prevention of infective endocarditis: guidelines …...prevention of infective endocarditis:...

JADA, Vol. 139 http://jada.ada.org January 2008 3S

Background. The purpose of this statement is toupdate the recommendations by the American HeartAssociation (AHA) for the prevention of infective endo-carditis, which were last published in 1997.Methods and Results. A writing groupappointed by the AHA for their expertise in preventionand treatment of infective endocarditis (IE) withliaison members representing the American DentalAssociation, the Infectious Diseases Society of Americaand the American Academy of Pediatrics. The writinggroup reviewed input from national and international

experts on IE. The recommendations in this document reflectanalyses of relevant literature regarding procedure-relatedbacteremia and IE; in vitro susceptibility data of the mostcommon microorganisms, which cause IE; results of prophy-lactic studies in animal models of experimental endocarditis;and retrospective and prospective studies of prevention of IE.MEDLINE database searches from 1950 through 2006 weredone for English language articles using the following searchterms: endocarditis, infective endocarditis, prophylaxis, pre-vention, antibiotic, antimicrobial, pathogens, organisms,dental, gastrointestinal, genitourinary, streptococcus, entero-

Prevention of infective endocarditis: Guidelines from the American Heart AssociationA guideline from the American Heart Association Rheumatic Fever, Endocarditis and Kawasaki Disease Committee, Council on CardiovascularDisease 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

Walter Wilson, MD; Kathryn A. Taubert, PhD, FAHA; Michael Gewitz, MD, FAHA; Peter B. Lockhart, DDS; Larry M. Baddour, MD; Matthew Levison, MD; Ann Bolger, MD, FAHA;Christopher H. Cabell, MD, MHS; Masato Takahashi, MD, FAHA; Robert S. Baltimore, MD; Jane W. Newburger, MD, MPH, FAHA; Brian L. Strom, MD; Lloyd Y. Tani, MD; Michael Gerber, MD;Robert O. Bonow, MD, FAHA; Thomas Pallasch, DDS, MS; Stanford T. Shulman, MD, FAHA; Anne H. Rowley, MD; Jane C. Burns, MD; Patricia Ferrieri, MD; Timothy Gardner, MD, FAHA;David Goff, MD, PhD, FAHA; David T. Durack, MD, PhD

A B S T R A C T

The Council on Scientific Affairs of the American Dental Association has approved these guidelines as they relate todentistry.

Copyright ©2008 American Dental Association. All rights reserved.

4S JADA, Vol. 139 http://jada.ada.org January 2008

Infective endocarditis (IE) is an uncommonbut life-threatening infection. Despiteadvances in diagnosis, antimicrobialtherapy, surgical techniques and manage-ment of complications, patients with IE

still have substantial morbidity and mortalityrelated to this condition. Since the last AmericanHeart Association (AHA) publication on preven-tion of IE in 1997,1 many authorities, societiesand the conclusions of published studies havequestioned the efficacy of antimicrobial prophy-laxis to prevent IE in patients who undergo adental, gastrointestinal (GI) or genitourinary(GU) tract procedure and have suggested thatthe AHA guidelines should be revised.2-5 Mem-bers of the Rheumatic Fever, Endocarditis andKawasaki Disease Committee of the AHACouncil on Cardiovascular Disease in the Young

coccus, staphylococcus, respiratory, dental surgery,pathogenesis, vaccine, immunization and bacteremia.The reference lists of the identified articles were alsosearched. The writing group also searched the AHAonline library. The American College of Cardiology/AHAclassification of recommendations and levels of evidencefor practice guidelines were used. The article subse-quently was reviewed by outside experts not affiliatedwith the writing group and by the AHA Science Advi-sory and Coordinating Committee.Conclusions. The major changes in the updated rec-ommendations include the following. (1) The committeeconcluded that only an extremely small number of casesof IE might be prevented by antibiotic prophylaxis fordental procedures even if such prophylactic therapywere 100 percent effective. (2) IE prophylaxis for dentalprocedures should be recommended only for patientswith underlying cardiac conditions associated with the

highest risk of adverse outcome from IE. (3) Forpatients with these underlying cardiac conditions, pro-phylaxis is recommended for all dental procedures thatinvolve manipulation of gingival tissue or the peri-apical region of teeth or perforation of the oral mucosa.(4) Prophylaxis is not recommended based solely on anincreased lifetime risk of acquisition of IE. (5) Adminis-tration of antibiotics solely to prevent endocarditis isnot recommended for patients who undergo a geni-tourinary or gastrointestinal tract procedure. Thesechanges are intended to define more clearly when IEprophylaxis is or is not recommended and to providemore uniform and consistent global recommendations.Key Words. AHA Scientific Statements; cardiovas-cular disease; endocarditis; prevention; antibiotic prophylaxis.JADA 2008;139(1):3S-24S.

ABBREVIATION KEY. ACC: American College of Cardiology. ADA: American Dental Association. AHA:American Heart Association. CFU: Colony-formingunit. CHD: Congenital heart disease. FimA: Fimbrialadhesion protein. GI: Gastrointestinal. GU: Genitouri-nary. IE: Infective endocarditis. LOE: Level of evi-dence. MVP: Mitral valve prolapse. NBTE: Nonbacte-rial thrombotic endocarditis. PVE: Prosthetic valveendocarditis. RHD: Rheumatic heart disease.

Editor’s note: Of the complete text of Prevention ofInfective Endocarditis: Guidelines From the AmericanHeart Association—A Guideline From the AmericanHeart Association Rheumatic Fever, Endocarditis andKawasaki Disease Committee, Council on Cardiovas-cular Disease in the Young, and the Council on ClinicalCardiology, Council on Cardiovascular Surgery andAnesthesia, and the Quality of Care and OutcomesResearch Interdisciplinary Working Group, the fol-lowing text represents the portions that are pertinentto dentistry. The American Dental Association Councilon Scientific Affairs has approved these guidelines asthey relate to dentistry. These guidelines have beenendorsed by the Infectious Diseases Society of Americaand by the Pediatric Infectious Diseases Society.

Throughout this article, readers will see referencesto gastrointestinal, genitourinary and respiratorytract procedures; surgical procedures that involveinfected skin, skin structures or musculoskeletaltissue; and some types of cardiac surgery. Reference tothese conditions has been retained in this version ofthe American Heart Association (AHA) antibiotic pro-phylaxis recommendations directed toward dentistrybecause of the historical context of their inclusion bythe AHA. However, the sections of the original AHAPrevention of Infective Endocarditis Guidelines thatgo into detail on these conditions have been removedfrom this article. Interested readers should consult thecomplete AHA Guidelines available at “http://circ.ahajournals.org/cgi/content/full/116/15/1736”.



(the Committee), and a national and interna-tional group of experts on IE extensivelyreviewed data published on the prevention of IE.The revised guidelines for IE prophylaxis are thesubject of this report.

The writing group was charged with the taskof performing an assessment of the evidence andgiving a classification of recommendations and alevel of evidence (LOE) to each recommendation.The American College of Cardiology (ACC)/AHAclassification system was used (Box 1).6

HISTORY OF AMERICAN HEART ASSOCIATION STATEMENTS ON PREVENTION OF INFECTIVE ENDOCARDITIS

The AHA has made recommendations for the pre-vention of IE for more than 50 years. In 1955, thefirst AHA document was published in Circula-tion.7 Table 1 shows a summary of the documentspublished from 1955 through 1997.1,7-14 The 1960document called attention to the possible emer-gence of penicillin-resistant oral microflora as aresult of prolonged therapy for prevention of IE,and pediatric patients were included for the firsttime.9 Chloramphenicol was recommended forpatients allergic to penicillin. In 1965, the Com-mittee published for the first time a documentdevoted solely to the prophylaxis of IE and recog-nized the importance of enterococci after GI orGU tract procedures.10 The revised recommenda-tions published in 1972 were endorsed for thefirst time by the American Dental Association(ADA) and emphasized the importance of mainte-nance of good oral hygiene.11 This version intro-duced a recommendationfor ampicillin in patientsundergoing a GI or GUtract procedure. The 1977revisions categorized bothpatients and proceduresinto high- and low-riskgroups.12 This resulted incomplex tables with manyfootnotes. The duration ofpostprocedure therapy wasreduced from two days totwo doses. The 1984 rec-ommendations attemptedto simplify prophylacticregimens by providingclear lists of procedures forwhich prophylaxis was

and was not recommended and reduced postproce-dure prophylaxis for dental, GI and GU tract pro-cedures to only one oral or parenteral dose.13 In1990, a more complete list of cardiac conditionsand dental or surgical procedures for which pro-phylaxis was and was not recommended was pro-vided.14 These previous recommendations recog-nized the potential medicolegal risks associatedwith IE prophylaxis and suggested that the rec-ommendations were intended to serve as a guide-line, not as established standard of care. The mostrecent AHA document on IE prophylaxis was pub-lished in 1997.1 The 1997 document stratified car-diac conditions into high-, moderate- and low-risk(negligible risk) categories with prophylaxis notrecommended for the low-risk group.1 An evenmore detailed list of dental, respiratory, GI andGU tract procedures for which prophylaxis wasand was not recommended was provided. The1997 document was notable for its acknowledg-ment that most cases of IE are not attributable toan invasive procedure but rather are the result ofrandomly occurring bacteremias from routinedaily activities and for acknowledging possible IEprophylaxis failures.

