In that study,90 the risk of IE per 100 000 patient-years was 4.6 in patients with MVP without an audible cardiac murmur and 52 in patients with MVP with an audible murmur of mitral regurgitation. Per 100 000 patient-years, the lifetime risk (380 to 440) for RHD was similar to that (308 to 383) for patients with a mechanical or bioprosthetic cardiac valve. The highest lifetime risks per 100 000 patient-years were as follows: cardiac valve replacement surgery for native valve IE, 630; previous IE, 740; and prosthetic valve replacement done in patients with prosthetic valve endocarditis, 2160. In a separate study, the risk of IE per 100 000 patient-years was 271 in patients with congenital aortic stenosis and 145 in patients with ventricular septal defect.105 In that same study, the risk of IE before closure of a ventricular septal defect was more than twice that after closure. Although these data provide useful ranges of risk in large populations, it is difficult to utilize them to define accurately the lifetime risk of acquisition of IE in an individual patient with a specific underlying cardiac risk factor. This difficulty is based in part on the fact that each individual cardiac condition, such as RHD or MVP, represents a broad spectrum of pathology from minimal to severe, and the risk of IE would likely be influenced by the severity of valvular disease. CHD is another underlying condition with multiple differ- ent cardiac abnormalities that range from relatively minor to severe, complex cyanotic heart disease. During the past 25 years, there has been an increasing use of various intracardiac valvular prostheses and intravascular shunts, grafts, and other devices for repair of valvular heart disease and CHD. The diversity and nature of these prostheses and procedures likely present different levels of risk for acquisition of IE. These factors complicate an accurate assessment of the true lifetime risk of acquisition of IE in patients with a specific underlying cardiac condition. On the basis of the data from Steckelberg and Wilson91 and others,2 it is clear that the underlying conditions discussed above represent a lifetime increased risk of acquisition of IE compared with individuals with no known underlying cardiac condition. Accordingly, when utilizing previous AHA guide- lines in the decision to recommend IE prophylaxis for a patient scheduled to undergo a dental, GI tract, or GU tract procedure, healthcare providers were required to base their decision on population-based studies of risk of acquisition of IE that may or may not be relevant to their specific patient. Furthermore, practitioners had to weigh the potential efficacy of IE prophylaxis in a patient who may neither need nor benefit from such therapy against the risk of adverse reaction to the antibiotic prescribed. Finally, healthcare providers had to consider the potential medicolegal risk of not prescribing IE prophylaxis. For dental procedures, there is a growing body of evidence that suggests that IE prophylaxis may prevent only an exceedingly small number of cases of IE, as discussed in detail above. Cardiac Conditions Associated With the Highest Risk of Adverse Outcome From Endocarditis Endocarditis, irrespective of the underlying cardiac condition, is a serious, life-threatening disease that was always fatal in the preantibiotic era. Advances in antimicrobial therapy, early recognition and management of complications of IE, and improved surgical technology have reduced the morbidity and mortality of IE. Numerous comorbid factors, such as older age, diabetes mellitus, immunosuppressive conditions or therapy, and dialysis, may complicate IE. Each of these comorbid conditions independently increases the risk of adverse outcome from IE, and they often occur in combina- tion, which further increases morbidity and mortality rates. Additionally, there may be long-term consequences of IE. Over time, the cardiac valve damaged by IE may undergo progressive functional deterioration that may result in the need for cardiac valve replacement. In native valve viridans group streptococcal or enterococcal IE, the spectrum of disease may range from a relatively benign infection to severe valvular dysfunction, dehiscence, congestive heart failure, multiple embolic events, and death; however, the underlying conditions shown in Table 3 virtually always have an increased risk of adverse outcome. For example, patients with viridans group streptococcal prosthetic valve endocarditis have a mortality rate of 20% or greater,106 109 whereas the mortality from patients with viridans group streptococcal native valve IE is 5% or less.108,110 116 Similarly, the mortality of enterococcal prosthetic valve endocarditis is higher than that of native valve enterococcal IE.107,108,114,117 Moreover, patients with prosthetic valve endocarditis are more likely than those with native valve endocarditis to develop heart failure, the need for cardiac valve replacement surgery, perivalvular extension of infection, and other complications. Patients with relapsing or recurrent IE are at greater risk of congestive heart failure and increased need for cardiac valve replacement surgery, and they have a higher mortality rate than patients with a first episode of native valve IE.118 124 Additionally, patients with multiple episodes of native or prosthetic valve IE are at greater risk of additional episodes of endocarditis, each of which is associated with the risk of more Published series regarding endocarditis in patients with CHD are