therapy may be used because of the risk of rupture. Numerous studies in adults102,147 have shown increased risk for embolization with vegetations >10 mm, which indicates a role for early surgical intervention in those with such large vegetations. Recently, this finding was sup- ported in a pediatric study.148 The location of the vegetation may also be a factor, with mitral valve anterior leaflet lesions having a higher rate of embolization than aortic valve vegeta- Particular organisms, namely, staphylococci, pneumococci, and fungi, also carry a high risk of embolism. Most emboli occur early in the course of the illness, but an increase in the size of the vegetation while a patient is receiving effective treatment may be predictive of The kidney and spleen may be involved during IE, with infarcts or abscesses related to emboli. The kidney may also be affected by glomerulonephritis secondary to immune complex depositions. Although mortality from IE has clearly improved in the current era, the mortality rate remains 5% to 10% for patients (including children) with this condition,24,146,151 with the risk of death clearly related to the presence of underly- ing heart disease, as shown in a review of a large pediatric In that study, the overall mortality was only 5%, but it was 48% in patients with tetralogy of Fallot and pulmonary atresia and 8% in patients who had pros- thetic valves. Recommendations 1. In general, for patients with IE, we recommend that the degree of illness not be considered a limitation to surgical intervention, because the alternative, to delay or defer surgery, can have dire consequences (Class I; Level of Evidence B). 2. Mycotic aneurysms may occur in any systemic artery or the pulmonary arteries but are particu- larly dangerous in the cerebral circulation; surgical therapy may be considered because of the risk of rupture (Class IIb; Level of Evidence B). Indications for Surgery Cardiovascular surgery is often urgently necessary and may be lifesaving in patients with IE, but decisions regarding surgical intervention are best made when individualized. Recommendations for surgical management of pediatric IE are mostly an extension of recommendations of experts for management of adult IE. The most common reasons for surgical management of IE are congestive heart failure, progressive valve dysfunction, and embolic phenomena. Prediction of an individual patient s risk for embolization Documented Bartonella, initially culture negative, determined to be positive by nonculture tests Doxycycline 200 mg/d IV or PO in 2 equally divided doses 6 IIa/B If gentamicin cannot be given, then replace it with rifampin 600 mg/d PO/IV in 2 equally divided doses plus IV/IM in 3 equally divided doses Pediatric dosage: Ceftriaxone 100 mg kg 1 IV/IM once daily; gentamicin 3 mg kg 1 IV/ IM in 3 equally divided doses; doxycycline 2 4 IV/PO in 2 equally divided doses; PO/IV in 2 equally divided doses As discussed in the text, these recommendations are based on consensus of experts and not experimental comparative studies (Class IIa; Level of Evidence C). Note: Pediatric dosage should not exceed that of a normal adult. IM indicates intramuscular; IV, intravenous; LOE, level of evidence; and PO, oral. *Dosages recommended are for patients with normal renal function. If ampicillin-sulbactam is unavailable, vancomycin is the suggested alternative (see Table 7 for empirical treatment of native valve infective endocarditis). See text and Table 7 for appropriate dosing of gentamicin. See Table 7 for appropriate dosing of vancomycin. Table 8. Continued Regimen Dosage and Route Duration, wk Strength of Recommendation (Class/LOE) Comments remains difficult, with conflicting data published regard- ing the specific value of echocardiographic determination of vegetation size or specific location as predictors.152,153 Nevertheless, left-sided heart lesions, specifically those involving the mitral valve anterior leaflet, particularly if associated with S aureus, appear to be at highest risk for However, at this time, there are no pediatric evidence-based data to indicate that prophylactic surgery to prevent a primary embolic event is definitively indicated given the immediate and long-term risks of valve replacement in childhood. Other important issues for which early surgery is used include perivalvular extension of infection, fungal endocar- ditis, persistent bacteremia despite appropriate antibiotic therapy, unstable prosthesis, ruptured sinus of Valsalva, or ventricular septal and mycotic aneurysms.156 158 The indica- tions for surgical intervention tabulated in Table 11 should be considered recommendations of experts.17 Although the clinical circumstances seem dire, even difficult aortic root complications can be treated successfully with aortic homografts or Ross procedure autografts.159,160 Depending on the degree of valve or great vessel root damage, valve- sparing operations are often possible.110,152,161 In some Late (>1 y) prosthetic valve placement Coagulase-negative staphylococci S aureus Viridans group streptococci Enterococcus species Fungi Corynebacterium species Dog-cat exposure Bartonella species Pasteurella species Capnocytophaga species Contact with contaminated milk or infected farm animals Brucella species Coxiella burnetii Erysipelothrix species Homelessness, body lice Bartonella species AIDS Salmonella species S pneumoniae S aureus Pneumonia, meningitis S pneumoniae Solid-organ transplant S aureus Aspergillus fumigatus Enterococcus species Candida species Gastrointestinal lesions Streptococcus bovis Enterococcus species Clostridium septicum HACEK indicates Haemophilus species, Aggregatibacter species, Cardiobacterium hominis, Eikenella corrodens, and Kingella species. Table 9. Continued Epidemiological Feature Common Microorganism(s) Table 9. Epidemiological Clues in Pathogenic Diagnosis of Culture-Negative Endocarditis Epidemiological Feature Common Microorganism(s) Injection drug use Staphylococcus aureus, including community-acquired methicillin/ oxacillin/nafcillin-resistant S aureus Coagulase-negative staphylococci -Hemolytic streptococci Fungi Aerobic Gram-negative bacilli, including Pseudomonas aeruginosa Polymicrobial Indwelling cardiovascular medical devices S aureus Coagulase-negative staphylococci Fungi Aerobic Gram-negative bacilli Corynebacterium spp Genitourinary disorders, infection, and manipulation, including pregnancy, delivery, and abortion Enterococcus species Group B streptococci (Streptococcus agalactiae) Listeria monocytogenes Aerobic Gram-negative bacilli Neisseria gonorrhoeae Chronic skin disorders, including recurrent infections S aureus -Hemolytic streptococci Poor dental health, dental procedures Viridans group streptococci Nutritionally variant