RATIONALE FOR REVISING THE 1997DOCUMENT

It is clear from the above chronology that theAHA guidelines for IE prophylaxis have been in aprocess of evolution for more than 50 years. Therationale for prophylaxis was based largely onexpert opinion and what seemed to be a rationaland prudent attempt to prevent a life-threateninginfection. On the basis of the ACC and AHA Task

Classification of recommendations and levels of evidence.*CLASSIFICATION OF RECOMMENDATIONSClass I Conditions for which there is evidence and/or general agreement that

a given procedure or treatment is useful and effectiveClass II Conditions for which there is conflicting evidence and/or a divergence

of opinion about the usefulness or efficacy of a procedure or treatmentIIa Weight of evidence/opinion is in favor of usefulness/efficacyIIb Usefulness/efficacy is less well-established by evidence/opinion

Class III Conditions for which there is evidence and/or general agreement that the procedure or treatment is not useful or effective and, in some cases, may be harmful

LEVEL OF EVIDENCEA Data derived from multiple randomized clinical trials or meta-analysisB Data derived from a single randomized trial or from nonrandomized studiesC Only consensus opinion of experts, case studies or standard of care

* Adapted from the American College of Cardiology Foundation and American Heart Association TaskForce on Practice Guidelines.6

BOX 1


Force on Practice Guidelines’ evidence-basedgrading system for ranking recommendations, therecommendations in the AHA documents pub-lished during the last 50 years would be ClassIIb, LOE C. Accordingly, the basis for recommen-dations for IE prophylaxis was not well-estab-lished, and the quality of evidence was limited toa few case-control studies or was based on expertopinion, clinical experience and descriptivestudies, which used surrogate measures of risk.

Over the years, other international societieshave published recommendations and guidelinesfor the prevention of IE.15,16 Recently, the British

Society for Antimicrobial Chemo-therapy issued new IE prophylaxis recommendations.16 This group now recommends prophylaxis before dentalprocedures only for patients who have ahistory of previous IE or who have hadcardiac valve replacement or surgicallyconstructed pulmonary shunts or conduits.

Fundamental underlying principlesthat drove the formulation of the AHAguidelines and the nine previous AHAdocuments were that (1) IE is anuncommon but life-threatening diseaseand prevention is preferable to treat-ment of established infection; (2) cer-tain underlying cardiac conditions pre-dispose to IE; (3) bacteremia withorganisms known to cause IE occurscommonly in association with invasivedental, GI or GU tract procedures; (4)antimicrobial prophylaxis was provento be effective for prevention of experi-mental IE in animals; and (5) antimi-crobial prophylaxis was thought to beeffective in humans for prevention of IEassociated with dental, GI or GU tractprocedures. The Committee believesthat of these five underlying principles,the first four are valid and have notchanged during the past 30 years.Numerous publications questioned thevalidity of the fifth principle and sug-gested revision of the guidelines, pri-marily for reasons shown in Box 2.

Another reason that led the Com-mittee to revise the 1997 document wasthat over the past 50 years, the AHAguidelines on prevention of IE becameoverly complicated, making it difficult

for patients and health care providers to interpretor remember specific details, and they containedambiguities and some inconsistencies in the rec-ommendations. The decision to substantiallyrevise the 1997 document was not taken lightly.The present revised document was not based onthe results of a single study but rather on the col-lective body of evidence published in numerousstudies over the past two decades. The Committeesought to construct the present recommendationssuch that they would be in the best interest ofpatients and providers, would be reasonable andprudent, and would represent the conclusions of


TABLE 1

Summary of nine iterations of AmericanHeart Association–recommended antibioticregimens* from 1955 to 1997 for dental/respiratory tract procedures.YEAR PRIMARY REGIMENS FOR DENTAL PROCEDURES

* These regimens were for adults and represented the initial regimen listed in each ver-sion of the recommendations. In some versions, more than one regimen was included.

† IM: Intramuscularly.

19557

19578

19609

196510

197211

197712

198413

199014

19971

Aqueous penicillin 600,000 units IM† and procaine penicillinin oil containing 2 percent aluminum monostearate 600,000U IM administered 30 minutes before the operative procedure.

For two days before surgery, penicillin 200,000 to 250,000 Uby mouth four times per day. On day of surgery, penicillin200,000 to 250,000 U by mouth four times per day andaqueous penicillin 600,000 U with procaine penicillin600,000 U IM 30 to 60 minutes before surgery. For two daysafter, 200,000 to 250,000 U by mouth four times per day.

Step I: prophylaxis two days before surgery with procainepenicillin 600,000 U IM on each day.Step II: day of surgery: procaine penicillin 600,000 U IMsupplemented by crystalline penicillin 600,000 U IM onehour before surgical procedure.Step III: for two days after surgery: procaine penicillin600,000 U IM each day.

Day of procedure: Procaine penicillin 600,000 U, supplemented by crystalline penicillin 600,000 U IM one to two hours before the procedure.For two days after procedure: procaine penicillin 600,000 UIM each day.

Procaine penicillin G 600,000 U mixed with crystalline penicillin G 200,000 U IM one hour before procedure andonce daily for the two days after the procedure.

Aqueous crystalline penicillin G 1,000,000 U IM mixed withprocaine penicillin G 600,000 U IM. Give 30 minutes to one hour before procedure and then give penicillin V 500milligrams orally every two hours for eight doses.

Penicillin V 2 grams orally one hour before; then 1 g six hours after initial dose.

Amoxicillin 3 g orally one hour before procedure; then 1.5 g six hours after initial dose.

Amoxicillin 2 g orally one hour before procedure.


published studies and the collective wisdom ofmany experts on IE and relevant national andinternational societies.

POTENTIAL CONSEQUENCES OF SUBSTANTIVE CHANGES IN RECOMMENDATIONS

Substantive changes in recommendations could(1) violate long-standing expectations and prac-tice patterns, (2) make fewer patients eligible forIE prophylaxis, (3) reduce malpractice claimsrelated to IE prophylaxis and (4) stimulateprospective studies on IE prophylaxis. The Com-mittee and Ashrafian and Bogle17 recognize thatsubstantive changes in IE prophylaxis guidelinesmay violate long-standing expectations of andpractice patterns by patients and health careproviders. The Committee recognizes that thesenew recommendations may cause concern amongpatients who have previously taken antibioticprophylaxis to prevent IE before dental or otherprocedures and are now advised that such pro-phylaxis is unnecessary. Box 2 includes the maintalking points that may be helpful for cliniciansin re-educating their patients regarding thesechanges. To recommend such changes demandsdue diligence and critical analysis. For 50 years,since the publication of the first AHA guidelineson the prevention of IE,7 patients and health careproviders assumed that antibiotics administeredin association with a bacteremia-producing pro-cedure effectively prevented IE in patients withunderlying cardiac risk factors. Patients wereeducated about bacteremia-producing proceduresand risk factors for IE, and they expected toreceive antibiotic prophylaxis; health careproviders, especially dentists, were expected toadminister them. Patients with underlying car-diac conditions that have alifetime risk of acquisitionof IE, such as mitral valveprolapse (MVP), had asense of reassurance andcomfort that antibioticsadministered in associa-tion with a dental pro-cedure was effective andusually safe to prevent IE.Health care providers,especially dentists, felt asense of obligation andprofessional and legalresponsibility to protect

their patients from IE that might result from aprocedure. On the basis of recommendations inthis revised document, substantially fewerpatients will be recommended for IE prophylaxis.

Cases of IE either temporally or remotely asso-ciated with an invasive procedure, especially adental procedure, have frequently been the basisfor malpractice claims against health careproviders. Unlike many other infections for whichthere is conclusive evidence for the efficacy of pre-ventive therapy, the prevention of IE is not a pre-cise science. Because previously published AHAguidelines for the prevention of IE containedambiguities and inconsistencies and often werebased on minimal published data or expertopinion, they were subject to conflicting inter-pretations among patients, health care providersand the legal system about patient eligibility forprophylaxis and whether there was strict adher-ence by health care providers to AHA recommen-dations for prophylaxis. This document isintended to identify which, if any, patients maypossibly benefit from IE prophylaxis and todefine, to the extent possible, which dental pro-cedures should have prophylaxis in this selectgroup of patients. Accordingly, the Committeehopes that this document will result in greaterclarity for patients, health care providers andconsulting professionals.

The Committee believes that recommendationsfor IE prophylaxis must be evidence-based. Aplacebo-controlled, multicenter, randomized,double-blinded study to evaluate the efficacy of IEprophylaxis in patients who undergo a dental, GIor GU tract procedure has not been done. Such astudy would require a large number of patientsper treatment group and standardization of the


Primary reasons for revision of the infective endocarditis prophylaxis guidelines.

dInfective endocarditis (IE) is much more likely to result from frequent exposureto random bacteremias associated with daily activities than from bacteremiacaused by a dental, gastrointestinal (GI) tract or genitourinary (GU) tract procedure

dProphylaxis may prevent an exceedingly small number of cases of IE, if any, inpeople who undergo a dental, GI tract or GU tract procedure

dThe risk of antibiotic-associated adverse events exceeds the benefit, if any, fromprophylactic antibiotic therapy

dMaintenance of optimal oral health and hygiene may reduce the incidence ofbacteremia from daily activities and is more important than prophylacticantibiotics for a dental procedure to reduce the risk of IE

BOX 2


specific invasive procedures and the patient popu-lations. This type of study would be necessary toanswer definitively long-standing unresolvedquestions regarding the efficacy of IE prophy-laxis. The Committee hopes that this reviseddocument will stimulate additional studies on theprevention of IE. Future published data will bereviewed carefully by the AHA Rheumatic Fever,Endocarditis and Kawasaki Disease Committee,and other societies, and further revisions to thecurrent document will be based on relevantstudies.