underpowered to determine the extent to which a specific form of CHD is an independent risk factor for morbidity and mortality. Nevertheless, most retrospective case series suggest that patients with complex cyanotic heart disease and those who have postoperative palliative shunts, conduits, or other prostheses have a high lifetime risk of acquiring IE, and these same groups appear at highest risk for morbidity and mortality among all patients with CHD.125 129 In addition, multiple series and reviews reported that the presence of prosthetic material130,131 and complex cyanotic heart disease in patients of very young age (newborns and infants 2 years of age)132,133 are 2 factors associated with the worst prognoses from IE. Some types of CHD may be repaired completely without residual cardiac defects. As shown in Table 3, the Committee concludes that prophylaxis is reasonable for dental procedures for these patients during the first 6 months after the procedure. In these patients, endothelialization of prosthetic material or devices occurs within 6 months after the procedure.134 The Committee does not recommend prophylaxis for dental procedures more than 6 months after the procedure provided that there is no residual defect from the repair. In most instances, treatment of patients who have infected prosthetic materials requires surgical removal in addition to medical therapy with associated high morbidity and mortality rates. Should IE Prophylaxis Be Recommended for Patients With the Highest Risk of Acquisition of IE or for Patients With the Highest Risk of Adverse Outcome From IE? In a major departure from previous AHA guidelines, the Committee no longer recommends IE prophylaxis based solely on an increased lifetime risk of acquisition of IE. It is noteworthy that patients with the conditions listed in Table 3 with a prosthetic cardiac valve, those with a previous episode of IE, and some patients with CHD are also among those patients with the highest lifetime risk of acquisition of endocarditis. No published data demonstrate convincingly that the administration of prophylactic antibiotics prevents IE associated with bacteremia from an invasive procedure. We cannot exclude the possibility that there may be an exceed- ingly small number of cases of IE that could be prevented by prophylactic antibiotics in patients who undergo an invasive procedure. However, if prophylaxis is effective, such therapy should be restricted to those patients with the highest risk of adverse outcome from IE who would derive the greatest benefit from prevention of IE. In patients with underlying cardiac conditions associated with the highest risk of adverse outcome from IE (Table 3), IE prophylaxis for dental proce- Table 3. Cardiac Conditions Associated With the Highest Risk of Adverse Outcome From Endocarditis for Which Prophylaxis With Dental Procedures Is Reasonable Prosthetic cardiac valve or prosthetic material used for cardiac valve repair Previous IE Congenital heart disease (CHD)* Unrepaired cyanotic CHD, including palliative shunts and conduits Completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter intervention, 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 (which inhibit endothelialization) Cardiac transplantation recipients who develop cardiac valvulopathy *Except for the conditions listed above, antibiotic prophylaxis is no longer recommended for any other form of CHD. Prophylaxis is reasonable because endothelialization of prosthetic material occurs within 6 months after the procedure. Wilson et al Prevention of Infective Endocarditis 1745 dures is reasonable, even though we acknowledge that its effectiveness is unknown (Class IIa, LOE B). Compared with previous AHA guidelines, under these revised guidelines, many fewer patients would be candidates to receive IE prophylaxis. We believe that these revised guidelines are in the best interest of patients and healthcare providers and are based on the best available published data and expert opinion. Additionally, the change in emphasis to restrict prophylaxis for only those patients with the highest risk of adverse outcome should reduce the uncertainties among patients and providers about who should receive prophylaxis. MVP is the most common underlying condition that predisposes to acquisition of IE in the Western world; however, the absolute incidence of endocarditis is extremely low for the entire population with MVP, and it is not usually associated with the grave outcome associated with the con- ditions identified in Table 3. Thus, IE prophylaxis is no longer recommended for this group of individuals. Finally, the administration of prophylactic antibiotics is not risk free, as discussed above. Additionally, the widespread use of antibiotic therapy promotes the emergence of resistant microorganisms most likely to cause endocarditis, such as viridans group streptococci and enterococci. The frequency of multidrug-resistant viridans group streptococci and entero- cocci has increased dramatically during the past 2 decades. This increased resistance has reduced the efficacy and num- ber of antibiotics available for the treatment of IE. Antibiotic Regimens General Principles An antibiotic for prophylaxis should be administered in a single dose before the procedure. If the dosage of antibiotic is inadvertently not administered before the procedure, the dosage may be administered up to 2 hours after the procedure. However, administration of the dosage after the procedure should be considered only when the patient did