streptococci Abiotrophia defectiva Granulicatella species Gemella species HACEK organisms Alcoholism, cirrhosis Bartonella species Aeromonas species Listeria species Streptococcus pneumoniae -Hemolytic streptococci Burn patients S aureus Aerobic Gram-negative bacilli, including P aeruginosa Fungi Diabetes mellitus S aureus -Hemolytic streptococci S pneumoniae Early ( 1 y) prosthetic valve placement Coagulase-negative staphylococci S aureus Aerobic Gram-negative bacilli Fungi Corynebacterium species Legionella species (Continued) Baltimore et al Infective Endocarditis in Childhood: 2015 Update 1509 circumstances, cardiological evaluation may suggest a need for early surgical therapy, performed even before steriliza- tion of blood. In a recent 15-year review of children treated for IE at the Texas Heart Institute in Houston, TX, early surgery was performed in 61% of patients, with most of these surgeries occurring within 7 days and half within 3 days of diagnosis.16 Several other studies have also shown that early surgery can be performed with low morbidity and mortality in childhood and improves the overall outcome Recent observational studies in adults have suggested that when adjusted for both selection and survi- vor biases, surgery in patients with left-sided IE, even when not considered urgent, may produce better outcomes and lower mortality than medical therapy alone.162,163 Although these data have not been replicated in specific pediatric- focused studies, the information does provide a reason- able framework for similar consideration in pediatric IE. Similarly, in prosthetic valve endocarditis, data from series in adults indicate that even aside from obvious indications for early surgery such as symptomatic heart failure, valve dehiscence, and great vessel root abscess formation, among others, surgery may benefit patients with relapsing pros- thetic valve endocarditis even if valvar function remains intact after prolonged medical therapy. Recommendations 1. Prophylactic surgery to prevent a primary embolic event is not recommended given the lack of proven benefit and long-term risks of valve replacement in childhood (Class III; Level of Evidence C). 2. Surgery may be considered for patients with relaps- ing prosthetic valve endocarditis even if valvar func- tion remains intact after prolonged medical therapy (Class IIb; Level of Evidence B). Prevention of Endocarditis For >5 decades, scientific organizations and public health- care policy groups around the world have advocated for the administration of antibiotic drugs for prophylaxis against IE. This recommendation, however, was never firmly grounded on well-designed, appropriately powered randomized clini- cal trials, and thus, scientific challenges to the concept emerged. These challenges were abetted by epidemio- logical facts that became apparent as well. Only 20% of endocarditis cases have actually been related to a preceding invasive procedure for which antibiotic drugs would have been recommended, and only 50% of cases of IE occur in people with an existing cardiac condition for which antibi- otic prophylaxis would have been prescribed. Thus, even the core epidemiology of IE was at variance with the existing, traditional guidelines. Moreover, increasing concern devel- oped in recent years that the dispensing of millions of doses of antibiotic drugs for a weakly supported rationale con- tributes to the development of antibiotic resistance. These issues were the impetus for extensive topical reviews per- formed by the AHA, the European Society of Cardiology, the British Society for Antimicrobial Chemotherapy, and other leading groups that all concluded that sharply limiting the use of antibiotic drugs for prophylaxis against IE was appropriate and timely. The 2007 AHA guideline on Prevention of Infective has become a widespread standard and is similar to the European Society of Cardiology statement. The British guidelines (NICE) carried the revisions furthest, with recommendations to eliminate prophylactic antibiotic drugs altogether for all patients under any circumstances. In sum- mary, the AHA and the European Society of Cardiology state- ments limit the use of prophylactic antibiotic drugs to patients in whom the risk for IE is highest (eg, patients with a history of previous IE), and equally important but somewhat more controversial, recommend antibiotic drugs be considered for those patients with the greatest risk for morbidity or mortality from IE (eg, heart transplant patients with a valvulopathy in the implanted heart). Since the publications of these recommendations, at least 1 study has documented the lack of any demonstrable increase in IE as a cause of hospitalization for children,72 and another has carefully documented the absence of any impact on the rate of IE case development in the United Kingdom, where the NICE guidelines have been in place and where antibiotic dispensing for IE prophylaxis is moni- Children who are at risk for IE and their families and care providers can benefit from education about the impor- tance of good oral health and the techniques useful for its maintenance. Additionally, children with cyanosis may have specific periodontal concerns, which makes optimum oral hygiene particularly important for them.3 The AHA recom- mends that for those in the highest-risk groups, there may still be a role for prophylactic antibiotic drugs. Families of children and young adults, in particular, are counseled that their risk for IE might actually increase as they become subject to cardiovascular therapies for their CHD, although those conditions might not have required IE prophylaxis before treatment. In this regard, valve replacement and septal defect occlusion with prosthetic devices are relevant exam- ples. In the last review of IE prophylaxis, the conditions the Table 10. Clinical Situations Constituting High Risk for Complications of IE Prosthetic cardiac valves Left-sided IE Staphylococcus aureus IE Fungal IE Previous IE Prolonged clinical symptoms (>3 mo) Cyanotic congenital heart disease Patients with systemic-to-pulmonary shunts Poor clinical response to antimicrobial therapy IE indicates infective endocarditis. Reprinted from Bayer et al.102 Copyright 1998, American Heart Association, Inc. AHA recommended as highest risk for adverse outcomes from IE and for which prophylaxis before high-risk dental procedures is reasonable included cardiac valve repair with a prosthetic valve or prosthetic material; previous IE; cer- tain CHD (unrepaired cyanotic CHD, repaired CHD with prosthetic material or device during the first 6 months after the procedure, repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device); and recipients of cardiac transplants who develop Finally, as growing numbers of