PATHOGENESIS OF INFECTIVE ENDOCARDITIS

The development of IE is the net result of thecomplex interaction between the bloodstreampathogen with matrix molecules and platelets atsites of endocardial cell damage. In addition,many of the clinical manifestations of IE emanatefrom the host’s immune response to the infectingmicroorganism. The following sequence of eventsis thought to result in IE: formation of nonbacte-rial thrombotic endocarditis (NBTE) on the sur-face of a cardiac valve or elsewhere that endothe-lial damage occurs, bacteremia, adherence of thebacteria in the bloodstream to NBTE and prolifer-ation of bacteria within a vegetation.

Formation of NBTE. Turbulent blood flowproduced by certain types of congenital oracquired heart disease, such as flow from a high-to a low-pressure chamber or across a narrowedorifice, traumatizes the endothelium. This createsa predisposition for deposition of platelets andfibrin on the surface of the endothelium, whichresults in NBTE. Invasion of the bloodstream witha microbial species that has the pathogenic poten-tial to colonize this site can then result in IE.

Transient bacteremia. Mucosal surfaces arepopulated by a dense endogenous microflora.Trauma to a mucosal surface, particularly thegingival crevice around teeth, oropharynx, GItract, urethra or vagina, releases many differentmicrobial species transiently into the blood-stream. Transient bacteremia caused by viridansgroup streptococci and other oral microfloraoccurs commonly in association with dentalextractions or other dental procedures or withroutine daily activities. Although controversial,the frequency and intensity of the resulting bac-teremias are believed to be related to the natureand magnitude of the tissue trauma, the densityof the microbial flora and the degree of inflamma-

tion or infection at the site of trauma. The micro-bial species entering the circulation depends onthe unique endogenous microflora that colonizesthe particular traumatized site.

Bacterial adherence. The ability of variousmicrobial species to adhere to specific sites deter-mines the anatomical localization of infectioncaused by these microorganisms. Mediators of bac-terial adherence serve as virulence factors in thepathogenesis of IE. Numerous bacterial surfacecomponents present in streptococci, staphylococciand enterococci have been shown in animalmodels of experimental endocarditis to function ascritical adhesins. Some viridans group streptococcicontain a fimbrial adhesion protein (FimA), whichis a lipoprotein receptor antigen I that serves as amajor adhesin to the fibrin platelet matrix ofNBTE.18 Staphylococcal adhesins function in atleast two ways. In one, microbial surface compo-nents recognizing adhesive matrix molecules facil-itate the attachment of staphylococci to humanextracellular matrix proteins and to medicaldevices, which become coated with matrix proteinsafter implantation. In the other, bacterial extra-cellular structures contribute to the formation ofbiofilm, which forms on the surface of implantedmedical devices. In both cases, staphylococcaladhesins are important virulence factors.

Both FimA and staphylococcal adhesins areimmunogenic in experimental infections. Vaccinesprepared against FimA and staphylococcaladhesins provide some protective effect in experi-mental endocarditis caused by viridans groupstreptococci and staphylococci.19,20 The results ofthese experimental studies are highly intriguing,because the development of an effective vaccinefor use in humans to prevent viridans groupstreptococcal or staphylococcal IE would be ofmajor importance.

Proliferation of bacteria within a vegeta-tion. Microorganisms adherent to the vegetationstimulate further deposition of fibrin andplatelets on their surface. Within this secludedfocus, the buried microorganisms multiply asrapidly as do bacteria in broth cultures to reachmaximal microbial densities of 108 to 1011 colony-forming units (CFUs) per gram of vegetationwithin a short time on the left side of the heart,apparently uninhibited by host defenses in left-sided lesions. Right-sided vegetations have lowerbacterial densities, which may be the consequenceof host defense mechanisms active at this site,such as polymorphonuclear activity or platelet-

8S JADA, Vol. 139 http://jada.ada.org January 2008Copyright ©2008 American Dental Association. All rights reserved.

derived antibacterial proteins. More than 90 per-cent of the microorganisms in mature left- orright-sided valvular vegetations are metabolicallyinactive, rather than in an active growth phase,and are, therefore, less responsive to the bacteri-cidal effects of antibiotics.21

RATIONALE FOR OR AGAINST PROPHYLAXIS OF INFECTIVE ENDOCARDITIS

Historical background. Viridans group strepto-cocci are part of the normal skin, oral, respiratoryand GI tract flora, and they cause at least 50 per-cent of cases of community-acquired native valveIE not associated with intravenous drug use.22

More than a century ago, the oral cavity was rec-ognized as a potential source of thebacteremia that caused viridansgroup streptococcal IE. In 1885,Osler23 noted an associationbetween bacteremia from surgeryand IE. Okell and Elliott24 in 1935reported that 11 percent of patientswith poor oral hygiene had positiveblood cultures with viridans groupstreptococci, and that 61 percent ofpatients had viridans group strep-tococcal bacteremia with dentalextraction.

As a result of these early andsubsequent studies, during the past50 years the AHA guidelines recom-mended antimicrobial prophylaxis to prevent IEin patients with underlying cardiac conditionswho underwent bacteremia-producing proceduresbased on the following factors: (1) bacteremiacauses endocarditis; (2) viridans group strepto-cocci are part of the normal oral flora and entero-cocci are part of the normal GI and GU tract flora;(3) these microorganisms were usually susceptibleto antibiotics recommended for prophylaxis; (4)antibiotic prophylaxis prevents viridans groupstreptococcal or enterococcal experimental endo-carditis in animals; (5) a large number of poorlydocumented case reports implicated a dental pro-cedure as a cause of IE; (6) in some cases, therewas a temporal relationship between a dentalprocedure and the onset of symptoms of IE; (7) anawareness of bacteremia caused by viridansgroup streptococci associated with a dental pro-cedure exists; (8) the risk of significant adversereactions to an antibiotic is low in an individualpatient; and (9) morbidity and mortality of IE are

high. Most of these factors remain valid, but col-lectively they do not compensate for the lack ofpublished data that demonstrate a benefit fromprophylaxis.

Bacteremia-producing dental procedures.The large majority of published studies havefocused on dental procedures as a cause of IE andthe use of prophylactic antibiotics to prevent IE inpatients at risk. Few data exist on the risk of orprevention of IE associated with a GI or GU tractprocedure. Accordingly, the Committee undertooka critical analysis of published data in the contextof the historical rationale for recommendingantibiotic prophylaxis for IE before a dental pro-cedure. The following factors were considered: (1) frequency, nature, magnitude and duration of

bacteremia associated with dentalprocedures; (2) impact of dental dis-ease, oral hygiene and type ofdental procedure on bacteremia; (3) impact of antibiotic prophylaxison bacteremia from a dental pro-cedure; and (4) the exposure overtime of frequently occurring bac-teremia from routine daily activi-ties compared with bacteremia fromvarious dental procedures.

Frequency, nature, magnitudeand duration of bacteremia asso-ciated with a dental procedure.Transient bacteremia is commonwith manipulation of the teeth and

periodontal tissues, and there is a wide variationin reported frequencies of bacteremia in patientsresulting from dental procedures: tooth extraction(10-100 percent), periodontal surgery (36-88 per-cent), scaling and root planing (8-80 percent),teeth cleaning (up to 40 percent), rubber dammatrix/wedge placement (9-32 percent) andendodontic procedures (up to 20 percent).25-31

Transient bacteremia also occurs frequentlyduring routine daily activities unrelated to adental procedure: tooth brushing and flossing (20-68 percent), use of wooden toothpicks (20-40 per-cent), use of water irrigation devices (7-50 per-cent) and chewing food (7-51 percent).27-30,32-37

Considering that the average person living in theUnited States has fewer than two dental visitsper year, the frequency of bacteremia from rou-tine daily activities is far greater.

There has been a disproportionate focus on thefrequency of bacteremia associated with dentalprocedures rather than the species of bacteria


Available evidencesupports an emphasison maintaining good

oral hygiene and eradicating dental disease to decrease

the frequency ofbacteremia from

routine dailyactivities.



Editor’s note: The following statement isintended as a companion to the 2007American Heart Association (AHA) guide-lines for prevention of infective endocarditisreprinted in this supplement. When refer-ring to the AHA guidelines, readers alsoshould consult this statement.

The American Heart Association(AHA)1 states that its document“Prevention of Infective Endo-carditis: Guidelines From theAmerican Heart Association” was

developed through an evidence-basedapproach and attempts to reduce ambigui-ties about the patients for whom antibioticprophylaxis may be indicated and underwhat conditions, as well as what antibioticsto use. Dentists should be aware that, whilethe precise standard of care may vary basedon locale, the guidelines likely will be citedas some evidence of the standard of care inany malpractice litigation. Nonetheless, it isthe American Dental Association’s recom-mendation that a dentist exercise indepen-dent professional judgment in applyingthese or any other guidelines as necessary inany clinical situation.

Should the patient present a recommen-dation from a treating physician with whichthe dentist disagrees, the dentist may wishto consult with the physician, as the goal intreatment should be to reach consensusamong professionals. Communicationbetween professionals should provide infor-mation about the bases for the physician’srecommendations and why the dentist disagrees.

If consensus on treatment cannot bereached, the answer may lie in informed con-sent, which usually can be relied on to pro-tect the practitioner who respects thepatient’s treatment decisions from legal lia-bility as long as the treatment is within thestandard of care. To be effective, thepatient’s consent must be given after all rea-sonable treatment options and each option’sbenefits and risks are fully disclosed. Whentreatment consensus among treating profes-sionals is absent, it is prudent also to dis-close that the treatment recommendationsdiffer and to encourage the patient to dis-cuss treatment options with the physicianbefore making a decision regarding treat-ment. The dentist should note or copy allcommunications regarding treatmentoptions.

It should be remembered that the dentistand not the patient ultimately is responsiblefor patient treatment. The dentist, therefore,is not obligated to perform a treatment he orshe does not believe to be in the best inter-ests of the patient.