not receive the pre-procedure dose. Some patients who are scheduled for an invasive procedure may have a coincidental endocarditis. The presence of fever or other manifestations of systemic infection should alert the provider to the possibility of IE. In these circumstances, it is important to obtain blood cultures and other relevant tests before administration of antibiotics intended to prevent IE. Failure to do so may result in delay in diagnosis or treatment of a concomitant case of IE. Regimens for Dental Procedures Previous AHA guidelines on prophylaxis listed a substantial number of dental procedures and events for which antibiotic prophylaxis was recommended and those procedures for which prophylaxis was not recommended. On the basis of a critical review of the published data, it is clear that transient viridans group streptococcal bacteremia may result from any dental procedure that involves manipulation of the gingival or periapical region of teeth or perforation of the oral mucosa. It cannot be assumed that manipulation of a healthy-appearing mouth or a minimally invasive dental procedure reduces the likelihood of a bacteremia. Therefore, antibiotic prophylaxis is reasonable for patients with the conditions listed in Table 3 who undergo any dental procedure that involves the gingival tissues or periapical region of a tooth and for those procedures that perforate the oral mucosa (Table 4). Although IE pro- phylaxis is reasonable for these patients, its effectiveness is unknown (Class IIa, LOE C). This includes procedures such as biopsies, suture removal, and placement of orthodontic bands, but it does not include routine anesthetic injections through noninfected tissue, the taking of dental radiographs, placement of removable prosthodontic or orthodontic appli- ances, placement of orthodontic brackets, or adjustment of orthodontic appliances. Finally, there are other events that are not dental procedures and for which prophylaxis is not recommended, such as shedding of deciduous teeth and trauma to the lips and oral mucosa. In this limited patient population, prophylactic antimicro- bial therapy should be directed against viridans group strep- tococci. During the past 2 decades, there has been a signifi- cant increase in the percentage of strains of viridans group streptococci resistant to antibiotics recommended in previous AHA guidelines for the prevention of IE. Prabhu et al135 studied susceptibility patterns of viridans group streptococci recovered from patients with IE diagnosed during a period from 1971 to 1986 and compared these susceptibilities with those of viridans group streptococci from patients with IE diagnosed from 1994 to 2002. In that study, none of the strains of viridans group streptococci were penicillin resistant in the early time period compared with 13% of strains that were intermediately or fully penicillin resistant during the later time period. In that study, macrolide resistance increased from 11% to 26% and clindamycin resistance from 0% to 4%. Among 352 blood culture isolates of viridans group strep- tococci, resistance rates were 13% for penicillin, 15% for amoxicillin, 17% for ceftriaxone, 38% for erythromycin, and 96% for cephalexin.136 The rank order of decreasing level of activity of cephalosporins in that study was cefpodoxime equal to ceftriaxone, greater than cefprozil, and equal to cefuroxime, and cephalexin was the least active. In other studies, resistance of viridans group streptococci to penicillin ranged from 17% to 50%137 142 and resistance to ceftriaxone ranged from 22% to 42%.131,140 Ceftriaxone was 2 to 4 times more active in vitro than cefazolin.131,140 Similarly high rates of resistance were reported for macrolides, ranging from 22% to 58%137,141,143,144; resistance to clindamycin ranged from Most of the strains of viridans group streptococci in the above-cited studies were recovered from patients with serious underlying illnesses, including malignancies and febrile neu- tropenia. These patients are at increased risk of infection and colonization by multiple-drug resistant microorganisms, in- cluding viridans group streptococci. Accordingly, these Table 4. Dental Procedures for Which Endocarditis Prophylaxis Is Reasonable for Patients in Table 3 All dental procedures that involve manipulation of gingival tissue or the periapical region of teeth or perforation of the oral mucosa* *The following procedures and events do not need prophylaxis: routine anesthetic injections through noninfected tissue, taking dental radiographs, placement of removable prosthodontic or orthodontic appliances, adjustment of orthodontic appliances, placement of orthodontic brackets, shedding of deciduous teeth, and bleeding from trauma to the lips or oral mucosa. strains may not be representative of susceptibility patterns of viridans group streptococci recovered from presumably nor- mal individuals who undergo a dental procedure. Diekema et al137 reported that 32% of strains of viridans group strepto- cocci were resistant to penicillin in patients without cancer. King et al144 reported erythromycin resistance in 41% of streptococci recovered from throat cultures in otherwise healthy individuals who presented with mild respiratory tract infections. In that study, after treatment with either azithro- mycin or clindamycin, the percentage of resistant streptococci increased to 82% and 71%, respectively. Accordingly, the resistance rates of viridans group streptococci are similarly high in otherwise healthy individuals and in patients