children successfully tran- sition to adult-based healthcare circumstances, carrying their complex cardiovascular histories with them, the issues sur- rounding IE prevention will continually be reiterated as part of their healthcare maintenance program. Recommendation 1. Children with cyanosis may have specific periodon- tal concerns, which makes optimum oral hygiene particularly important for them. The AHA recom- mends that for those in the highest-risk groups, prophylactic antibiotic drugs before certain dental procedures may be considered3 (Class IIb; Level of Evidence C). Table 11. Echocardiographic Features Suggesting Potential Need for Surgical Intervention* Vegetation Persistent vegetation after systemic embolization Anterior mitral leaflet vegetation, particularly with size >10 mm 1 Embolic event during first 2 wk of antimicrobial therapy 2 Embolic events during or after antimicrobial therapy Increase in vegetation size after 4 wk of antimicrobial therapy Valvular dysfunction Acute aortic or mitral insufficiency with signs of ventricular failure Heart failure unresponsive to medical therapy Valve perforation or rupture Perivalvular extension Valvular dehiscence, rupture, or fistula New heart block Large abscess or extension of abscess despite appropriate antimicrobial therapy *See text for more complete discussion or indications for surgery based on vegetation characterizations. Surgery may be required because of risk of recurrent embolization. Surgery may be required because of risk of embolization. Surgery may be required because of heart failure or failure of medical therapy. Reprinted from Bayer et al.102 Copyright 1998, American Heart Association, Inc. Writing Group Disclosures Writing Group Member Employment Research Grant Other Research Support Speakers Bureau/Honoraria Expert Witness Ownership Interest Consultant/ Advisory Board Other Robert S. Baltimore Yale University School of Medicine None None None None None None None Michael Gewitz New York Medical College None None None None None None None Larry M. Baddour Mayo Clinic None None None None None None None Lee B. Beerman Children s Hospital of Pittsburgh of UPMC None None None None None None None Mary Anne Jackson Children s Mercy Hospitals NVSN ; VTEU None None None None AAP*; University Invited Professor* None Peter B. Lockhart Carolinas Medical Center None None None None None None None Elfriede Pahl Robert Lurie Children s Hospital Chicago None None None None None None None Gordon E. Schutze Baylor College of Medicine/Texas Children s Hospital None None None None None None None Stanford T. Shulman Lurie Children s Hospital/ Northwestern University Medical School None None None None None None None Rodney Willoughby, Jr Children s Hospital of Wisconsin None None None None None None None This table represents the relationships of writing group members that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all members of the writing group are required to complete and submit. A relationship is considered to be significant if (a) the person receives $10000 or more during any 12-month period, or 5% or more of the person s gross income; or (b) the person owns 5% or more of the voting stock or share of the entity, or owns $10000 or more of the fair market value of the entity. A relationship is considered to be modest if it is less than significant under the preceding definition. *Modest. Significant. Disclosures Baltimore et al Infective Endocarditis in Childhood: 2015 Update 1511 References 1. Ferrieri P, Gewitz MH, Gerber MA, Newburger JW, Dajani AS, Shulman ST, Wilson W, Bolger AF, Bayer A, Levison ME, Pallasch TJ, Gage TW, Taubert KA; Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the American Heart Association Council on Cardiovascular Disease in the Young. Unique features of infective endocarditis in child- hood. Circulation. 2002;105:2115 2126. 2. Baddour LM, Wilson WR, BayerAS, FowlerVG, BolgerAF, Levison ME., Ferrieri P, Gerber MA, Tani LY, Gewitz MH, Tong DC, Steckelberg JM, Baltimore RS, Shulman ST, Burns JC, Falace DA, Newburger JW, Pallasch TJ, Takahashi M. Taubert KA. Infective endocarditis: diagnosis, antimi- crobial therapy, and management of complications: a statement for health- care professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: executive summary [published correction appears in Circulation. 2005;112:2374]. Circulation 2005;111:3167 3184. doi: 10.1161/CIRCULATIONAHA.105.165563. 3. Wilson W, Taubert KA, Gewitz M, Lockhart PB, Baddour LM, Levison M, Bolger A, Cabell CH, Takahashi M, Baltimore RS, Newburger JW, Strom BL, Tani LY, Gerber M, Bonow RO, Pallasch T, Shulman ST, Rowley AH, Burns JC, Ferrieri P, Gardner T, Goff D, Durack DT. Prevention of infective endocarditis: guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group [published correction appears in Circulation. 2007;116:e376-377]. Circulation. 2007;116:1736 1754. doi: 10.1161/CIRCULATIONAHA.106.183095. 4. Van Hare GF, Ben-Shachar G, Liebman J, Boxerbaum B, Riemenschneider TA. Infective endocarditis in infants and children during the past 10 years: a decade of change. Am Heart J. 1984;107:1235 1240. 5. Pasquali SK, He X, Mohamad Z, McCrindle BW, Newburger JW, Li JS, Shah SS. Trends in endocarditis hospitalizations at US children s hospi- tals: impact of the 2007 American Heart Association antibiotic prophy- laxis guidelines. Am Heart J 2012;143:894 899. 6. Baltimore RS. Infective endocarditis. In: Jenson HB, Baltimore RS, eds. Pediatric Infectious Diseases: Principles and Practice. 2nd ed. Philadelphia, PA: Saunders; 2002. 7. Rushani D, Kaufman JS, Ionescu-Ittu R, Mackie AS, Pilote L, Therrien J, Marelli AJ. Infective endocarditis in children with congenital heart dis- ease: cumulative incidence and predictors. Circulation. 2013;128:1412 1419. doi: 10.1161/CIRCULATIONAHA.113.001827. 8. Rosenthal LB, Feja KN, Levasseur SM, Alba LR, Gersony W, Saiman L. The changing epidemiology of pediatric endocarditis at a children s hos- pital over seven decades. Pediatr Cardiol. 2010;31:813 820. doi: 10.1007/ s00246-010-9709-6. 9. Stull TL, LiPuma JJ. Endocarditis in children. In: Kaye D, ed. Infective Endocarditis. 2nd ed. New York, NY: Raven Press; 1992:313 327. 10. Saiman L, Prince A, Gersony WM. Pediatric infective endocarditis in the modern era. J Pediatr. 1993;122:847 853. 11. Martin JM, Neches WH, Wald ER. Infective endocarditis: 35 years of experience at a children s hospital. Clin Infect Dis. 1997;24:669 675. 12. Morris CD, Reller MD, Menashe VD. Thirty-year incidence of infec- tive endocarditis after surgery for congenital heart defect. JAMA. 1998;279:599 603. 13. Stockheim JA, Chadwick EG, Kessler S, Amer M, Abdel-Haq N, Dajani AS, Shulman ST. Are the Duke criteria superior to the Beth Israel criteria for the diagnosis of infective endocarditis in children? Clin Infect Dis. 1998;27:1451 1456. 