The above information should not be con-strued as legal advice or a standard of care.A practitioner always should consult his orher own attorney for answers to specificlegal questions. ■

1. Wilson W, Taubert KA, Gewitz M, et al. Prevention of infec-tive endocarditis: guidelines from the American Heart Associa-tion—a guideline from the American Heart AssociationRheumatic Fever, Endocarditis and Kawasaki Disease Com-mittee, Council on Cardiovascular Disease in the Young, andthe Council on Clinical Cardiology, Council on CardiovascularSurgery and Anesthesia, and the Quality of Care and OutcomesResearch Interdisciplinary Working Group. Circulation2007;116:1736-54.

An updated legal perspective on antibiotic prophylaxisAmerican Dental Association Division of Legal Affairs


recovered from blood cultures. Studies suggestthat more than 700 species of bacteria, includingaerobic and anaerobic gram-positive and gram-negative microorganisms, may be identified in thehuman mouth, particularly on the teeth and inthe gingival crevices.25,38-41 Approximately 30 per-cent of the flora of the gingival crevice is strepto-cocci, predominantly of the viridans group. Of themore than 100 oral bacterial species recoveredfrom blood cultures after dental procedures, themost prevalent of these are viridans group strep-tococci, the most common microbiological cause ofcommunity-acquired native valve IE in nonintra-venous drug users.22 In healthy mouths, a thinsurface of mucosal epithelium separates poten-tially pathogenic bacteria from entering thebloodstream and lymphatic system. Anaerobicmicroorganisms commonly are responsible forperiodontal disease and frequently enter thebloodstream but rarely cause IE, with fewer than120 cases reported.42 Viridans group streptococciare antagonistic to periodontal pathogens andpredominate in a clean, healthy mouth.43

Few published studies exist on the magnitudeof bacteremia after a dental procedure or fromroutine daily activities, and most of the publisheddata used older, often unreliable microbiologicalmethodology. There are no published data thatdemonstrate that a greater magnitude of bac-teremia, compared with a lower magnitude, ismore likely to cause IE in humans. The magni-tude of bacteremia resulting from a dental pro-cedure is relatively low (< 104 CFUs of bacteriaper milliliter), similar to that resulting from rou-tine daily activities, and is less than that used tocause experimental IE in animals (106-108 CFUsof bacteria/mL).21,44,45 Although the infective doserequired to cause IE in humans is unknown, thenumber of microorganisms in blood after a dentalprocedure or associated with daily activities islow. Cases of IE caused by oral bacteria probablyresult from the exposures to low inocula of bac-teria in the bloodstream that result from routinedaily activities and not from a dental procedure.Additionally, the vast majority of patients with IEhave not had a dental procedure within twoweeks before the onset of symptoms of IE.2-4

The role of duration of bacteremia on the riskof acquisition of IE is uncertain.46,47 Early studiesreported that sequential blood cultures were posi-tive for up to 10 minutes after tooth extractionand that the number of positive blood culturesdropped sharply after 10 to 30 minutes.25,46-52 More

recent studies support these data but report asmall percentage of positive blood cultures from30 to 60 minutes after tooth extraction.44,53,54 Intu-itively, it seems logical to assume that the longerthe duration of bacteremia, the greater the risk ofIE, but no published studies support this assump-tion. Given the preponderance of published data,there may not be a clinically significant differencein the frequency, nature, magnitude and durationof bacteremia associated with a dental procedurecompared with that resulting from routine dailyactivities. Accordingly, it is inconsistent to recom-mend prophylaxis of IE for dental procedures butnot for these same patients during routine dailyactivities. Such a recommendation for prophylaxisfor routine daily activities would be impracticaland unwarranted.

Impact of dental disease, oral hygiene and typeof dental procedure on bacteremia. It is assumedthat a relationship exists between poor oralhygiene; the extent of dental and periodontal dis-ease; the type of dental procedure; and the fre-quency, nature, magnitude and duration of bac-teremia, but the presumed relationship iscontroversial.24,30,31,39,46,55-62 Nevertheless, availableevidence supports an emphasis on maintaininggood oral hygiene and eradicating dental diseaseto decrease the frequency of bacteremia from rou-tine daily activities.46,57-59,63,64 In patients with poororal hygiene, the frequency of positive blood cul-tures just before dental extraction may be similarto that after extraction.63,64

More than 80 years ago, it was suggested thatpoor oral hygiene and dental disease were moreimportant as a cause of IE than were dental pro-cedures.65 Most studies since that time havefocused instead on the risks of bacteremia asso-ciated with dental procedures. For example, tooth extraction is thought to be the dental procedure most likely to cause bacteremia, with an incidence ranging from 10 to 100percent.24,25,28,30,46,49,53,55,58,66-68 However, numerousother dental procedures have been reported to be associated with risks of bacteremia that are similar to that resulting from tooth extrac-tion.28,29,48,52,55,57,59,69-72 A precise determination of therelative risk of bacteremia resulting from a spe-cific dental procedure in patients with or withoutdental disease probably is not possible.28,73,74

Bleeding often occurs during a dental pro-cedure in patients with or without periodontaldisease. Previous AHA guidelines recommendedantibiotic prophylaxis for dental procedures for

JADA, Vol. 139 http://jada.ada.org January 2008 11SCopyright ©2008 American Dental Association. All rights reserved.

which bleeding was anticipated but not for pro-cedures for which bleeding was not anticipated.1

However, no data show that visible bleedingduring a dental procedure is a reliable predictorfor bacteremia.63 These ambiguities in the pre-vious AHA guidelines led to further uncertaintiesamong health care providers about which dentalprocedures should be covered by prophylaxis.

These factors complicated recommendations inprevious AHA guidelines on prevention of IE,which suggested antibiotic prophylaxis for somedental procedures but not for others. The collec-tive published data suggest that the vast majorityof dental office visits result in some degree of bac-teremia; however, there is no evidence-basedmethod to decide which procedures should requireprophylaxis because no data show that the inci-dence, magnitude or duration ofbacteremia from any dental pro-cedure increases the risk of IE.Accordingly, it is not clear whichdental procedures are more or lesslikely to cause a transient bac-teremia or result in a greater mag-nitude of bacteremia than thatwhich results from routine dailyactivities such as chewing food,tooth brushing or flossing.

In patients with underlying car-diac conditions, lifelong antibiotictherapy is not recommended to pre-vent IE that might result from bac-teremias associated with routine daily activities.5

In patients with dental disease, the focus on thefrequency of bacteremia associated with a specificdental procedure and the AHA guidelines for pre-vention of IE have resulted in an overemphasison antibiotic prophylaxis and an underemphasison maintenance of good oral hygiene and access toroutine dental care, which are likely more impor-tant in reducing the lifetime risk of IE than is theadministration of antibiotic prophylaxis for adental procedure. However, there are no observa-tional or controlled studies to support this contention.

Impact of antibiotic therapy on bacteremia froma dental procedure. The ability of antibiotictherapy to prevent or reduce the frequency, mag-nitude or duration of bacteremia associated with adental procedure is controversial.25,75 Some studiesreported that antibiotics administered before adental procedure reduced the frequency, nature orduration of bacteremia,54,76,77 while others did

not.25,67,78,79 Recent studies suggest that amoxicillintherapy has a statistically significant impact onreducing the incidence, nature and duration ofbacteremia from dental procedures, but it does noteliminate bacteremia.53,54,77 However, no data showthat such a reduction as a result of amoxicillintherapy reduces the risk of or prevents IE. Halland colleagues79 reported that neither penicillin Vnor amoxicillin therapy was effective in reducingthe frequency of bacteremia compared withuntreated control subjects. In patients who under-went a dental extraction, penicillin or ampicillintherapy compared with placebo diminished thepercentage of viridans group streptococci andanaerobes in culture, but there was no significantdifference in the percentage of patients with posi-tive cultures 10 minutes after tooth extraction.25,67

In a separate study, Hall and col-leagues78 reported that patientstreated with cefaclor did not have areduction of postprocedure bac-teremia compared with untreatedcontrol subjects. Contradictory pub-lished results from two studiesshowed reduction of postprocedurebacteremia by erythromycin inone76 but lack of efficacy for erythro-mycin or clindamycin in another.79

Finally, results are contradictoryregarding the efficacy of the use oftopical antiseptics in reducing thefrequency of bacteremia associated

with dental procedures, but the preponderance ofevidence suggests that there is no clear benefit.One study reported that chlorhexidine and povi-done-iodine mouthrinse were effective,80 whileothers showed no statistically significant ben-efit.53,81 Topical antiseptic rinses do not penetratebeyond 3 mm into the periodontal pocket and,therefore, do not reach areas of ulcerated tissuewhere bacteria most often gain entrance to the cir-culation. On the basis of these data, it is unlikelythat topical antiseptics are effective to signifi-cantly reduce the frequency, magnitude and dura-tion of bacteremia associated with a dentalprocedure.