with serious underlying diseases. The impact of viridans group streptococcal resistance on antibiotic prevention of IE is unknown. If resistance in vitro is predictive of lack of clinical efficacy, the high resistance rates of viridans group streptococci provide additional support for the assertion that prophylactic therapy for a dental procedure is of little, if any, value. It is impractical to recommend prophylaxis with only those antibiotics, such as vancomycin or a fluoroquin- olone, that are highly active in vitro against viridans group streptococci. There is no evidence that such therapy is effective for prophylaxis of IE, and their use might result in the develop- ment of resistance of viridans group streptococci and other microorganisms to these and other antibiotics. In Table 5, amoxicillin is the preferred choice for oral therapy because it is well absorbed in the GI tract and provides high and sustained serum concentrations. For indi- viduals who are allergic to penicillins or amoxicillin, the use of cephalexin or another first-generation oral cephalosporin, clindamycin, azithromycin, or clarithromycin is recom- mended. Even though cephalexin was less active against viridans group streptococci than other first-generation oral cephalosporins in 1 study,136 cephalexin is included in Table 5. No data show superiority of 1 oral cephalosporin over another for prevention of IE, and generic cephalexin is widely available and relatively inexpensive. Because of possible cross-reactions, a cephalosporin should not be administered to patients with a history of anaphylaxis, angioedema, or urticaria after treatment with any form of penicillin, including ampicillin or amoxicillin. Patients who are unable to tolerate an oral antibiotic may be treated with ampicillin, ceftriaxone, or cefazolin administered intramuscularly or intravenously. For ampicillin-allergic patients who are unable to tolerate an oral agent, therapy is recommended with parenteral cefazolin, ceftriaxone, or clindamycin. Regimens for Respiratory Tract Procedures A variety of respiratory tract procedures reportedly cause tran- sient bacteremia with a wide array of microorganisms1; how- ever, no published data conclusively demonstrate a link between these procedures and IE. Antibiotic prophylaxis with a regimen listed in Table 5 is reasonable (Class IIa, LOE C) for patients with the conditions listed in Table 3 who undergo an invasive procedure of the respiratory tract that involves incision or biopsy of the respiratory mucosa, such as tonsillectomy and adenoid- ectomy. We do not recommend antibiotic prophylaxis for bronchoscopy unless the procedure involves incision of the respiratory tract mucosa. For patients listed in Table 3 who undergo an invasive respiratory tract procedure to treat an established infection, such as drainage of an abscess or empy- ema, we recommend that the antibiotic regimen administered to these patients contain an agent active against viridans group streptococci (Table 5). If the infection is known or suspected to be caused by Staphylococcus aureus, the regimen should contain an agent active against S aureus, such as an antistaphylococcal penicillin or cephalosporin, or vancomycin in patients unable to tolerate a -lactam. Vancomycin should be administered if the infection is known or suspected to be caused by a methicillin- resistant strain of S aureus. Recommendations for GI or GU Tract Procedures Enterococci are part of the normal flora of the GI tract. These microorganisms may cause intra-abdominal infection or infection of the hepatobiliary system. Such infections are often polymicrobial, with a mix of aerobic and anaerobic Gram-negative and Gram- positive microorganisms, but among these varied bacteria, only enterococci are likely to cause IE. Enterococci may cause urinary Table 5. Regimens for a Dental Procedure Situation Agent Regimen: Single Dose 30 to 60 min Before Procedure Adults Children Oral Amoxicillin 2 g 50 mg/kg Unable to take oral medication Ampicillin OR Cefazolin or ceftriaxone 2 g IM or IV 1 g IM or IV 50 mg/kg IM or IV 50 mg/kg IM or IV Allergic to penicillins or ampicillin oral Cephalexin* OR Clindamycin OR Azithromycin or clarithromycin Allergic to penicillins or ampicillin and unable to take oral medication Cefazolin or ceftriaxone OR Clindamycin 1 g IM or IV 600 mg IM or IV 50 mg/kg IM or IV 20 mg/kg IM or IV IM indicates intramuscular; IV, intravenous. *Or other first- or second-generation oral cephalosporin in equivalent adult or pediatric dosage. Cephalosporins should not be used in an individual with a history of anaphylaxis, angioedema, or urticaria with penicillins or ampicillin. Wilson et al Prevention of Infective Endocarditis 1747 tract infections, particularly in older males with prostatic hypertro- phy and obstructive uropathy or prostatitis. The administration of prophylactic antibiotics solely to pre- vent endocarditis is not recommended for patients who undergo GU or GI tract procedures, including diagnostic esopha- gogastroduodenoscopy or colonoscopy (Class III, LOE B). This is in contrast to previous AHA guidelines that listed GI or GU tract procedures for which IE prophylaxis was recommended and those for which prophylaxis was not recommended.1 A large number of diagnostic and therapeutic procedures that involve the GI, hepatobiliary, or GU tract may cause transient enterococcal bacteremia. The possible association between GI or GU tract proce- dures and IE has not been studied as extensively as the possible association with dental