14. Hoyer A, Silberbach M. Infective endocarditis. Pediatr Rev. 2005;26:394 400. 15. Mahar T, Katzman P, Alfieris G. A case of fatal septic pulmonary embolus arising from an infected Sano conduit. Pediatr Cardiol. 2009;30:181 183. doi: 10.1007/s00246-008-9276-2. 16. Shamszad P, Khan MS, Rossano JW, Fraser CD Jr. Early surgical ther- apy of infective endocarditis in children: a 15-year experience. J Thorac Cardiovasc Surg. 2013;146:506 511. doi: 10.1016/j.jtcvs.2012.12.001. 17. Murakami T, Niwa K,Yoshinaga M, Nakazawa M. Factors associated with surgery for active endocarditis in congenital heart disease. Int J Cardiol. 2012;157:59 62. doi: 10.1016/j.ijcard.2010.11.016. 18. Russell HM, Johnson SL, Wurlitzer KC, Backer CL. Outcomes of sur- gical therapy for infective endocarditis in a pediatric population: a 21-year review. Ann Thorac Surg. 2013;96:171 174. doi: 10.1016/ j.athoracsur.2013.02.031. 19. Kutty S, Hazeem AA, Brown K, Danford CJ, Worley SE, Delaney JW, Danford DA, Latson LA. Long-term (5- to 20-year) outcomes after trans- catheter or surgical treatment of hemodynamically significant isolated secundum atrial septal defect. Am J Cardiol. 2012;109:1348 1352. doi: 10.1016/j.amjcard.2011.12.031. 20. Kassis I, Shachor-Meyouhas Y, Khatib I, Khoury A, Le TP, Lorber A. Kingella endocarditis after closure of ventricular septal defect with a transcatheter device. Pediatr Infect Dis J. 2012;31:105 106. doi: 10.1097/ INF.0b013e31823c3ec1. 21. Scheuerman O, Bruckheimer E, Marcus N, Hoffer V, Garty BZ. Endocarditis after closure of ventricular septal defect by transcatheter device. Pediatrics. 2006;117:e1256 e1258. doi: 10.1542/peds.2005-2498. 22. Slesnick TC, Nugent AW, Fraser CD Jr, Cannon BC. Images in cardio- vascular medicine: incomplete endothelialization and late development of acute bacterial endocarditis after implantation of an Amplatzer sep- tal occluder device. Circulation. 2008;117:e326 e327. doi: 10.1161/ CIRCULATIONAHA.107.754069. 23. Saint-Andr C, Iriart X, Ntsinjana H, Thambo JB. Residual shunt after ductus arteriosusoccluderimplantationcomplicatedbylateendocarditis.Circulation. 2012;125:840 842. doi: 10.1161/CIRCULATIONAHA.111.024521. 24. Day MD, Gauvreau K, Shulman S, Newburger JW. Characteristics of children hospitalized with infective endocarditis [published correction appears in Circulation. 2010;122:e560]. Circulation. 2009;119:865 870. doi: 10.1161/CIRCULATIONAHA.108.798751. 25. Opie GF, Fraser SH, Drew JH, Drew S. Bacterial endocarditis in neonatal intensive care. J Paediatr Child Health. 1999;35:545 548. 26. Oelberg DG. Neonatal endocarditis: neither rare nor fatal. Clin Pediatr (Phila). 1998;37:747 748. 27. Millard DD, Shulman ST. The changing spectrum of neonatal endocardi- tis. Clin Perinatol. 1988;15:587 608. 28. Oelberg DG, Fisher DJ, Gross DM, Denson SE, Adcock EW 3rd. Endocarditis in high-risk neonates. Pediatrics. 1983;71:392 397. 29. Symchych PS, Krauss AN, Winchester P. Endocarditis following intra- cardiac placement of umbilical venous catheters in neonates. J Pediatr. 1977;90:287 289. 30. Danne C, Entenza JM, Mallet A, Briandet R, D barbouill M, Nato F, Glaser P, Jouvion G, Moreillon P, Trieu-Cuot P, Dramsi S. Molecular characterization of a Streptococcus gallolyticus genomic island encoding a pilus involved in endocarditis. J Infect Dis. 2011;204:1960 1970. doi: 10.1093/infdis/jir666. 31. QueYA, Moreillon P. Infective endocarditis. Nat Rev Cardiol. 2011;8:322 336. doi: 10.1038/nrcardio.2011.43. 32. Patti JM, Allen BL, McGavin MJ, H k M. MSCRAMM-mediated adherence of microorganisms to host tissues. Annu Rev Microbiol. 1994;48:585 617. doi: 10.1146/annurev.mi.48.100194.003101. 33. Kitten T, Munro CL, Wang A, Macrina FL. Vaccination with FimA from Streptococcus parasanguis protects rats from endocarditis caused by other viridans streptococci. Infect Immun. 2002;70:422 425. Reviewer Disclosures Reviewer Employment Research Grant Other Research Support Speakers Bureau/Honoraria Expert Witness Ownership Interest Consultant/ Advisory Board Other Robert Campbell Sibley Heart Center Cardiology None None None None None None None Jeffrey Starke Baylor College of Medicine None None None None None None None This table represents the relationships of reviewers that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all reviewers are required to complete and submit. A relationship is considered to be significant if (a) the person receives $10000 or more during any 12-month period, or 5% or more of the person s gross income; or (b) the person owns 5% or more of the voting stock or share of the entity, or owns $10000 or more of the fair market value of the entity. A relationship is considered to be modest if it is less than significant under the preceding definition. 34. Donlan RM. Biofilm formation: a clinically relevant microbiological pro- cess. Clin Infect Dis. 2001;33:1387 1392. doi: 10.1086/322972. 35. Papaioannou W, Gizani S, Haffajee AD, Quirynen M, Mamai-Homata E, Papagiannoulis L. The microbiota on different oral surfaces in healthy children. Oral Microbiol Immunol. 2009;24:183 189. doi: 10.1111/j.1399-302X.2008.00493.x. 36. Rozkiewicz D, Daniluk T, Zaremba ML, Cylwik-Rokicka D, Luczaj- Cepowicz E, Milewska R, Marczuk-Kolada G, Stokowska W. Bacterial composition in the supragingival plaques of children with and without dental caries. Adv Med Sci. 2006;51(suppl 1):182 186. 37. K n nen E. Development of oral bacterial flora in young children. Ann Med. 2000;32:107 112. 38. K n nen E. Oral colonization by anaerobic bacteria during childhood: role in health and disease. Oral Dis. 1999;5:278 285. 39. Ooshima T, Nishiyama N, Hou B, Tamura K, Amano A, Kusumoto A, Kimura S. Occurrence of periodontal bacteria in healthy children: a 2-year longitudinal study. Community Dent Oral Epidemiol. 2003;31:417 425. 40. Hess J, Holloway Y, Dankert J. Incidence of postextraction bactere- mia under penicillin cover in children with cardiac disease. Pediatrics. 1983;71:554 558. 41. Peterson LJ, Peacock R. The incidence of bacteremia in pediatric patients following tooth extraction. Circulation. 1976;53:676 679. 42. Roberts GJ, Holzel HS, Sury MR, Simmons NA, Gardner P, Longhurst P. Dental bacteremia in children. Pediatr Cardiol. 1997;18:24 27. doi: 10.1007/s002469900103. 43. Roberts GJ. Dentists are innocent! Everyday bacteremia is the real cul- prit: a review and assessment of the evidence that dental surgical proce- dures are a principal cause of bacterial endocarditis in children. Pediatr Cardiol. 1999;20:317 325. doi: 10.1007/s002469900477. 44. Roberts GJ, Watts R, Longhurst P, Gardner P. Bacteremia of dental origin and antimicrobial sensitivity following oral surgical procedures in chil- dren. Pediatr Dent. 1998;20:28 36. 