Cumulative risk over time of physiolog-ical bacteremias from routine daily activi-ties compared with the bacteremia from adental procedure. Guntheroth82 estimated acumulative exposure of 5,370 minutes of bac-teremia over a one-month period in dentulouspatients resulting from random bacteremia from


The ability of antibiotic therapy toprevent or reduce thefrequency, magnitude

or duration of bacteremia associated

with a dental procedure is controversial.


chewing food and from oral hygiene measures,such as tooth brushing and flossing, and com-pared that to a duration of bacteremia lasting sixto 30 minutes associated with a single toothextraction. Roberts63 estimated that toothbrushing two times daily for one year had a154,000 times greater risk of exposure to bac-teremia than that resulting from a single toothextraction. The cumulative exposure during oneyear to bacteremia from routine, daily activitiesmay be as high as 5.6 million times greater thanthat resulting from a single tooth extraction, thedental procedure reported to be most likely tocause a bacteremia.63

Data exist for the duration of bacteremia froma single tooth extraction, and it is possible to esti-mate the annual cumulative exposure from dentalprocedures for the average patient. However, cal-culations for the incidence, nature and duration ofbacteremia from routine daily activities are atbest rough estimates, and it is, therefore, not pos-sible to compare precisely the cumulativemonthly or annual duration of exposure for bac-teremia from dental procedures compared withroutine daily activities. Nevertheless, even if theestimates of bacteremia from routine daily activi-ties are off by a factor of 1,000, it is likely that thefrequency and cumulative duration of exposure tobacteremia from routine daily events over oneyear are much higher than those resulting fromdental procedures.

Results of clinical studies of IE prophy-laxis for dental procedures. There are noprospective randomized placebo-controlled studieson the efficacy of antibiotic prophylaxis to preventIE in patients who undergo a dental procedure.Data from published retrospective or prospectivecase-control studies are limited by the followingfactors: (1) the low incidence of IE, which requiresa large number of patients per cohort for statis-tical significance; (2) the wide variation in thetypes and severity of underlying cardiac condi-tions, which would require a large number ofpatients with specific matched control subjects foreach cardiac condition; and (3) the large variety ofinvasive dental procedures and dental diseasestates, which would be difficult to standardize forcontrol groups. These and other limitations com-plicate the interpretation of the results of pub-lished studies of the efficacy of IE prophylaxis inpatients who undergo dental procedures.

Although some retrospective studies suggestedthat there was a benefit from prophylaxis, these

studies were small and reported insufficient clin-ical data. Furthermore, in a number of cases, the incubation period between the dental procedure and the onset of symptoms of IE was prolonged.81,83-85

van der Meer and colleagues86 published astudy of dental procedures in the Netherlandsand the efficacy of antibiotic prophylaxis to pre-vent IE in patients with native or prosthetic car-diac valves. They concluded that dental or otherprocedures probably caused only a small fractionof cases of IE and that prophylaxis would preventonly a small number of cases even if it were 100percent effective. van der Meer and colleagues87

performed a two-year case-control study. Amongpatients for whom prophylaxis was recommended,five of 20 cases of IE occurred despite receivingantibiotic prophylaxis. They concluded that pro-phylaxis was not effective. In a separate study,van der Meer and colleagues88 reported that therewas poor awareness of recommendations for pro-phylaxis among both patients and health careproviders.

Strom and colleagues2 evaluated dental pro-phylaxis and cardiac risk factors in a multicentercase-control study. These authors reported thatMVP, congenital heart disease (CHD), rheumaticheart disease (RHD) and previous cardiac valvesurgery were risk factors for the development ofIE. In this study, control subjects without IE weremore likely to have undergone a dental procedurethan patients with IE (P = .03). The authors con-cluded that dental treatment was not a risk factorfor IE even in patients with valvular heart dis-ease and that few cases of IE could be preventedwith prophylaxis even if it were 100 percent effective.

The studies are in agreement with a recentlypublished French study of the estimated risk ofIE in adults with predisposing cardiac conditionswho underwent dental procedures with or withoutantibiotic prophylaxis.89 These authors concludedthat a “huge number of prophylaxis doses wouldbe necessary to prevent a very low number of IEcases.”

Absolute risk of IE resulting from a dentalprocedure. No published data accurately deter-mine the absolute risk of IE resulting from adental procedure. One study reported that 10 to20 percent of patients with IE caused by oral floraunderwent a preceding dental procedure (within30 or 180 days of onset).86 The evidence linkingbacteremia associated with a dental procedure


with IE is largely circumstantial, and the numberof cases related to a dental procedure is overesti-mated for a number of reasons. For 60 years,noted opinion leaders in medicine suggested alink between bacteremia-causing dental pro-cedures and IE,24 and for 50 years the AHA pub-lished regularly updated guidelines that empha-sized the association between dental proceduresand IE and recommended antibiotic prophylaxis.1

Additionally, bacteremia-producing dental pro-cedures are common; it is estimated that at least50 percent of the population in the United Statesvisits a dentist at least once a year. Furthermore,there are numerous poorly documented casereports that implicate dental procedures asso-ciated with the development of IE, but thesereports did not prove a direct causal relationship.Even in the event of a close tem-poral relationship between adental procedure and IE, it is notpossible to determine with cer-tainty whether the bacteremia thatcaused IE originated from a dentalprocedure or from a randomlyoccurring bacteremia as a result ofroutine daily activities during thesame period. Many case reportsand reviews have included caseswith a remote preceding dentalprocedure, often three to sixmonths before the diagnosis of IE.Studies suggest that the time frame between bac-teremia and the onset of symptoms of IE is usu-ally seven to 14 days for viridans group strepto-cocci or enterococci. Reportedly, 78 percent ofsuch cases of IE occur within seven days of bac-teremia and 85 percent within 14 days.90

Although the upper time limit is not known, it islikely that many cases of IE with incubationperiods longer than two weeks after a dental pro-cedure were attributed incorrectly to the pro-cedure. These and other factors have led to aheightened awareness among patients and healthcare providers of the possible association withdental procedures and IE, which likely has led tosubstantial overreporting of cases attributable todental procedures.

Although the absolute risk for IE from a dentalprocedure is impossible to measure precisely, thebest available estimates are as follows: if dentaltreatment causes 1 percent of all cases of viridansgroup streptococcal IE annually in the UnitedStates, the overall risk in the general population

is estimated to be as low as one case of IE per 14million dental procedures.42,91,92 The estimatedabsolute risk rates for IE from a dental procedurein patients with underlying cardiac conditions areMVP, one per 1.1 million procedures; CHD, oneper 475,000; RHD, one per 142,000; presence of aprosthetic cardiac valve, one per 114,000; andprevious IE, one per 95,000 dental procedures.42,92

Although these calculations of risk are estimates,it is likely that the number of cases of IE thatresults from a dental procedure is exceedinglysmall. Therefore, the number of cases that couldbe prevented by antibiotic prophylaxis, even if100 percent effective, is similarly small. Onewould not expect antibiotic prophylaxis to be near100 percent effective, however, because of thenature of the organisms and choice of antibiotics.

Risk of adverse reactions andcost-effectiveness of prophy-lactic therapy. Nonfatal adversereactions, such as rash, diarrheaand GI upset, occur commonly withuse of the antimicrobials; however,only single-dose therapy is recom-mended for dental prophylaxis, andthese common adverse reactions areusually not severe and are self-lim-ited. Fatal anaphylactic reactionswere estimated to occur in 15 to 25patients per 1 million patients whoreceive a dose of penicillin.93,94

Among patients with a prior penicillin use, 36percent of fatalities from anaphylaxis occurred inthose with a known allergy to penicillin, com-pared with 64 percent of fatalities among thosewith no history of penicillin allergy.95 These cal-culations are at best rough estimates of, and mayoverestimate, the true risk of death caused byfatal anaphylaxis from administration of a peni-cillin. They are based on retrospective reviews orsurveys of patients or on health care providers’recall of events. A prospective study is necessaryto accurately determine the risk of fatal anaphy-laxis resulting from administration of a penicillin.

For 50 years, the AHA has recommended apenicillin as the preferred choice for dental pro-phylaxis for IE. During these 50 years, the Com-mittee is unaware of any cases reported to theAHA of fatal anaphylaxis resulting from theadministration of a penicillin recommended in theAHA guidelines for IE prophylaxis. The Com-mittee believes that a single dose of amoxicillin or


Only an extremelysmall number of cases of infective

endocarditis might be prevented by

antibiotic prophylaxiseven if it were 100percent effective.


ampicillin is safe and is the preferred prophy-lactic agent for patients who do not have a historyof type I hypersensitivity reaction to a penicillin,such as anaphylaxis, urticaria or angioedema.Fatal anaphylaxis from a cephalosporin is esti-mated to be less common than from penicillin andis estimated to be approximately one case per 1million patients.96 Fatal reactions to a single doseof a macrolide or clindamycin are extremelyrare.97,98 There has been only one case report ofdocumented Clostridium difficile colitis after asingle dose of prophylactic clindamycin.99

Summary. Although it has long been assumedthat dental procedures may cause IE in patientswith underlying cardiac risk factors and thatantibiotic prophylaxis is effective, scientific proofis lacking to support these assumptions. The col-lective published evidence suggests that of thetotal number of cases of IE that occur annually, itis likely that an exceedingly small number ofthese cases is caused by bacteremia-producingdental procedures. Accordingly, only an extremelysmall number of cases of IE might be preventedby antibiotic prophylaxis even if it were 100 per-cent effective. The vast majority of cases of IEcaused by oral microflora most likely result fromrandom bacteremias caused by routine dailyactivities, such as chewing food, tooth brushing,flossing, use of toothpicks, use of water irrigationdevices and other activities. The presence ofdental disease may increase the risk of bac-teremia associated with these routine activities.There should be a shift in emphasis away from afocus on a dental procedure and antibiotic prophy-laxis toward a greater emphasis on improvedaccess to dental care and oral health in patientswith underlying cardiac conditions associatedwith the highest risk of adverse outcome from IEand those conditions that predispose to the acquisition of IE.

CARDIAC CONDITIONS AND ENDOCARDITIS

Previous AHA guidelines categorized underlyingcardiac conditions associated with the risk of IE asthose with high risk, moderate risk and negligiblerisk and recommended prophylaxis for patients inthe high- and moderate-risk categories.1 For thepresent guidelines on prevention of IE, the Com-mittee considered three distinct issues: (1) Whatunderlying cardiac conditions over a lifetime havethe highest predisposition to the acquisition ofendocarditis? (2) What underlying cardiac condi-tions are associated with the highest risk of

adverse outcome from endocarditis? (3) Should rec-ommendations for IE prophylaxis be based oneither or both of these two conditions?