procedures.145 The cases of IE temporally associated with a GI or GU tract proce- dure are anecdotal, with either a single or very small number of cases reported.83 No published data demonstrate a conclusive link between procedures of the GI or GU tract and the development of IE.145 Moreover, no studies exist that demonstrate that the administration of antimicrobial prophylaxis prevents IE in association with procedures performed on the GI or GU tract. There has been a dramatic increase in the frequency of antimicrobial-resistant strains of enterococci to penicillins, vanco- mycin, and aminoglycosides.146 151 These antibiotics were recom- mended for IE prophylaxis in previous AHA guidelines.1 The significance of the increased frequency of multiresistant strains of enterococci on prevention of IE in patients who undergo GI or GU tract procedures is unknown. The high prevalence of resistant strains of enterococci adds further doubt about the efficacy of prophylactic therapy for GI or GU tract procedures. Patients with infections of the GI or GU tract may have intermittent or sustained enterococcal bacteremia. For patients with the conditions listed in Table 3 who have an established GI or GU tract infection or for those who receive antibiotic therapy to prevent wound infection or sepsis associated with a GI or GU tract procedure, it may be reasonable that the antibiotic regimen include an agent active against enterococci, such as penicillin, ampicillin, piperacillin, or vancomycin (Class IIb, LOE B); however, no published studies demonstrate that such therapy would prevent enterococcal IE. For patients with the conditions listed in Table 3 scheduled for an elective cystoscopy or other urinary tract manipulation who have an enterococcal urinary tract infection or coloniza- tion, antibiotic therapy to eradicate enterococci from the urine before the procedure may be reasonable (Class IIb, LOE B). If the urinary tract procedure is not elective, it may be reasonable that the empiric or specific antimicrobial regimen administered to the patient contain an agent active against enterococci (Class IIb, LOE B). Amoxicillin or ampicillin is the preferred agent for entero- coccal coverage for these patients. Vancomycin may be administered to patients unable to tolerate ampicillin. If infection is caused by a known or suspected strain of resistant enterococcus, consultation with an infectious diseases expert is recommended. Regimens for Procedures on Infected Skin, Skin Structure, or Musculoskeletal Tissue These infections are often polymicrobial, but only staphylococci and -hemolytic streptococci are likely to cause IE. For patients with the conditions listed in Table 3 who undergo a surgical procedure that involves infected skin, skin structure, or musculo- skeletal tissue, it may be reasonable that the therapeutic regimen administered for treatment of the infection contain an agent active against staphylococci and -hemolytic streptococci, such as an antistaphylococcal penicillin or a cephalosporin (Table 5 for dosage; Class IIb, LOE C). Vancomycin or clindamycin may be administered to patients unable to tolerate a -lactam or who are known or suspected to have an infection caused by a methicillin- resistant strain of staphylococcus. A summary of the major changes in these updated recom- mendations for prevention of IE compared with previous AHA recommendations is shown in Table 6. Specific Situations and Circumstances Patients Already Receiving Antibiotics If a patient is already receiving long-term antibiotic therapy with an antibiotic that is also recommended for IE prophy- laxis for a dental procedure, it is prudent to select an antibiotic from a different class rather than to increase the dosage of the current antibiotic. For example, antibiotic regimens used to prevent the recurrence of acute rheumatic fever are administered in dosages lower than those recom- mended for the prevention of IE. Individuals who take an oral Table 6. Summary of Major Changes in Updated Document We concluded that bacteremia resulting from daily activities is much more likely to cause IE than bacteremia associated with a dental procedure. We concluded that only an extremely small number of cases of IE might be prevented by antibiotic prophylaxis even if prophylaxis is 100% effective. Antibiotic prophylaxis is not recommended based solely on an increased lifetime risk of acquisition of IE. Limit recommendations for IE prophylaxis only to those conditions listed in Table 3. Antibiotic prophylaxis is no longer recommended for any other form of CHD, except for the conditions listed in Table 3. Antibiotic prophylaxis is reasonable for all dental procedures that involve manipulation of gingival tissues or periapical region of teeth or perforation of oral mucosa only for patients with underlying cardiac conditions associated with the highest risk of adverse outcome from IE (Table 3). Antibiotic prophylaxis is reasonable for procedures on respiratory tract or infected skin, skin structures, or musculoskeletal tissue only for patients with underlying cardiac conditions associated with the highest risk of adverse outcome from IE (Table 3). Antibiotic prophylaxis solely to prevent IE is not recommended for GU or GI tract procedures. Although these guidelines recommend changes in indications for IE prophylaxis with regard to selected dental procedures (see text), the writing group reaffirms that those medical procedures listed as not requiring IE prophylaxis in the 1997 statement remain unchanged and extends