45. Lockhart PB, Brennan MT, Kent ML, Norton HJ, Weinrib DA. Impact of amoxicillin prophylaxis on the incidence, nature, and duration of bac- teremia in children after intubation and dental procedures. Circulation. 2004;109:2878 2884. doi: 10.1161/01.CIR.0000129303.90488.29. 46. Sonbol H, Spratt D, Roberts GJ, Lucas VS. Prevalence, intensity and identity of bacteraemia following conservative dental procedures in children. Oral Microbiol Immunol. 2009;24:177 182. doi: 10.1111/ j.1399-302X.2008.00492.x. 47. Lucas VS, Gafan G, Dewhurst S, Roberts GJ. Prevalence, intensity and nature of bacteraemia after toothbrushing. J Dent. 2008;36:481 487. doi: 10.1016/j.jdent.2008.03.005. 48. Tom s I,Alvarez M, Limeres J, Tom s M, Medina J, Otero JL, Diz P. Effect of a chlorhexidine mouthwash on the risk of postextraction bacteremia. Infect Control Hosp Epidemiol. 2007;28:577 582. doi: 10.1086/516663. 49. Coulter WA, Coffey A, Saunders ID, Emmerson AM. Bacteremia in chil- dren following dental extraction. J Dent Res. 1990;69:1691 1695. 50. Berry FA Jr, Yarbrough S, Yarbrough N, Russell CM, Carpenter MA, Hendley JO. Transient bacteremia during dental manipulation in children. Pediatrics. 1973;51:476 479. 51. Roberts GJ, Gardner P, Longhurst P, Black AE, Lucas VS. Intensity of bacteraemia associated with conservative dental procedures in children. Br Dent J. 2000;188:95 98. 52. Lucas VS, Omar J, Vieira A, Roberts GJ. The relationship between odon- togenic bacteraemia and orthodontic treatment procedures. Eur J Orthod. 2002;24:293 301. 53. On a O, Aydemir S, Ersin N, Koca H. Bacteremia incidence in pediatric patients under dental general anesthesia. Congenit Heart Dis. 2006;1:224 228. doi: 10.1111/j.1747-0803.2006.00039.x. 54. Brennan MT, Kent ML, Fox PC, Norton HJ, Lockhart PB. The impact of oral disease and nonsurgical treatment on bacteremia in children. J Am Dent Assoc. 2007;138:80 85. 55. Bhanji S, Williams B, Sheller B, Elwood T, Mancl L. Transient bacteremia induced by toothbrushing: a comparison of the Sonicare toothbrush with a conventional toothbrush. Pediatr Dent. 2002;24:295 299. 56. Roberts GJ, Jaffray EC, Spratt DA, Petrie A, Greville C, Wilson M, Lucas VS. Duration, prevalence and intensity of bacteraemia after den- tal extractions in children. Heart. 2006;92:1274 1277. doi: 10.1136/ hrt.2004.046581. 57. Lucas VS, Lytra V, Hassan T, Tatham H, Wilson M, Roberts GJ. Comparison of lysis filtration and an automated blood culture system (BACTEC) for detection, quantification, and identification of odontogenic bacteremia in children. J Clin Microbiol. 2002;40:3416 3420. 58. Faigel HC, Gaskill WF. Bacteremia in pediatric patients following dental manipulations. Clin Pediatr (Phila). 1975;14:562 565. 59. Hess J, HollowayY, Dankert J. Penicillin prophylaxis in children with car- diac disease: postextraction bacteremia and penicillin-resistant strains of viridans streptococci. J Infect Dis. 1983;147:133 136. 60. Speck WT, Spear SS, Krongrad E, Mandel L, Gersony WM. Transient bacteremia in pediatric patients after dental extraction. Am J Dis Child. 1976;130:406 407. 61. De Leo AA, Schoenknecht FD, Anderson MW, Peterson JC. The inci- dence of bacteremia following oral prophylaxis on pediatric patients. Oral Surg Oral Med Oral Pathol. 1974;37:36 45. 62. Hurwitz GA, Speck WT, Keller GB. Absence of bacteremia in children after prophylaxis. Oral Surg Oral Med Oral Pathol. 1971;32:891 894. 63. Speck WT, Hurwitz GA, Keller GB. Transient bacteremia in pediatric patientsfollowingdentalmanipulation.AmJDisChild.1971;121:286 288. 64. Roberts GJ, Simmons NB, Longhurst P, Hewitt PB. Bacteraemia follow- ing local anaesthetic injections in children. Br Dent J. 1998;185:295 298. 65. Roberts GJ, Radford P, Holt R. Prophylaxis of dental bacteraemia with oral amoxycillin in children. Br Dent J. 1987;162:179 182. 66. Lockhart PB, Brennan MT, Thornhill M, Michalowicz BS, Noll J, Bahrani- Mougeot FK, Sasser HC. Poor oral hygiene as a risk factor for infective endocarditis-related bacteremia. J Am Dent Assoc. 2009;140:1238 1244. 67. Dajani AS, Bisno AL, Chung KJ, Durack DT, Freed M, Gerber MA, Karchmer AW, Millard HD, Rahimtoola S, Shulman ST, Watanakunakorn C, Taubert KA. Prevention of bacterial endocarditis: recommendations by the American Heart Association. JAMA. 1990;264:2919 2922. 68. Lockhart PB, Brennan MT, Sasser HC, Fox PC, Paster BJ, Bahrani- Mougeot FK. Bacteremia associated with toothbrushing and den- tal extraction. Circulation. 2008;117:3118 3125. doi: 10.1161/ CIRCULATIONAHA.107.758524. 69. Dajani AS, Taubert KA, Wilson W, Bolger AF, Bayer A, Ferrieri P, Gewitz MH, Shulman ST, Nouri S, Newburger JW, Hutto C, Pallasch TJ, Gage TW, Levison ME, Peter G, Zuccaro G Jr. Prevention of bacterial endocar- ditis: recommendations by the American Heart Association. Circulation. 1997;96:358 366. doi: 10.1161/01.CIR.96.1.358. 70. Forner L, Larsen T, Kilian M, Holmstrup P. Incidence of bacteremia after chewing, tooth brushing and scaling in individuals with peri- odontal inflammation. J Clin Periodontol. 2006;33:401 407. doi: 10.1111/j.1600-051X.2006.00924.x. 71. National Institute for Health and Clinical Excellence. Prophylaxis against infective endocarditis: antimicrobial prophylaxis against infective endo- carditis in adults and children undergoing interventional procedures. 2008. http://www.nice.org.uk/CG064. Accessed September 4, 2015. 72. Thornhill MH, Dayer MJ, Forde JM, Corey GR, Chu VH, Couper DJ, Lockhart PB. Impact of the NICE guideline recommending cessation of antibiotic prophylaxis for prevention of infective endocarditis: before and after study. BMJ. 2011;342:d2392. 73. Dayer MJ, Pasquali SK, Cohen-Wolkowiez M, Thornhill MH, Couper D, Forde JM, Lockhart PB, Li JS. The impact of cessation of antibiotic pro- phylaxis in children: a population study in England. Circulation. 2011; 124:A12225. 74. Durack DT, Lukes AS, Bright DK. New criteria for diagnosis of infec- tive endocarditis: utilization of specific echocardiographic findings: Duke Endocarditis Service. Am J Med. 1994;96:200 209. 75. Li JS, Sexton DJ, Mick N, Nettles R, Fowler VG Jr, Ryan T, Bashore T, Corey GR. Proposed modifications to the Duke criteria for the diag- nosis of infective endocarditis. Clin Infect Dis. 2000;30:633 638. doi: 10.1086/313753. 76. Bendig EA, Singh J, Butler TJ, Arrieta AC. The impact of the central venous catheter on the diagnosis of infectious endocarditis using Duke criteria in children with Staphylococcus aureus bacteremia. Pediatr Infect Dis J. 2008;27:636 639. doi: 10.1097/INF.0b013e31816b78c8. 77. Del Pont JM, De Cicco LT, Vartalitis C, Ithurralde M, Gallo JP, Vargas F, Gianantonio CA, Quir s RE. Infective endocarditis in children: clinical analyses and evaluation of two diagnostic criteria. Pediatr Infect Dis J. 1995;14:1079 1086. 