Underlying conditions over a lifetime thathave the highest predisposition to the acqui-sition of endocarditis. In Olmsted County,Minn., the incidence of IE in adults ranged fromfive to seven cases per 100,000 person-years.100

This incidence has remained stable during thepast four decades and is similar to that reportedin other studies.101-104 Previously, RHD was themost common underlying condition predisposingto endocarditis, and RHD is still common indeveloping countries.100 In developed countries,the frequency of RHD has declined, and MVP isthe most common underlying condition inpatients with endocarditis.105

Few published data quantitate the lifetimerisk of acquisition of IE associated with a specificunderlying cardiac condition. Steckelberg andWilson91 reported the lifetime risk of acquisitionof IE, which ranged from five per 100,000patient-years in the general population with noknown cardiac conditions to 2,160 per 100,000patient-years in patients who underwent replace-ment of an infected prosthetic cardiac valve. Inthat study, the risk of IE per 100,000 patient-years was 4.6 in patients with MVP without anaudible cardiac murmur and was 52 in patientswith MVP with an audible murmur of mitralregurgitation. Per 100,000 patient-years, the life-time risk (380-440) for RHD was similar to that(308-383) for patients with a mechanical or bio-prosthetic cardiac valve. The highest lifetimerisks per 100,000 patient-years were as follows:cardiac valve replacement surgery for nativevalve IE, 630; previous IE, 740; and prostheticvalve replacement done in patients with pros-thetic valve endocarditis (PVE), 2,160. In a sepa-rate study, the risk of IE per 100,000 patient-years was 271 in patients with congenital aorticstenosis and was 145 in patients with ventricularseptal defect.106 In that study, the risk of IEbefore closure of ventricular septal defect wasmore than twice that after closure. Althoughthese data provide useful ranges of risk in largepopulations, it is difficult to use them to defineaccurately the lifetime risk of acquisition of IE inan individual patient with a specific underlyingcardiac risk factor. This difficulty is based in parton the fact that each cardiac condition, such asRHD or MVP, represents a broad spectrum ofpathology from minimal to severe, and the risk of


IE would likely be influenced by the severity ofvalvular disease.

CHD is another underlying condition with mul-tiple different cardiac abnormalities that rangefrom relatively minor to severe complex cyanoticheart disease. During the past 25 years, there hasbeen an increasing use of various different intra-cardiac valvular prostheses and intravascularshunts, grafts and other devices for repair ofvalvular heart disease and CHD. The diversityand nature of these prostheses and procedureslikely present different levels of risk for acquisi-tion of IE. These factors complicate an accurateassessment of the true lifetime risk of acquisitionof IE in patients with a specific underlying cardiac condition.

On the basis of data from Steckelberg andWilson91 and Strom and colleagues,2

it is clear that the underlying condi-tions discussed above represent alifetime increased risk of acquisitionof IE compared with patients withno known underlying cardiac condi-tion. Accordingly, when using pre-vious AHA guidelines in the deci-sion to recommend IE prophylaxisfor a patient scheduled to undergo adental, GI or GU tract procedure,health care providers were requiredto base their decision on population-based studies of risk of acquisitionof IE that may or may not be rel-evant to their specific patient. Fur-thermore, practitioners had toweigh the potential efficacy of IEprophylaxis in a patient who may neither neednor benefit from such therapy against the risk ofadverse reaction to the antibiotic prescribed.Finally, health care providers had to consider thepotential medicolegal risk of not prescribing IEprophylaxis. For dental procedures, there is agrowing body of evidence that suggests that IEprophylaxis may prevent only an exceedinglysmall number of cases of IE, as discussed in detail above.

Cardiac conditions associated with thehighest risk of adverse outcome from endo-carditis. Endocarditis, irrespective of the under-lying cardiac condition, is a serious, life-threatening disease that was always fatal in thepreantibiotic era. Advances in antimicrobialtherapy, early recognition and management ofcomplications of IE, and improved surgical tech-

nology have reduced the morbidity and mortalityof IE. Numerous comorbid factors, such as olderage, diabetes mellitus, immunosuppressive condi-tions or therapy, and dialysis, may complicate IE.Each of these comorbid conditions independentlyincreases the risk of adverse outcome from IE,and they often occur in combination, which fur-ther increases morbidity and mortality. Addition-ally, there may be long-term consequences of IE.Over time, the cardiac valve damaged by IE mayundergo progressive functional deterioration that may result in the need for cardiac valvereplacement.

In native valve viridans group streptococcal orenterococcal IE, the spectrum of disease mayrange from a relatively benign infection to severevalvular dysfunction, dehiscence, congestive heart

failure, multiple embolic eventsand death; however, the underlyingconditions shown in Box 3 virtuallyalways have an increased risk ofadverse outcome. For example,patients with viridans group strep-tococcal PVE have a mortality ofapproximately 20 percent orgreater,107-110 whereas the mortalityfor patients with viridans groupstreptococcal native valve IE is 5percent or less.109,111-117 Similarly,the mortality of enterococcal PVE ishigher than that of native valveenterococcal IE.108,109,115,118 Moreover,patients with PVE are more likelythan those with native valve endo-carditis to develop heart failure,

the need for cardiac valve replacement surgery,perivalvular extension of infection and othercomplications.

Patients with relapsing or recurrent IE are atgreater risk of congestive heart failure andincreased need for cardiac valve replacementsurgery, and they have a higher mortality than do patients with a first episode of native valveIE.119-125 Additionally, patients with multipleepisodes of native or prosthetic valve IE are atgreater risk of additional episodes of endocarditis,each of which is associated with the risk of moreserious complications.91

Published series regarding endocarditis inpatients with CHD are underpowered to deter-mine the extent to which a specific form of CHDis an independent risk factor for morbidity andmortality. Nevertheless, most retrospective case


There should be ashift toward a greateremphasis on improvedaccess to dental care

and oral health in patients with

underlying cardiacconditions associatedwith the highest riskof adverse outcome

from infective endocarditis.


series suggest thatpatients with complexcyanotic heart disease andthose who have postopera-tive palliative shunts, con-duits or other prostheseshave a high lifetime risk ofacquiring IE, and thesesame groups appear athighest risk for morbidityand mortality among allpatients with CHD.126-130 Inaddition, multiple seriesand reviews reported thatthe presence of prostheticmaterial131,132 and complexcyanotic heart disease inpatients of very young age(newborns and infants younger than 2 years)133,134

are two factors associated with the worst prog-noses from IE. Some types of CHD may berepaired completely without residual cardiacdefects. In Box 3, the Committee concludes thatprophylaxis is reasonable for dental proceduresfor these patients during the first six monthsafter the procedure. In these patients, endothe-lialization of prosthetic material or devices occurswithin six months after the procedure.135 TheCommittee does not recommend prophylaxis fordental procedures more than six months after theprocedure provided that there is no residualdefect from the repair. In most instances, treat-ment of patients who have infected prostheticmaterials requires surgical removal in addition tomedical therapy with associated high morbidityand mortality rates.

Should IE prophylaxis be recommendedfor patients with the highest risk of acquisi-tion of IE or for patients with the highestrisk of adverse outcome from IE? In a majordeparture from previous AHA guidelines, theCommittee no longer recommends IE prophylaxisbased solely on an increased lifetime risk ofacquisition of IE. It is noteworthy that patientswith the conditions listed in Box 3 with a pros-thetic cardiac valve, those with a previous episodeof IE and some patients with CHD are alsoamong those patients with the highest lifetimerisk of acquisition of endocarditis. No publisheddata demonstrate convincingly that the adminis-tration of prophylactic antibiotics prevents IEassociated with bacteremia from an invasive pro-cedure. We cannot exclude the possibility that

there may be an exceedingly small number ofcases of IE that could be prevented by prophy-lactic antibiotics in patients who undergo an inva-sive procedure. However, if prophylaxis is effec-tive, such therapy should be restricted to thosepatients with the highest risk of adverse outcomefrom IE who would derive the greatest benefitfrom prevention of IE. In patients with under-lying cardiac conditions associated with thehighest risk of adverse outcome from IE (Box 3),IE prophylaxis for dental procedures is reason-able, even though we acknowledge that its effec-tiveness is unknown (Class IIb, LOE B).

Compared with previous AHA guidelines,under these revised guidelines, many fewerpatients would be candidates to receive IE pro-phylaxis. We believe these revised guidelines arein the best interest of the patients and healthcare providers and are based on the best availablepublished data and expert opinion. Additionally,the change in emphasis to restrict prophylaxis toonly those patients with the highest risk ofadverse outcome should reduce the uncertaintiesamong patients and providers about who shouldreceive prophylaxis. MVP is the most commonunderlying condition that predisposes to acquisi-tion of IE in the Western world; however, theabsolute incidence of endocarditis is extremelylow for the entire population with MVP, and it isnot usually associated with the grave outcomeassociated with the conditions identified in Box 3.Thus, IE prophylaxis is no longer recommendedin this group of patients.

Finally, the administration of prophylacticantibiotics is not risk-free as discussed above.


Cardiac conditions associated with the highest risk of adverse outcome from endocarditis for which prophylaxis with dental procedures is reasonable.

dProsthetic cardiac valve or prosthetic material used for cardiac valve repairdPrevious infective endocarditisdCongenital heart disease (CHD)*

dUnrepaired cyanotic CHD, including palliative shunts and conduitsdCompletely repaired congenital heart defect with prosthetic material or

device, whether placed by surgery or by catheter intervention, during the firstsix months after the procedure†

dRepaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibit endothelialization)

dCardiac transplantation recipients who develop cardiac valvulopathy

* Except for the conditions listed above, antibiotic prophylaxis is no longer recommended for any other formof CHD.