this view to vaginal delivery, hysterectomy, and tattooing. Additionally, the committee advises against body piercing for patients with conditions listed in Table 3 because of the possibility of bacteremia, while recognizing that there are minimal published data regarding the risk of bacteremia or endocarditis associated with body piercing. penicillin for secondary prevention of rheumatic fever or for other purposes are likely to have viridans group streptococci in their oral cavity that are relatively resistant to penicillin or amoxicillin. In such cases, the provider should select either clindamycin, azithromycin, or clarithromycin for IE prophy- laxis for a dental procedure, but only for patients shown in Table 3. Because of possible cross-resistance of viridans group streptococci with cephalosporins, this class of antibi- otics should be avoided. If possible, it would be preferable to delay a dental procedure until at least 10 days after comple- tion of the antibiotic therapy. This may allow time for the usual oral flora to be reestablished. Patients receiving parenteral antibiotic therapy for IE may require dental procedures during antimicrobial therapy, particu- larly if subsequent cardiac valve replacement surgery is antici- pated. In these cases, the parenteral antibiotic therapy for IE should be continued and the timing of the dosage adjusted to be administered 30 to 60 minutes before the dental procedure. This parenteral antimicrobial therapy is administered in such high doses that the high concentration would overcome any possible low-level resistance developed among mouth flora (unlike the concentration that would occur after oral administration). Patients Who Receive Anticoagulants Intramuscular injections for IE prophylaxis should be avoided in patients who are receiving anticoagulant therapy (Class I, LOE A). In these circumstances, orally administered regi- mens should be given whenever possible. Intravenously administered antibiotics should be used for patients who are unable to tolerate or absorb oral medications. Patients Who Undergo Cardiac Surgery A careful preoperative dental evaluation is recommended so that required dental treatment may be completed whenever possible before cardiac valve surgery or replacement or repair of CHD. Such measures may decrease the incidence of late prosthetic valve endocarditis caused by viridans group streptococci. Patients who undergo surgery for placement of prosthetic heart valves or prosthetic intravascular or intracardiac mate- rials are at risk for the development of infection.152 Because the morbidity and mortality of infection in these patients are high, perioperative prophylactic antibiotics are recommended (Class I, LOE B). Early-onset prosthetic valve endocarditis is most often caused by S aureus, coagulase-negative staphylo- cocci, or diphtheroids. No single antibiotic regimen is effec- tive against all these microorganisms. Prophylaxis at the time of cardiac surgery should be directed primarily against staphylococci and should be of short duration. A first- generation cephalosporin is most often used, but the choice of an antibiotic should be influenced by the antibiotic suscepti- bility patterns at each hospital. For example, a high preva- lence of infection by methicillin-resistant S aureus should prompt the consideration of the use of vancomycin for perioperative prophylaxis. The majority of nosocomial coagulase-negative staphylococci are methicillin-resistant. Nonetheless, surgical prophylaxis with a first-generation cephalosporin may be recommended for these patients (Class I, LOE A).107 In hospitals with a high prevalence of methicillin-resistant strains of S epidermidis, surgical prophylaxis with vancomycin may be reasonable but has not been shown to be superior to prophylaxis with a cephalosporin (Class IIb, LOE C). Prophylaxis should be initiated immediately before the operative procedure, repeated during prolonged procedures to maintain serum concentrations intraoperatively, and continued for no more than 48 hours postoperatively to minimize emergence of resistant micro- organisms (Class IIa, LOE B). The effects of cardiopulmonary bypass and compromised renal function on antibiotic concentra- tions in serum should be considered and dosages adjusted as necessary before and during the procedure. Other Considerations There is no evidence that coronary artery bypass graft surgery is associated with a long-term risk for infection. Therefore, antibi- otic prophylaxis for dental procedures is not needed for individ- uals who have undergone this surgery. Antibiotic prophylaxis for dental procedures is not recommended for patients with coronary artery stents (Class III, LOE C). The treatment and prevention of infection for these and other endovascular grafts and prosthetic devices are addressed in a separate AHA publi- cation.152 There are insufficient data to support specific recom- mendations for patients who have undergone heart transplanta- tion. Such patients are at risk of acquired valvular dysfunction, especially during episodes of rejection. Endocarditis that occurs in a heart transplant patient is associated with a high risk of adverse outcome (Table 3).153 Accordingly, the use of IE prophylaxis for dental procedures in cardiac transplant recipients who develop cardiac valvulopathy is reasonable, but the useful- ness is not well established (Class IIa, LOE C; Table 4). The use of prophylactic antibiotics to prevent infection of joint prosthe- ses during potentially bacteremia-inducing