78. Tissi res P, Gervaix A, Beghetti M, Jaeggi ET. Value and limitations of the von Reyn, Duke, and modified Duke criteria for the diagnosis of infective endocarditis in children. Pediatrics. 2003;112(pt 1):e467. 79. Wei HH, Wu KG, Sy LB, Chen CJ, Tang RB. Infectious endocarditis in pedi- atric patients: analysis of 19 cases presenting at a medical center. J Microbiol Immunol Infect. 2010;43:430 437. doi: 10.1016/S1684-1182(10)60066-7. 80. Syed FF, Millar BC, Prendergast BD. Molecular technology in context: a current review of diagnosis and management of infective endocarditis. Prog Cardiovasc Dis. 2007;50:181 197. doi: 10.1016/j.pcad.2007.08.002. Baltimore et al Infective Endocarditis in Childhood: 2015 Update 1513 81. Johnson DH, Rosenthal A, Nadas AS. A forty-year review of bacterial endocarditis in infancy and childhood. Circulation. 1975;51:581 588. 82. M ller HP, Heinecke A, Borneff M, Kiencke C, Knopf A, Pohl S. Eradication of Actinobacillus actinomycetemcomitans from the oral cav- ity in adult periodontitis. J Periodontal Res. 1998;33:49 58. 83. Slots J, Reynolds HS, Genco RJ. Actinobacillus actinomycetemcomitans in human periodontal disease: a cross-sectional microbiological investiga- tion. Infect Immun. 1980;29:1013 1020. 84. Weber R, Berger C, Balmer C, Kretschmar O, Bauersfeld U, Pretre R, Nadal D, Knirsch W. Interventions using foreign material to treat congenital heart disease in children increase the risk for infective endocarditis. Pediatr Infect Dis J. 2008;27:544 550. doi: 10.1097/INF.0b013e3181690374. 85. Alshammary A, Hervas-Malo M, Robinson JL. Pediatric infective endo- carditis: has Staphylococcus aureus overtaken viridans group streptococci as the predominant etiological agent? Can J Infect Dis Med Microbiol. 2008;19:63 68. 86. Tunkel AR, Kaye D. Endocarditis with negative blood cultures. N Engl J Med. 1992;326:1215 1217. doi: 10.1056/NEJM199204303261809. 87. Brouqui P, Raoult D. New insight into the diagnosis of fastidious bac- terial endocarditis. FEMS Immunol Med Microbiol. 2006;47:1 13. doi: 10.1111/j.1574-695X.2006.00054.x. 88. Bosshard PP, Kronenberg A, Zbinden R, Ruef C, B ttger EC, Altwegg M. Etiologic diagnosis of infective endocarditis by broad-range polymerase chain reaction: a 3-year experience. Clin Infect Dis. 2003;37:167 172. doi: 10.1086/375592. 89. Fournier PE, Thuny F, Richet H, Lepidi H, Casalta JP, Arzouni JP, Maurin M, C lard M, Mainardi JL, Caus T, Collart F, Habib G, Raoult D. Comprehensive diagnostic strategy for blood culture-negative endocardi- tis: a prospective study of 819 new cases. Clin Infect Dis. 2010;51:131 140. doi: 10.1086/653675. 90. Casalta JP, Gouriet F, Roux V, Thuny F, Habib G, Raoult D. Evaluation of the LightCycler SeptiFast test in the rapid etiologic diagnostic of infec- tious endocarditis. Eur J Clin Microbiol Infect Dis. 2009;28:569 573. doi: 10.1007/s10096-008-0672-6. 91. Vondracek M, Sartipy U, Aufwerber E, Julander I, Lindblom D, Westling K. 16S rDNA sequencing of valve tissue improves microbiological diag- nosis in surgically treated patients with infective endocarditis. J Infect. 2011;62:472 478. doi: 10.1016/j.jinf.2011.04.010. 92. Mar n M, Mu oz P, S nchez M, del Rosal M, Alcal L, Rodr guez- Cr ixems M, Bouza E; Group for the Management of Infective Endocarditis of the Gregorio Mara n Hospital. Molecular diagnosis of infective endocarditis by real-time broad-range polymerase chain reac- tion (PCR) and sequencing directly from heart valve tissue. Medicine (Baltimore). 2007;86:195 202. doi: 10.1097/MD.0b013e31811f44ec. 93. Gauduchon V, Chalabreysse L, Etienne J, C lard M, Benito Y, Lepidi H, Thivolet-B jui F, Vandenesch F. Molecular diagnosis of infective endo- carditis by PCR amplification and direct sequencing of DNA from valve tissue. J Clin Microbiol. 2003;41:763 766. 94. Wolff TY, Moser C, Bundgaard H, H iby N, Nielsen PH, Thomsen TR. Detection of microbial diversity in endocarditis using cultivation-inde- pendent molecular techniques. Scand J Infect Dis. 2011;43:857 869. doi: 10.3109/00365548.2011.598877. 95. Lang S, Watkin RW, Lambert PA, Littler WA, Elliott TS. Detection of bacterial DNA in cardiac vegetations by PCR after the completion of anti- microbial treatment for endocarditis. Clin Microbiol Infect. 2004;10:579 581. doi: 10.1111/j.1198-743X.2004.00821.x. 96. Sukocheva OA, Marmion BP, Storm PA, Lockhart M, Turra M, Graves S. Long-term persistence after acute Q fever of non-infective Coxiella bur- netii cell components, including antigens. QJM. 2010;103:847 863. doi: 10.1093/qjmed/hcq113. 97. Voldstedlund M, N rum Pedersen L, Baandrup U, Klaaborg KE, Fuursted K. Broad-range PCR and sequencing in routine diag- nosis of infective endocarditis. APMIS. 2008;116:190 198. doi: 10.1111/j.1600-0463.2008.00942.x. 98. Barbour SI, Louie EK, O Keefe JP. Penetration of the atrialventricular septum by spread of infection from aortic valve endocarditis: early diag- nosis by transesophageal echocardiography and implications for surgical management. Am Heart J. 1996;132:1287 1289. 99. Narducci ML, Pelargonio G, Russo E, Marinaccio L, Di Monaco A, Perna F, Bencardino G, Casella M, Di Biase L, Santangeli P, Palmieri R, Lauria C, Al Mohani G, Di Clemente F, Tondo C, Pennestri F, Ierardi C, Rebuzzi AG, Crea F, Bellocci F, Natale A, Dello Russo A. Usefulness of intra- cardiac echocardiography for the diagnosis of cardiovascular implantable electronic device-related endocarditis. J Am Coll Cardiol. 2013;61:1398 1405. doi: 10.1016/j.jacc.2012.12.041. 100. Koneru JN, Ellenbogen KA. Detection of transvenous pacemaker and ICD lead vegetations: the ICE cold facts. J Am Coll Cardiol. 2013;61:1406 1408. doi: 10.1016/j.jacc.2013.01.016. 101. Prakash S, Bredikis A. Pacemaker endocarditis viewed via intracardiac ultrasonography. Tex Heart Inst J. 2008;35:487 488. 102. Bayer AS, Bolger AF, Taubert KA, Wilson W, Steckelberg J, Karchmer AW, Levison M, Chambers HF, Dajani AS, Gewitz MH, Newburger JW, Gerber MA, Shulman ST, Pallasch TJ, Gage TW, Ferrieri P. Diagnosis and management of infective endocarditis and its complications. Circulation. 1998;98:2936 2948. 103. Kini V, Logani S, Ky B, Chirinos JA, Ferrari VA, St John Sutton MG, Wiegers SE, Kirkpatrick JN. Transthoracic and transesophageal echo- cardiography for the indication of suspected infective endocarditis: vegetations, blood cultures and imaging. J Am Soc Echocardiogr. 2010;23:396 402. doi: 10.1016/j.echo.2009.12.017. 104. Penk JS, Webb CL, Shulman ST, Anderson EJ. Echocardiography in pe- diatric infective endocarditis. Pediatr Infect Dis J. 2011;30:1109 1111. doi: 10.1097/INF.0b013e31822d320b. 105. Durack DT, Beeson PB. Experimental bacterial endocarditis, I: coloniza- tion of a sterile vegetation. Br J Exp Pathol. 