† Prophylaxis is reasonable because endothelialization of prosthetic material occurs within six months afterthe procedure.

BOX 3


Additionally, the widespread use of antibiotictherapy promotes the emergence of resistantmicroorganisms most likely to cause endocarditis,such as viridans group streptococci and entero-cocci. The frequency of multidrug-resistant viri-dans group streptococci and enterococci hasincreased dramatically during the past twodecades. This increased resistance has reducedthe efficacy and number of antibiotics availablefor the treatment of IE.

ANTIBIOTIC REGIMENS

General principles. An antibiotic for prophy-laxis should be administered in a single dosebefore the procedure. If the dosage of antibiotic isinadvertently not administered before the pro-cedure, the dosage may be administered up to twohours after the procedure. However, administra-tion of the dosage after the procedure should beconsidered only when the patient did not receivethe preprocedural dose. Some patients who arescheduled for an invasive procedure may have acoincidental endocarditis. The presence of fever orother manifestations of systemic infection shouldalert the provider to the possibility of IE. In thesecircumstances, it is important to obtain blood cul-tures and other relevant tests before administra-tion of antibiotics intended to prevent IE. Failureto do so may result in delay in diagnosis or treat-ment of a concomitant case of IE.

Regimens for dental procedures. PreviousAHA guidelines on prophylaxis listed a substan-tial number of dental procedures and events forwhich antibiotic prophylaxis was recommendedand those procedures for which prophylaxis wasnot recommended. On the basis of a criticalreview of the published data, it is clear that tran-sient viridans group streptococcal bacteremia

may result from any dental procedure thatinvolves manipulation of the gingival or peri-apical region of teeth or perforation of the oralmucosa. It cannot be assumed that manipulationof a healthy-appearing mouth or a minimallyinvasive dental procedure reduces the likelihoodof a bacteremia. Therefore, antibiotic prophylaxisis reasonable for patients with the conditionslisted in Box 3 who undergo any dental procedurethat involves the gingival tissues or periapicalregion of a tooth and for those procedures thatperforate the oral mucosa (Box 4). Although IEprophylaxis is reasonable for these patients, itseffectiveness is unknown (Class IIa, LOE C).This includes procedures such as biopsies, sutureremoval and placement of orthodontic bands, butdoes not include routine anesthetic injectionsthrough noninfected tissue, taking dental radi-ographs, placement of removable prosthodonticor orthodontic appliances, placement of ortho-dontic brackets or adjustment of orthodonticappliances. Finally, there are other events thatare not dental procedures and for which prophy-laxis is not recommended, such as shedding ofprimary teeth and trauma to the lips and oralmucosa.

In this limited patient population, prophylacticantimicrobial therapy should be directed againstviridans group streptococci. During the past twodecades, there has been a significant increase inthe percentage of strains of viridans group strep-tococci resistant to antibiotics recommended inprevious AHA guidelines for the prevention of IE.Prabhu and colleagues136 studied susceptibilitypatterns of viridans group streptococci recoveredfrom patients with IE diagnosed during a periodfrom 1971 to 1986 and compared these suscepti-bilities with those of viridans group streptococcifrom patients with IE diagnosed from 1994 to2002. In this study, none of the strains of viridansgroup streptococci were penicillin-resistant in theearly period, compared with 13 percent of strainsthat were intermediate or fully penicillin-resistant during the later period. In this study,macrolide resistance increased from 11 to 26 per-cent and clindamycin resistance from 0 to 4percent.

Among 352 blood culture isolates of viridansgroup streptococci, resistance rates were 13 per-cent for penicillin, 15 percent for amoxicillin, 17percent for ceftriaxone, 38 percent for erythro-mycin and 96 percent for cephalexin.137 The rankorder of decreasing level of activity of cephalo-


Dental procedures for which endocarditis prophylaxis is reasonable for patients in Box 3.

All dental procedures that involve manipulation ofgingival tissue or the periapical region of teeth orperforation of the oral mucosa.*

* The following procedures and events do not need prophylaxis: routineanesthetic injections through noninfected tissue, taking dental radi-ographs, placement of removable prosthodontic or orthodontic appli-ances, adjustment of orthodontic appliances, placement of orthodonticbrackets, shedding of primary teeth, and bleeding from trauma to thelips or oral mucosa.

BOX 4


sporins in that study was cefpodoxime equal toceftriaxone, greater than cefprozil, equal tocefuroxime, and cephalexin was the least active.In other studies, resistance of viridans groupstreptococci to penicillin ranged from 17 to 50 per-cent138-143 and resistance to ceftriaxone from 22 to42 percent.132,141 Ceftriaxone was two to four timesmore active in vitro than was cefazolin.132,141 Simi-larly high rates of resistance were reported formacrolides, ranging from 22 to 58 per-cent138,142,144,145; resistance to clindamycin rangedfrom 13 to 27 percent.129,130,132,138,139,141

Most of the strains of viridans group strepto-cocci in the above-cited studies were recoveredfrom patients with serious underlying illnesses,including malignancies and febrile neutropenia.These patients are at increased risk of infectionand colonization by multiple drug-resistantmicroorganisms, including viridans group strepto-cocci. Accordingly, these strains may not be repre-sentative of susceptibility patterns of viridansgroup streptococci recovered from presumablynormal patients who undergo a dental procedure.Diekema and colleagues138 reported that 32 per-cent of strains of viridans group streptococci wereresistant to penicillin in patients without cancer.King and colleagues145 reported erythromycinresistance in 41 percent of streptococci recoveredfrom throat cultures in otherwise healthypatients who presented with mild respiratorytract infections. In that study, after treatmentwith either azithromycin or clindamycin, the per-centage of resistant streptococci increased to 82percent and 71 percent, respectively. Accordingly,the resistance rates of viridans group streptococciare similarly high in otherwise healthy patientsor in patients with serious underlying diseases.

The impact of viridans group streptococcalresistance on antibiotic prevention of IE isunknown. If resistance in vitro is predictive oflack of clinical efficacy, the high resistance ratesof viridans group streptococci provide additionalsupport for the assertion that prophylactictherapy for a dental procedure is of little, if any,value. It is impractical to recommend prophylaxiswith only those antibiotics, such as vancomycin ora fluoroquinolone, that are highly active in vitroagainst viridans group streptococci. There is noevidence that such therapy is effective for prophy-laxis of IE, and their use might result in thedevelopment of resistance of viridans group strep-tococci and other microorganisms to these andother antibiotics.

In Table 2, amoxicillin is the preferred choicefor oral therapy because it is well-absorbed in theGI tract and provides high and sustained serumconcentrations. For patients who are allergic topenicillins or amoxicillin, the use of cephalexin oranother first-generation oral cephalosporin, clin-damycin, azithromycin or clarithromycin is rec-ommended. Even though cephalexin was lessactive against viridans group streptococci thanother first-generation oral cephalosporins in onestudy,137 cephalexin is included in Table 2. Nodata show superiority of one oral cephalosporinover another for prevention of IE, and genericcephalexin is widely available and is relativelyinexpensive. Because of possible cross-reactions, acephalosporin should not be administered topatients with a history of anaphylaxis, angio-edema or urticaria after treatment with any formof penicillin, including ampicillin or amoxicillin.Patients who are unable to tolerate an oral antibi-otic may be treated with ampicillin, ceftriaxone orcefazolin administered intramuscularly or intra-venously. For patients who are allergic to ampi-cillin and are unable to tolerate an oral agent,therapy is recommended with parenteral cefa-zolin, ceftriaxone or clindamycin.

A summary of the major changes in theseupdated recommendations for prevention of IEcompared with previous AHA recommendations isshown in Box 5.

SPECIFIC SITUATIONS AND CIRCUMSTANCES

Patients already receiving antibiotics. If apatient is already receiving chronic antibiotictherapy with an antibiotic that is also recom-mended for IE prophylaxis for a dental procedure,it is prudent to select an antibiotic from a dif-ferent class rather than to increase the dosage ofthe current antibiotic. For example, antibioticregimens used to prevent the recurrence of acuterheumatic fever are administered in dosageslower than those recommended for the preventionof IE. Patients who take an oral penicillin for sec-ondary prevention of rheumatic fever or for otherpurposes are likely to have viridans group strep-tococci in their oral cavity that are relativelyresistant to penicillin or amoxicillin. In suchcases, the provider should select either clin-damycin, azithromycin or clarithromycin for IEprophylaxis for a dental procedure, but only forpatients shown in Box 3. Because of possiblecross-resistance of viridans group streptococci


with cephalosporins, this class ofantibiotics should be avoided. If pos-sible, it would be preferable to delay adental procedure until at least 10 daysafter completion of the antibiotictherapy. This may allow time for theusual oral flora to be re-established.

Patients receiving parenteral antibi-otic therapy for IE may require dentalprocedures during antimicrobialtherapy, particularly if subsequent car-diac valve replacement surgery is antici-pated. In these cases, the parenteralantibiotic therapy for IE should be con-tinued and the timing of the dosageadjusted to be administered 30 to 60minutes before the dental procedure.This parenteral antimicrobial therapy isadministered in such high doses thatthe high concentration would overcomeany possible low-level resistance devel-oped among mouth flora (unlike the con-centration that would occur after oraladministration).

Patients who receiveanticoagulants. Intra-muscular injections for IEprophylaxis should beavoided in patients whoare receiving anticoagu-lant therapy (Class I, LOEA). In these circum-stances, orally adminis-tered regimens should begiven whenever possible.Intravenously adminis-tered antibiotics should beused for patients who areunable to tolerate orabsorb oral medications.