procedures is not within the scope of this document. Future Considerations Prospective placebo-controlled, double-blinded studies of anti- biotic prophylaxis of IE in patients who undergo a bacteremia- producing procedure would be necessary to evaluate accurately the efficacy of IE prophylaxis. Additional prospective case- control studies are needed. The AHA has made substantial revisions to previously published guidelines on IE prophylaxis. Given our current recommendations, we anticipate that signifi- cantly fewer patients will receive IE prophylaxis for a dental procedure. Studies are necessary to monitor the effects, if any, of these recommended changes in IE prophylaxis. The incidence of IE could change or stay the same. Because the incidence of IE is low, small changes in incidence may take years to detect. Accordingly, we urge that such studies be designed and insti- tuted promptly so that any change in incidence may be detected sooner rather than later. Subsequent revisions of the AHA guidelines on the preven-tion of IE will be based on the results of these studies and other published data. Acknowledgments The writing group thanks the following international experts on infec- tive endocarditis for their valuable comments: Drs Christa Gohlke- Ba rwolf, Roger Hall, Jae-Hoon Song, Catherine Kilmartin, Catherine Leport, Jose M. Miro , Christoph Naber, Graham Roberts, and Jan T.M. van der Meer. The writing group also thanks Dr George Meyer for his helpful comments regarding gastroenterology. Finally, the writing group would like to thank Lori Hinrichs for her superb assistance with the preparation of this manuscript. Wilson et al Prevention of Infective Endocarditis 1749 Disclosures Writing Group Disclosures Writing Group Member Employment Research Grant Other Research Support Speakers Bureau/ Honoraria Ownership Interest Consultant/ Advisory Board Other Walter Wilson Mayo Clinic None None None None None None Larry M. Baddour Mayo Clinic None None None None None None Robert S. Baltimore Yale University School of Medicine None None None None None None Ann Bolger University of California, San Francisco None None None None None None Robert O. Bonow Northwestern University Feinberg School of Medicine None None None None None None Jane C. Burns University of California, San Diego None None None None None None Christopher H. Cabell Duke University National Institutes of Health None None None Gloucester*; Shire*; Cubist*; Carbomedics*; GlaxoSmithKline*; Acusphere*; Endo*; Eli Lilly*; Watson*; Johnson & Johnson* None David T. Durack Becton Dickinson & Co (manufactures medical devices and diagnostics) None None None None Joint Commission Resources Board None Patricia Ferrieri University of Minnesota Medical School None None None None None None Timothy Gardner Christiana Care Health System None None None None None None Michael Gerber Cincinnati Children s Hospital Medical Center None None None None None None Michael Gewitz Maria Fareri Children s Hospital of Westchester, New York Medical College None None None None None None David Goff Wake Forest University School of Medicine None None None None Spriggs & Hollingsworth Law Firm; Scientific Evidence Consulting Firm; GlaxoSmithKline* None Matthew Levison Drexel University College of Medicine None None None None Merck* None Peter B. Lockhart Carolinas Medical Center None None None None None None Jane W. Newburger Boston Children s Heart Foundation None None None None None None Thomas Pallasch University of Southern California None None None None Consultation and expert witness testimony on records of patients with endocarditis None Anne H. Rowley Children s Memorial Hospital, Chicago None None None None None None Stanford T. Shulman Children s Memorial Hospital, Chicago None None None None None None Brian L. Strom University of Pennsylvania School of Medicine Pfizer* Merck*; Novartis*; Wyeth*; Pfizer* None None Abbott*; GlaxoSmithKline*; Eli Lilly*; Pfizer*; Sanofi Pasteur*; Johnson & Johnson*; Schering AG*; Tap Pharma*; Wyeth* None Masato Takahashi University of Southern California Bristol-Myers Squibb Medical Imaging* None None None None None Lloyd Y. Tani University of Utah School of Medicine None None None None None None Kathryn A. Taubert American Heart Association 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 (1) the person receives $10 000 or more during any 12-month period, or 5% or more of the person s gross income; or (2) the person owns 5% or more of the voting stock or share of the entity or owns $10 000 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. References 1. 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 endocarditis: recommendations by the American Heart Asso- ciation. JAMA. 1997;277:1794 1801. 2. Strom BL, Abrutyn E, Berlin JA, Kinman JL, Feldman RS, Stolley PD, Levison ME, Korzeniowski OM, Kaye D. Dental and cardiac risk factors for infective endocarditis: a population-based, case-control study. Ann Intern Med. 1998;129:761 769. 3. Durack DT. Prevention of infective endocarditis. N Engl J Med. 1995; 332:38 44. 4. Durack DT. Antibiotics for prevention of endocarditis during dentistry: time to scale back? Ann Intern Med. 1998;129:829 831. 5. Lockhart PB, Brennan MT, Fox PC, Norton HJ, Jernigan DB, Strausbaugh LJ. Decision-making on the use of antimicrobial pro- phylaxis for dental procedures: a survey of infectious disease consultants and review. Clin Infect Dis. 2002;34:1621 1626. 