(69621703) circulation-2007-wilson-1736-54

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Prevention of Infective Endocarditis: Guidelines From the American Heart Association: AGuideline From the American Heart Association Rheumatic Fever, Endocarditis, and

Kawasaki Disease ommittee, ouncil on ardiovascular Disease in the !oun", and theouncil on linical ardiolo"#, ouncil on ardiovascular $ur"er# and Anesthesia, andthe %ualit# of are and &utcomes Research Interdisci'linar# (orkin" Grou'

Walter Wilson, Kathryn A. Taubert, Michael Gewitz, Peter B. Lockhart, Larry M. Baddour,Matthew Levison, Ann Boler, !hristo"her #. !abell, Masato Takahashi, $obert %. Balti&ore,'ane W. (ewburer, Brian L. %tro&, Lloyd ). Tani, Michael Gerber, $obert *. Bonow, Tho&as

Pallasch, %tan+ord T. %hul&an, Anne #. $owley, 'ane !. Burns, Patricia errieri, Ti&othyGardner, -avid Go++, -avid T. -urack and The !ouncil on %cienti+ic A++airs o+ the A&erican

-ental Association has a""roved the uideline as it relates to dentistry. n addition, thisuideline has been endorsed by the A&erican Acade&y o+ Pediatrics, n+ectious -iseases

%ociety o+ A&erica, the nternational %ociety o+ !he&othera"y +or n+ection and !ancer, andthe Pediatric n+ectious -iseases %ociety.

Circulation. /001233453164731892 oriinally "ublished online A"ril 3:, /0012doi5 30.3343;!$!<LAT*(A#A.304.3=60:8Circulation is "ublished by the A&erican #eart Association, 1/1/ Greenville Avenue,

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(ilson et al Prevention of Infective Endocarditis 1737

evidence +or "ractice uidelines were used. The "a"er was subseuently reviewed by outside

e"erts not a++iliated with the writin rou" and by the A#A %cience Advisory and !oordinatin

!o&&ittee.

Conclusions FThe &a@or chanes in the u"dated reco&&endations include the +ollowin5 D3E The

!o&&ittee concluded that only an etre&ely s&all nu&ber o+ cases o+ in+ective endocarditis &iht

be "revented by antibiotic "ro"hylais +or dental "rocedures even i+ such "ro"hylactic thera"y were300 e++ective. D/E n+ective endocarditis "ro"hylais +or dental "rocedures is reasonable only +or

"atients with underlyin cardiac conditions associated with the hihest risk o+ adverse outco&e

+ro& in+ective endocarditis. D6E or "atients with these underlyin cardiac conditions, "ro"hylais is

reasonable +or all dental "rocedures that involve &ani"ulation o+ inival tissue or the "eria"ical

reion o+ teeth or "er+oration o+ the oral &ucosa. D9E Pro"hylais is not reco&&ended based solely

on an increased li+eti&e risk o+ acuisition o+ in+ective endocarditis. D8E Ad&inistration o+

antibiotics solely to "revent endocarditis is not reco&&ended +or "atients who undero a

enitourinary or astrointestinal tract "rocedure. These chanes are intended to de+ine &ore clearly

when in+ective endocarditis "ro"hylais is or is not reco&&ended and to "rovide &ore uni+or& and

consistent lobal reco&&endations. 8Circulation+ 9..;--/:-5/<-7=+>Ke# (ords: A#A %cienti+ic %tate&ents cardiovascular diseases

endocarditis "revention antibiotic

"ro"hylais

n+ective endocarditis DE is an unco&&on

but li+e7 threatenin in+ection. -es"ite advancesin dianosis, anti&i7 crobial thera"y, surical

techniues, and &anae&ent o+ co&7 "lications,

"atients with still have hih &orbidity

and &ortality rates related to this condition.

%ince the last A&erican #eart Association

DA#AE "ublication on "revention o+ in

3::1,3 &any authorities and societies, as well as

the conclusions o+ "ublished studies, have

uestioned the e++icacy o+ anti&icro7 bial

"ro"hylais to "revent in "atients who

undero a dental, astrointestinal DGE, or

enitourinary DG<E tract "rocedure and have

suested that the A#A uidelines should be

revised./N8

Me&bers o+ the $heu&atic ever, ndocarditis,

and Kawasaki -isease !o&&ittee o+ the A#A

!ouncil on !ardiovascular -isease in the )oun

Dthe !o&&itteeE and a national and

international rou" o+ e"erts on etensively

reviewed data "ublished on the "revention o+ .

The !o&&ittee is es"ecially rate+ul to a rou"

o+ international e"erts on who "rovided

content review and in"ut on this docu&ent DseeAcknowled7 &entsE. The revised uidelines +or

"ro"hylais are the sub@ect o+ this re"ort.