1972;53:44 49. 106. Durack DT, Beeson PB. Experimental bacterial endocarditis, II: survival of a bacteria in endocardial vegetations. Br J Exp Pathol. 1972;53:50 53. 107. Valente AM, Jain R, Scheurer M, Fowler VG Jr, Corey GR, Bengur AR, Sanders S, Li JS. Frequency of infective endocarditis among in- fants and children with Staphylococcus aureus bacteremia. Pediatrics. 2005;115:e15 e19. doi: 10.1542/peds.2004-1152. 108. Santoro J, Ingerman M. Response to therapy: relapses and reinfections. In: Kaye D, ed. Infective Endocarditis. 2nd ed. New York, NY: Raven Press; 1992:423 434. 109. Baddour LM, Wilson WR, Bayer AS, Fowler VG Jr, Tleyjeh IM, Rybak MJ, Barsic B, Lockhart PB, Gewitz MH, Levison ME, Bolger AF, Steckelberg JM, Baltimore RS, Fink AM, O Gara P, Taubert KA; on behalf of the American Heart Association Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young, Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and Stroke Council. Infective endocarditis in adults: diagnosis, antimicrobial therapy, and management of complications: a scientific statement for healthcare professionals from the American Heart Association [published on- line ahead of print September 14, 2015]. Circulation. doi: 10.1161/ CIR.0000000000000296. 110. Hickey EJ, Jung G, Manlhiot C, Sakopoulos AG, Caldarone CA, Coles JG, Van Arsdell GS, McCrindle BW. Infective endocarditis in children: native valve preservation is frequently possible despite advanced clini- cal disease. Eur J Cardiothorac Surg. 2009;35:130 135. doi: 10.1016/j. ejcts.2008.08.020. 111. Le Guillou S, Casalta JP, Fraisse A, Kreitmann B, Chabrol B, Dubus JC, Bosdure E. Infective endocarditis in children without underlying heart disease: a retrospective study analyzing 11 cases [in French]. Arch Pediatr. 2010;17:1047 1055. doi: 10.1016/j.arcped.2010.03.019. 112. KarchmerAW, Moellering RC Jr, Maki DG, Swartz MN. Single-antibiotic therapy for streptococcal endocarditis. JAMA. 1979;241:1801 1806. 113. Francioli P, Etienne J, Hoign R, Thys JP, Gerber A. Treatment of streptococcal endocarditis with a single daily dose of ceftriaxone so- dium for 4 weeks: efficacy and outpatient treatment feasibility. JAMA. 1992;267:264 267. 114. Wilson WR, Thompson RL, Wilkowske CJ, Washington JA 2nd, Giuliani ER, Geraci JE. Short-term therapy for streptococcal infective endocardi- tis: combined intramuscular administration of penicillin and streptomy- cin. JAMA. 1981;245:360 363. 115. Sexton DJ, Tenenbaum MJ, Wilson WR, Steckelberg JM, Tice AD, Gilbert D, Dismukes W, Drew RH, Durack DT. Ceftriaxone once daily for four weeks compared with ceftriaxone plus gentamicin once daily for two weeks for treatment of endocarditis due to penicillin-susceptible streptococci: Endocarditis Treatment Consortium Group. Clin Infect Dis. 1998;27:1470 1474. 116. Lindberg J, Prag J, Sch nheyder HC. Pneumococcal endocarditis is not just a disease of the past: an analysis of 16 cases diagnosed in Denmark 1986-1997. Scand J Infect Dis. 1998;30:469 472. 117. Aronin SI, Mukherjee SK, West JC, Cooney EL. Review of pneumo- coccal endocarditis in adults in the penicillin era. Clin Infect Dis. 1998;26:165 171. 118. LefortA, Mainardi JL, Selton-Suty C, Casassus P, Guillevin L, Lortholary O; the Pneumococcal Endocarditis Study Group. Streptococcus pneumoniae endocarditis in adults: a multicenter study in France in the era of penicillin resistance (1991 1998). Medicine (Baltimore). 2000; 79: 327 337. 119. Givner LB, Mason EO Jr, Tan TQ, Barson WJ, Schutze GE, Wald ER, Bradley JS, Hoffman J,Yogev R, Kaplan SL. Pneumococcal endocarditis in children. Clin Infect Dis. 2004;38:1273 1278. doi: 10.1086/383323. 120. Eliopoulos GM. Enterococcal endocarditis. In: Kaye D, ed. Infective Endocarditis. 2nd ed. New York, NY: Raven Press; 1992:209 224. 121. Eliopoulos GM. Aminoglycoside resistant enterococcal endocarditis. Infect Dis Clin North Am. 1993;7:117 133. 122. Wilson WR, Karchmer AW, Dajani AS, Taubert KA, Bayer A, Kaye D, Bisno AL, Ferrieri P, Shulman ST, Durack DT. Antibiotic treatment of adults with infective endocarditis due to streptococci, enterococci, staph- ylococci, and HACEK microorganisms. JAMA. 1995;274:1706 1713. 123. Gavald J, Len O, Mir JM, Mu oz P, Montejo M, Alarc n A, de la Torre-Cisneros J, Pe a C, Mart nez-Lacasa X, Sarria C, Bou G, Aguado JM, Navas E, Romeu J, Marco F, Torres C, Tornos P, Planes A, Falc V, Almirante B, PahissaA. Brief communication: treatment of Enterococcus faecalis endocarditis with ampicillin plus ceftriaxone. Ann Intern Med. 2007;146:574 579. 124. Fern ndez-Hidalgo N, Almirante B, Gavald J, Gurgui M, Pe a C, de Alarc n A, Ruiz J, Vilacosta I, Montejo M, Vallejo N, L pez-Medrano F, Plata A, L pez J, Hidalgo-Tenorio C, G lvez J, S ez C, Lomas JM, Falcone M, de la Torre J, Mart nez-Lacasa X, Pahissa A. Ampicillin plus ceftriaxone is as effective as ampicillin plus gentamicin for treating en- terococcus faecalis infective endocarditis. Clin Infect Dis. 2013;56:1261 1268. doi: 10.1093/cid/cit052. 125. Karchmer AW. Staphylococcal endocarditis. In: Kaye D, ed. Infective Endocarditis. 2nd ed. New York, NY: Raven Press; 1992:225 250. 126. Karchmer AW, Gibbons GW. Infection of prosthetic heart valves and vas- cular grafts. In: Bisno AL, Waldvogel FA, eds. Infections Associated With Indwelling Medical Devices. 2nd ed. Washington, DC: American Society for Microbiology; 1994: 213 249. 127. Brown NM, K rner RJ, Zollman CE, Martin RP, Millar MR. Ciprofloxacin treatment of bacterial endocarditis involving prosthetic material after cardiac surgery. Arch Dis Child. 1997;76:68 69. 128. John MD, Hibberd PL, Karchmer AW, Sleeper LA, Calderwood SB. Staphylococcus aureus prosthetic valve endocarditis: optimal manage- ment and risk factors for death. Clin Infect Dis. 1998;26:1302 1309. 129. Stanton BF, Baltimore RS, Clemens JD. Changing spectrum of infec- tive endocarditis in children: analysis of 26 cases, 1970-1979. Am J Dis Child. 1984;138:720 725. 130. Kuyvenhoven JP, van Rijk-Zwikker GL, Hermans J, Thompson J, Huysmans HA. Prosthetic valve endocarditis: analysis of risk factors for mortality. Eur J Cardiothorac Surg. 1994;8:420 424. 131. Wolff M, Witchitz S, Chastang C, R gnier B, Vachon F. Prosthetic valve endocarditis in the ICU: prognostic factors of overall survival in a series of 122 cases and consequences for treatment decision. Chest. 1995;108:688 694. 132. Geraci JE, Wilson WR. Symposium on infective endocarditis, III: en- docarditis due to gram-negative bacteria: report of 56 cases. Mayo Clin Proc. 1982;57:145 148. 133. Baddour LM. Long-term suppressive therapy for Candida parapsilosis- induced prosthetic valve endocarditis. Mayo Clin Proc. 1995;70:773 775. doi: 10.1016/S0025-6196(11)64350-4. 134. Castiglia M, Smego RA, Sames EL. Candida endocarditis and ampho- tericin B intolerance: potential role for fluconazole. Infect Dis Clin Pract. 