6. Jones TD, Baumgartner L, Bellows MT, Breese BB, Kuttner AG, McCarty M, Rammelkamp CH (Committee on Prevention of Rheumatic Fever and Bacterial Endocarditis, American Heart Association). Pre- vention of rheumatic fever and bacterial endocarditis through control of streptococcal infections. Circulation. 1955;11:317 320. 7. Rammelkamp CH Jr, Breese BB, Griffeath HI, Houser HB, Kaplan MH, Kuttner AG, McCarty M, Stollerman GH, Wannamaker LW (Committee on Prevention of Rheumatic Fever and Bacterial Endocarditis, American Heart Association). Prevention of rheumatic fever and bacterial endo- carditis through control of streptococcal infections. Circulation. 1957; 15:154 158. 8. Committee on Prevention of Rheumatic Fever and Bacterial Endo- carditis, American Heart Association. Prevention of rheumatic fever and bacterial endocarditis through control of streptococcal infections. Cir- culation. 1960;21:151 155. 9. Wannamaker LW, Denny FW, Diehl A, Jawetz E, Kirby WMM, Markowitz M, McCarty M, Mortimer EA, Paterson PY, Perry W, Ram- melkamp CH Jr, Stollerman GH (Committee on Prevention of Rheumatic Fever and Bacterial Endocarditis, American Heart Association). Prevention of bacterial endocarditis. Circulation. 1965;31:953 954. 10. Rheumatic Fever Committee and the Committee on Congenital Cardiac Defects, American Heart Association. Prevention of bacterial endo- carditis. Circulation. 1972;46:S3 S6. 11. Kaplan EL, Anthony BF, Bisno A, Durack D, Houser H, Millard HD, Sanford J, Shulman ST, Stollerman M, Taranta A, Wenger N (Committee on Rheumatic Fever and Bacterial Endocarditis, American Heart Association). Prevention of bacterial endocarditis. Circulation. 1977;56:139A 143A. 12. Shulman ST, Amren DP, Bisno AL, Dajani AS, Durack DT, Gerber MA, Kaplan EL, Millard HD, Sanders WE, Schwartz RH, Watanaku- nakorn C (Committee on Rheumatic Fever and Infective Endocarditis, American Heart Association). Prevention of bacterial endocarditis: a statement for health professionals by the Committee on Rheumatic Fever and Infective Endocarditis of the Council on Cardiovascular Disease in the Young. Circulation. 1984;70:1123A 1127A. 13. Dajani AS, Bisno AL, Chung KJ, Durack DT, Freed M, Gerber MA, Karchmer AW, Millard HD, Rahimtoola S, Shulman ST, Watanaku- nakorn C, Taubert KA. Prevention of bacterial endocarditis: recommen- dations by the American Heart Association. JAMA. 1990;264: 2919 2922. 14. Selton-Suty C, Duval X, Brochet E, Doco-Lecompte T, Hoen B, Delahaye E, Leport C, Danchin N. New French recommendations for the prophylaxis of infectious endocarditis [in French]. Arch Mal Coeur Vaiss. 2004;97:626 631. 15. Gould FK, Elliott TS, Foweraker J, Fulford M, Perry JD, Robert GJ, Sandoe JA, Watkin RW. Guidelines for the prevention of endocarditis: report of the Working Party of the British Society for Antimicrobial Chemotherapy: authors response. J Antimicrob Chemother. 2006;57: 1035 1042. 16. Ashrafian H, Bogle RG. Antimicrobial prophylaxis for endocarditis: emotion or science? Heart. 2007;93:5 6. 17. Burnette-Curley D, Wells V, Viscount H, Munro CL, Fenno JC, Fives- Taylor P, Macrina FL. FimA, a major virulence factor associated with Streptococcus parasanguis endocarditis. Infect Immun. 1995;63: 4669 4674. 18. Viscount HB, Munro CL, Burnette-Curley D, Peterson DL, Macrina FL. Immunization with FimA protects against Streptococcus parasanguis endocarditis in rats. Infect Immun. 1997;65:994 1002. 19. 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. 20. Durack DT, Beeson PB. Experimental bacterial endocarditis, II: survival of a bacteria in endocardial vegetations. Br J Exp Pathol. 1972;53:50 53. 21. Fowler VG, Scheld WM, Bayer AS. Endocarditis and intravascular infections. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practices of Infectious Diseases. Philadelphia, Pa: Elsevier Churchill Livingstone; 2005:975 1021. 22. Osler W. Gulstonian lectures on malignant endocarditis. lecture I, and lecture II Lancet. 1885;1:415 418, 459 464. 23. Okell CC, Elliott SD. Bacteraemia and oral sepsis: with special reference to the aetiology of subacute endocarditis. Lancet. 1935;2:869 872. Reviewer Disclosures Reviewer Employment Research Grant Other Research Support Speakers Bureau/ Honoraria Expert Witness Ownership Interest Consultant/ Advisory Board Other Thomas Bashore Duke University Medical Center None None None None None None None Arnold Bayer University of California, Los Angeles Titan NIH Cubist June Baker Laird at McElroy, Deutsch, Mulvaney & Carpenter, LLP (Denver, Colo)* None Pfizer* None Donald Falace University of Kentucky None None None None None None None Michael Freed Boston Children s Hospital None None None None None None None Welton Gersony Children s Hospital of New York None None None None None None None Loren Hiratzka Bethesda North Hospital None None None None None None None Patrick O Gara Brigham & Women s Hospital None None None None None None None Lauren L. Patton University of North Carolina None None None None None None None Catherine L. Webb Northwestern University None None None None Amgen 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 (1) the person receives $10 000 or more during any 12-month period, or 5% or more of the person s gross income; or (2) the person owns 5% or more of the voting stock or share of the entity or owns $10 000 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. Wilson et al Prevention of Infective Endocarditis 1751 24. Lockhart PB, Durack DT. Oral microflora as a cause of endocarditis and other distant site infections. Infect Dis Clin North Am. 1999;13: 833 850, vi. 25. 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