The writin rou" was chared with the task

o+ "er+or&7 in an assess&ent o+ the evidence

and ivin a classi+ica7 tion o+ reco&&endations

and a level o+ evidence DL*E to each

reco&&endation. The A&erican !ollee o+

!ardiol7 oy DA!!E;A#A classi+ication syste&

was used as +ollows.

lassification of

Recommendations:lass I: !onditions +or which there isevidence and;or eneral aree&ent that a iven "rocedure or treat&ent is bene+icial, use+ul,and e++ective.lass II: !onditions +or which there iscon+lictin evi7 dence and;or a diverence o+o"inion about the use+ulness; e++icacy o+ a "rocedure or treat&ent.

lass IIa: Weiht o+ evidence;o"inion is in+avor o+ use+ulness;e++icacy.

lass II): <se+ulness;e++icacy is less well-ownloaded +ro& htt"5;;[email protected]; by uest on Auust 60, /036






reco&&endations were







1738 Circulation &cto)er 6, 9..

Table 1. Summary of 9 Iterations of AHA-Recommended Antibiotic Regimens From 1955 to 1997 forental!Res"iratoryTract #rocedures$

Year (Reference) Primary Regimens for DentalProcedures

1955 (6) Aqueous penicillin 600 000 and procaine penicillin 600 000 in oil containing !"aluminum monostearate administered #$ %0 minutes &efore t'e operatie procedure

195 () *or ! days &efore surgery+ penicillin !00 000 to !50 000 &y mout' , times per day- .nday of surgery+ penicillin !00 000 to

!50 000 &y mout' , times per day and aqueous penicillin 600 000 /it' procaine penicillin600 000 #$ %0 to 60 minutes &efore surgery- *or ! days after+ !00 000 to !50 000 &y

mout' , times per day-

1960 () tep #2 prop'yla3is ! days &efore surgery /it' procaine penicillin 600 000 #$ on eac'day

tep ##2 day of surgery2 procaine penicillin 600 000 #$ supplemented &y crystallinepenicillin 600 000 #$ 1 'our &efore surgical procedure

tep ###2 for ! days after surgery2 procaine penicillin 600 000 #$ eac' day

1965 (9) Day of procedure2 procaine penicillin 600 000 + supplemented &y crystalline penicillin600 000 #$ 1 to ! 'ours &efore t'e procedure

*or ! days after procedure2 procaine penicillin 600 000 #$ eac' day

19! (10) Procaine penicillin 4 600 000 mi3ed /it' crystalline penicillin 4 !00 000 #$ 1

'our &efore procedure and once daily for t'e ! days after t'e procedure

19 (11) Aqueous crystalline penicillin 4 (1 000 000 #$) mi3ed /it' procaine penicillin 4 (600

000 #$) %0 minutes to 1 'our &efore procedure and t'en penicillin 500 mg orally eery 6'ours for doses-

19, (1!) Penicillin ! g orally 1 'our &efore+ t'en 1 g 6 'ours after initial dose

1990 (1%) Amo3icillin % g orally 1 'our &efore procedure+ t'en 1-5 g 6 'ours after initial dose

199 (1) Amo3icillin ! g orally 1 'our &efore procedure

#$ indicates intramuscularly-

7'ese regimens /ere for adults and represented t'e initial regimen listed in eac' ersion of t'erecommendations- #n some ersions+ 1 regimen /as included-

intended to serve as a uideline, not asestablished standard o+ care. The &ost recent

A#A docu&ent on "ro"hylais was

"ublished in 3::1.3 The 3::1 docu&ent

strati+ied cardiac conditions into hih7,

&oderate7, and low7risk Dneliible riskE

cateories, with "ro"hylais not reco&&ended

+or the low7risk rou".3 An even &ore detailed

list o+ dental, res"i7 ratory, G, and G< tract

"rocedures +or which "ro"hylais was and was

not reco&&ended was "rovided. The 3::1docu&ent was notable +or its

acknowled&ent that &ost cases o+ are not

attributable to an invasive "rocedure but ratherare the result o+ rando&ly occurrin bactere&ias

+ro& routine daily activities and +or its

acknowled&ent o+ "ossi7 ble "ro"hylais

+ailures.

Rationale for Revisin" the -66 Documentt is clear +ro& the above chronoloy that theA#A uidelines

+or "ro"hylais have been in a "rocess o+

evolution &ore than 80 years. The rationale +or

"ro"hylais was based larely on e"ert o"inionand what see&ed to be a rational and "rudent

atte&"t to "revent a li+e7threatenin in+ection.



*n the basis o+ the A!! and A#A Task orce on

Practice Guide7 linesO evidence7based radin

syste& +or rankin reco&&en7 dations, the

reco&&endations in the A#A docu&ents "ub7

lished durin the "ast 80 years would be !lass

b, L* !. Accordinly, the basis +or

reco&&endations +or "ro"hy7 lais was not

well established, and the uality o+ evidence was

li&ited to a +ew case7control studies or was

based on e"ert o"inion, clinical e"erience, and

descri"tive studies that utilized surroate

&easures o+ risk.