Patients who undergocardiac surgery. Acareful dental evaluation isrecommended so thatrequired dental treatmentmay be completed when-ever possible before cardiacvalve surgery or replace-ment or repair of CHD.Such measures maydecrease the incidence oflate PVE caused by viri-dans group streptococci.


TABLE 2

Regimens for a dental procedure.SITUATION AGENT REGIMEN: SINGLE DOSE 30-60

MINUTES BEFORE PROCEDURE

Adults Children

* IM: Intramuscular.† IV: Intravenous.‡ Or other first- or second-generation oral cephalosporin in equivalent adult or pediatric

dosage.§ Cephalosporins should not be used in a person with a history of anaphylaxis, angioedema

or urticaria with penicillins or ampicillin.

Oral

Unable to Take OralMedication

Allergic to Penicillins or AmpicillinOral

Allergic to Penicillins or Ampicillin andUnable to Take Oral Medication

2 grams

2 g IM* or IV†

1 g IM or IV

2 g

600 mg

500 mg

1 g IM or IV

600 mg IM orIV

Amoxicillin

AmpicillinOR

Cefazolin or ceftriaxone

Cephalexin‡§

ORClindamycin

ORAzithromycin orclarithromycin

Cefazolin or ceftriaxone§

ORClindamycin

50 milligramsper kilogram

50 mg/kg IMor IV

50 mg/kg IMor IV

50 mg/kg

20 mg/kg

15 mg/kg

50 mg/kg IMor IV

20 mg/kg IMor IV

Summary of major changes in updated document.

dWe concluded that bacteremia resulting from daily activities is much morelikely to cause infective endocarditis (IE) than bacteremia associated with adental procedure.

dWe concluded that only an extremely small number of cases of IE might be pre-vented by antibiotic prophylaxis even if prophylaxis is 100 percent effective.

dAntibiotic prophylaxis is not recommended based solely on an increased life-time risk of acquisition of IE.

dLimit recommendations for IE prophylaxis only to those conditions listed in Box 3.

dAntibiotic prophylaxis is no longer recommended for any other form of congen-ital heart disease, except for the conditions listed in Box 3.

dAntibiotic prophylaxis is reasonable for all dental procedures that involvemanipulation of gingival tissues or periapical region of teeth or perforation oforal mucosa only for patients with underlying cardiac conditions associatedwith the highest risk of adverse outcome from IE (Box 3).

dAntibiotic prophylaxis is reasonable for procedures on respiratory tract orinfected skin, skin structures or musculoskeletal tissue only for patients withunderlying cardiac conditions associated with the highest risk of adverse out-come from IE (Box 3).

dAntibiotic prophylaxis solely to prevent IE is not recommended for gastroin-testinal or genitourinary tract procedures.

dAlthough these guidelines recommend changes in indications for IE prophy-laxis with regard to selected dental procedures (see text), the writing groupreaffirms that those medical procedures listed as not requiring IE prophylaxisin the 1997 statement remain unchanged and extends this view to vaginaldelivery, hysterectomy, and tattooing. Additionally, the writing group advisesagainst body piercing for patients with conditions listed in Box 3 because of thepossibility of bacteremia, while recognizing that there are minimal publisheddata regarding the risk of bacteremia or endocarditis associated with bodypiercing.

BOX 5


OTHER CONSIDERATIONS

There is no evidence that coronary artery bypassgraft surgery is associated with a long-term riskfor infection. Therefore, antibiotic prophylaxisfor dental procedures is not needed for patientswho have undergone this surgery. Antibiotic pro-phylaxis for dental procedures is not recom-mended for patients with coronary artery stents(Class III, LOE C). The treatment and preven-tion of infection for these and other endovasculargrafts and prosthetic devices are addressed in aseparate AHA article.146 There are insufficientdata to support specific recommendations forpatients who have undergone heart transplanta-tion. Such patients are at risk of acquiredvalvular dysfunction, especially during episodesof rejection. Endocarditis that occurs in a hearttransplant patient is associated with a high riskof adverse outcome (Box 3).147 Accordingly, theuse of IE prophylaxis for dental procedures incardiac transplant recipients who develop car-diac valvulopathy is reasonable, but the useful-ness is not well-established (Class IIa, LOE C)(Box 4). The use of prophylactic antibiotics toprevent infection of joint prostheses duringpotentially bacteremia-inducing procedures isnot within the scope of this document.

FUTURE CONSIDERATIONS

Prospective placebo-controlled double-blindedstudies of antibiotic prophylaxis of IE in patientswho undergo a bacteremia-producing procedurewould be necessary to evaluate accurately theefficacy of IE prophylaxis. Additional prospectivecase-control studies are needed. The AHA hasmade substantial revisions to previously pub-lished guidelines on IE prophylaxis. Based onour current recommendations, we anticipatethat significantly fewer patients will receive IEprophylaxis for a dental procedure. Studies arenecessary to monitor the effects, if any, of theserecommended changes in IE prophylaxis. Theincidence of IE could change or stay the same.Because the incidence of IE is low, smallchanges in incidence may take years to detect.Accordingly, we urge that such studies bedesigned and instituted promptly so that anychange in incidence may be detected soonerrather than later. Subsequent revisions of theAHA guidelines on the prevention of IE will bebased on the results of these studies and otherpublished data. ■

The writing group thanks the following international experts oninfective endocarditis for their valuable comments: Drs. ChristaGohlke-Bärwolf, Roger Hall, Jae-Hoon Song, Catherine Kilmartin,Catherine Leport, José M. Miró, Christopher Naber, Graham Robertsand Jan T.M. van der Meer. The writing group also thanks Dr. GeorgeMeyer for his helpful comments regarding gastroenterology. Finally,the writing group would like to thank Lori Hinrichs for her superbassistance with the preparation of this manuscript.

This article was adapted from Wilson W, Taubert KA, Gewitz M, etal. Prevention of Infective Endocarditis: Guidelines From the AmericanHeart Association—A Guideline From the American Heart AssociationRheumatic Fever, Endocarditis and Kawasaki Disease Committee,Council on Cardiovascular Disease in the Young, and the Council onClinical Cardiology, Council on Cardiovascular Surgery and Anes-thesia, and the Quality of Care and Outcomes Research Interdiscipli-nary Working Group. Circulation 2007;116:1736-54. Copyright 2007American Heart Association. All rights reserved. Any reproduction oruse is prohibited without the express permission of the AHA.

Dr. Wilson is a professor of medicine, Mayo Clinic, Rochester, Minn.Dr. Taubert is a senior scientist, American Heart Association, Dallas,

and a professor, University of Texas Southwest Medical School, Dallas.Dr. Gewitz is a professor and the vice chair, Department of Pedi-

atrics, Children’s Hospital of Westchester, New York Medical College,Valhalla.

Dr. Lockhart is the chairman, Department of Oral Medicine, Car-olinas Medical Center, Charlotte, N.C.

Dr. Baddour is a professor of medicine, Mayo Clinic, Rochester, Minn.Dr. Levison is a professor medicine and public health, Drexel Univer-

sity College of Medicine, Philadelphia.Dr. Bolger is a William Watt Kerr professor of clinical medicine, Uni-

versity of California, San Francisco.Dr. Cabell is a professor of medicine, Duke University, Durham, N.C.Dr. Takahashi is a professor of pediatrics, Childrens Hospital Los

Angeles, University of Southern California.Dr. Baltimore is a professor, pediatrics infectious diseases and epi-

demiology/public health, Yale University School of Medicine, NewHaven, Conn.

Dr. Newburger is a professor of pediatrics, Harvard Medical School,Boston, and associate chief for academic affairs, Department of Cardi-ology, Children’s Hospital, Boston.

Dr. Strom is the chair and a professor of biostatistics and epidemi-ology, University of Pennsylvania School of Medicine, Philadelphia.

Dr. Tani is a professor of pediatrics, University of Utah School ofMedicine, Salt Lake City.

Dr. Gerber is a professor of pediatrics, Cincinnati Children’s HospitalMedical Center.

Dr. Bonow is the chief, Division of Cardiology, and a professor ofmedicine, Northwestern Memorial Hospital, Chicago.

Dr. Pallasch is a professor emeritus of dentistry, University ofSouthern California, Los Angeles.

Dr. Shulman is a professor of pediatrics and the chief, infectious dis-eases, Children’s Memorial Hospital, Chicago.

Dr. Rowley is a professor of pediatrics, Children’s Memorial Hospital,Chicago.

Dr. Burns is a professor and the chief, Division of Allergy,Immunology, Department of Pediatrics, University of California, SanDiego.

Dr. Ferrieri is a professor, Department of Laboratory Medicine andPathology, and a professor of pediatrics, University of Minnesota Med-ical School, Minneapolis.

Dr. Gardner is the medical director, Christiana Care Health Systems,Newark, Del.

Dr. Goff is a professor, Public Health Sciences and Internal Medicine,Wake Forest University School of Medicine, Winston-Salem, N.C.

Dr. Durack is senior vice president, Corporate Medical Affairs,Becton, Dickinson and Company, Franklin Lakes, N.J. and the directorof pre-clinical and clinical development, Becton, Dickinson and Com-pany, and a consulting professor of medicine, Duke University,Durham, N.C.

Address reprint requests to Division of Science, American DentalAssociation Council on Scientific Affairs, 211 E. Chicago Ave., Chicago,Ill. 60611, e-mail “[email protected]”.

Readers interested in additional information regarding the authors’conflicts of interest may access it via the Supplemental Data link in theonline version of the article on the JADA Web site (“http://jada.ada.org”).


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