1994;3:248 53. 135. Wilson WR, Danielson GK, Giuliani ER, Washington JA 2nd, Jaumin PM, Geraci JE. Cardiac valve replacement in congestive heart failure due to infective endocarditis. Mayo Clin Proc. 1979;54:223 226. 136. Richardson JV, Karp RB, Kirklin JW, Dismukes WE. Treatment of infective endocarditis: a 10-year comparative analysis. Circulation. 1978;58:589 597. 137. Stinson EB. Surgical treatment of infective endocarditis. Prog Cardiovasc Dis. 1979;22:145 168. 138. Croft CH, Woodward W, Elliott A, Commerford PJ, Barnard CN, Beck W. Analysis of surgical versus medical therapy in active complicated na- tive valve infective endocarditis. Am J Cardiol. 1983;51:1650 1655. 139. Omari B, Shapiro S, Ginzton L, Robertson JM, Ward J, Nelson RJ, Bayer AS. Predictive risk factors for periannular extension of native valve endocarditis. Clinical and echocardiographic analyses. Chest. 1989;96:1273 1279. 140. McMahon CJ, Ayres N, Pignatelli RH, Franklin W, Vargo TA, Bricker JT, El-Said HG. Echocardiographic presentations of endocarditis, and risk factors for rupture of a sinus of Valsalva in childhood. Cardiol Young. 2003;13:168 172. 141. Carpenter JL. Perivalvular extension of infection in patients with infec- tious endocarditis. Rev Infect Dis. 1991;13:127 138. 142. Rohmann S, Seifert T, Erbel R, Jakob H, Mohr-Kahaly S, Makowski T, G rge G, Oelert H, Meyer J. Identification of abscess formation in native-valve infective endocarditis using transesophageal echocardiog- raphy: implications for surgical treatment. Thorac Cardiovasc Surg. 1991;39:273 280. doi: 10.1055/s-2007-1019985. 143. Nomura F, Penny DJ, Menahem S, Pawade A, Karl TR. Surgical inter- vention for infective endocarditis in infancy and childhood. Ann Thorac Surg. 1995;60:90 95. 144. Jones HR Jr, Siekert RG, Geraci JE. Neurologic manifestations of bacte- rial endocarditis. Ann Intern Med. 1969;71:21 28. 145. Venkatesan C, Wainwright MS. Pediatric endocarditis and stroke: a single-center retrospective review of seven cases. Pediatr Neurol. 2008;38:243 247. doi: 10.1016/j.pediatrneurol.2007.12.009. 146. Niwa K, Nakazawa M, Tateno S, Yoshinaga M, Terai M. Infective en- docarditis in congenital heart disease: Japanese national collaboration study. Heart. 2005;91:795 800. doi: 10.1136/hrt.2004.043323. 147. M gge A, Daniel WG, Frank G, Lichtlen PR. Echocardiography in infec- tive endocarditis: reassessment of prognostic implications of vegetation size determined by the transthoracic and the transesophageal approach. J Am Coll Cardiol. 1989;14:631 638. 148. Saxena A, Aggarwal N, Gupta P, Juneja R, Kothari SS, Math R. Predictors of embolic events in pediatric infective endocarditis. Indian Heart J. 2011;63:237 240. 149. Rohmann S, Erbel R, Darius H, G rge G, Makowski T, Zotz R, Mohr- Kahaly S, Nixdorff U, Drexler M, Meyer J. Prediction of rapid versus prolonged healing of infective endocarditis by monitoring vegetation size. J Am Soc Echocardiogr. 1991;4:465 474. 150. Vuille C, Nidorf M, Weyman AE, Picard MH. Natural history of vegeta- tions during successful medical treatment of endocarditis. Am Heart J. 1994;128(pt 1):1200 1209. 151. Yoshinaga M, Niwa K, Niwa A, Ishiwada N, Takahashi H, Echigo S, Nakazawa M; Japanese Society of Pediatric Cardiology and Cardiac Surgery. Risk factors for in-hospital mortality during infective en- docarditis in patients with congenital heart disease. Am J Cardiol. 2008;101:114 118. doi: 10.1016/j.amjcard.2007.07.054. 152. Kang DH, Kim YJ, Kim SH, Sun BJ, Kim DH, Yun SC, Song JM, Choo SJ, Chung CH, Song JK, Lee JW, Sohn DW. Early surgery ver- sus conventional treatment for infective endocarditis. N Engl J Med. 2012;366:2466 2473. doi: 10.1056/NEJMoa1112843. 153. Botelho-Nevers E, Thuny F, Casalta JP, Richet H, Gouriet F, Collart F, Riberi A, Habib G, Raoult D. Dramatic reduction in infective endocar- ditis-related mortality with a management-based approach. Arch Intern Med. 2009;169:1290 1298. doi: 10.1001/archinternmed.2009.192. 154. Vilacosta I, Graupner C, San Rom n JA, Sarri C, Ronderos R, Fern ndez C, Mancini L, Sanz O, Sanmart n JV, Stoermann W. Risk of embolization after institution of antibiotic therapy for infective endocarditis. J Am Coll Cardiol. 2002;39:1489 1495. 155. Erbel R, Rohmann S, Drexler M, Mohr-Kahaly S, Gerharz CD, Iversen S, Oelert H, Meyer J. Improved diagnostic value of echocardiography in patients with infective endocarditis by transoesophageal approach: a prospective study. Eur Heart J. 1988;9:43 53. 156. Douglas JL, Dismukes WE. Surgical therapy of infective endocarditis on natural valves. In: Kaye D, ed. Infective Endocarditis. 2nd ed. NewYork, NY: Raven Press; 1992:397 412. 157. Citak M, Rees A, Mavroudis C. Surgical management of infective endo- carditis in children. Ann Thorac Surg. 1992;54:755 760. 158. Tolan RW Jr, Kleiman MB, Frank M, King H, Brown JW. Operative in- tervention in active endocarditis in children: report of a series of cases and review. Clin Infect Dis. 1992;14:852 862. 159. Yankah AC, Pasic M, Klose H, Siniawski H, Weng Y, Hetzer R. Homograft reconstruction of the aortic root for endocarditis with perian- nular abscess: a 17-year study. Eur J Cardiothorac Surg. 2005;28:69 75. doi: 10.1016/j.ejcts.2005.03.017. 160. Birk E, Sharoni E, Dagan O, Gelber O, Georghiou GP, Vidne BA, Erez E. The Ross procedure as the surgical treatment of active aortic valve endocarditis. J Heart Valve Dis. 2004;13:73 77. 161. Johnson JA, Boyce TG, Cetta F, Steckelberg JM, Johnson JN. Infective endocarditis in the pediatric patient: a 60-year single-institution review. Mayo Clin Proc. 2012;87:629 635. doi: 10.1016/j.mayocp.2012.02.023. 162. Lalani T, Cabell CH, Benjamin DK, Lasca O, Naber C, Fowler VG Jr, Corey GR, Chu VH, Fenely M, Pachirat O, Tan RS, Watkin R, Ionac A, Baltimore et al Infective Endocarditis in Childhood: 2015 Update 1515 Moreno A, Mestres CA, Casab J, Chipigina N, Eisen DP, Spelman D, Delahaye F, Peterson G, Olaison L, Wang A; International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS) Investigators. Analysis of the impact of early surgery on in-hospital mortality of native valve endocarditis: use of propensity score and instrumental variable methods to adjust for treatment-selection bias. Circulation. 2010;121:1005 1013. doi: 10.1161/CIRCULATIONAHA.109.864488. 163. BannayA, Hoen B, Duval X, Obadia JF, Selton-Suty C, Le MoingV, Tattevin P, Iung B, Delahaye F, Alla F; AEPEI Study Group. The impact of valve sur- gery on short- and long-term mortality in left-sided infective endocarditis: do differences in methodological approaches explain previous conflicting results? Eur Heart J. 2011;32:2003 2015. doi: 10.1093/eurheartj/ehp008. Key Words: AHA Scientific Statements endocarditis pediatrics