*ver the years, other international societies

have "ublished reco&&endations and uidelines

+or the "revention o+ .39,38

$ecently, the British %ociety +or Anti&icrobial

!he&other7 a"y issued new "ro"hylais

reco&&endations.38 This

rou" now reco&&ends "ro"hylais be+ore

dental "rocedures only +or "atients who have a

history o+ "revious or who have had cardiac

valve re"lace&ent or surically constructed

"ul&onary shunts or conduits.

The +unda&ental underlyin "rinci"les that

drove the +or&ulation o+ the A#A uidelines and

the : "revious A#A docu&ents were that D3E

is an unco&&on but li+e7 threatenin disease,

and "revention is "re+erable to treat&ent o+

established in+ection2 D/E certain underlyin

cardiac con7 ditions "redis"ose to 2 D6E

bactere&ia with oranis&s known to cause

occurs co&&only in association with invasive

dental, G, or G< tract "rocedures2 D9E

anti&icrobial "ro"hylais was "roven to be

e++ective +or "revention o+ e"eri&ental in

ani&als2 and D8E anti&icrobial "ro"hylais wasthouht to be e++ective in hu&ans +or "revention

o+ associated with dental, G, or G< tract

"rocedures. The !o&&ittee believes that o+

these 8 underlyin "rinci"les, the +irst 9 are valid

and have not chaned durin the "ast 60 years.

(u&erous "ublications have uestioned the

validity o+ the +i+th "rinci"le and suested

revision o+ the uidelines, "ri&arily +or reasons

as shown in Table /.

Another reason that led the !o&&ittee torevise the 3::1 docu&ent was that over the "ast

80 years, the A#A uide7 lines on "revention o+

beca&e overly co&"licated, &akin it

di++icult +or "atients and healthcare "roviders to

inter"ret or re&e&ber s"eci+ic details, and they

contained a&biuities and so&e inconsistencies

in the reco&&endations. The deci7 sion to

substantially revise the 3::1 docu&ent was not

taken lihtly. The "resent revised docu&ent was

not based on the results o+ a sinle study butrather on the collective body o+ evidence

"ublished in nu&erous studies over the "ast /

decades. The !o&&ittee souht to construct the

"resent reco&&endations such that they would

be in the best interest




Table %. #rimary Reasons forRe&ision of t'e I( #ro"'yla)is*uidelines

#8 is muc' more liely to result from frequente3posure to random &acteremias associated /it'

daily actiities t'an from &acteremia caused &y adental+ 4# tract+ or 4 tract procedure-

Prop'yla3is may preent an e3ceedingly smallnum&er of cases of #8+ if any+ in indiiduals /'oundergo a dental+ 4# tract+ or 4 tract procedure-

7'e ris of anti&iotic:associated aderse eentse3ceeds t'e &enefit+ if any+ from prop'ylacticanti&iotic t'erapy-

$aintenance of optimal oral 'ealt' and 'ygiene

may reduce t'e incidence of &acteremia from dailyactiities and is more important t'an prop'ylacticanti&iotics for a dental procedure to reduce t'e risof #8-

o+ "atients and "roviders, would be reasonable

and "rudent, and would re"resent the

conclusions o+ "ublished studies and the

collective wisdo& o+ &any e"erts on and

relevant national and international societies.

Potential onse@uences of

$u)stantivehan"es in

Recommendations%ubstantive chanes in reco&&endations couldD3E violate

lon7standin e"ectations and "ractice "atterns2

D/E &ake +ewer "atients eliible +or

"ro"hylais2 D6E reduce &al7 "ractice clai&s

related to "ro"hylais2 and D9E sti&ulate

"ros"ective studies on "ro"hylais. The!o&&ittee and others34 reconize that

substantive chanes in "ro"hylais uidelines

&ay violate lon7standin e"ectations and

"rac7 tice "atterns by "atients and healthcare

"roviders. The !o&7 &ittee reconizes that

these new reco&&endations &ay cause concern

a&on "atients who have "reviously received

anti7 biotic "ro"hylais to "revent be+ore

dental or other "rocedures and are now advised

that such "ro"hylais is unnecessary. Table /

includes the &ain talkin "oints that &ay be

hel"+ul +or clinicians in reeducatin their

"atients about these chanes. To reco&&end

such chanes de&ands due dilience and critical

analysis. or 80 years, since the "ublication o+

the +irst A#A uidelines on the "revention o+

,4

"atients and healthcare "roviders assu&edthat antibiotics ad&inistered in association with

a bactere&ia7"roducin "rocedure e++ectively

"revented in "atients with underly7 in

cardiac risk +actors. Patients were educated

about bactere&ia7"roducin "rocedures and risk

+actors +or , and they e"ected to receive

antibiotic "ro"hylais2 healthcare "roviders,

es"ecially dentists, were e"ected to ad&inister

the&. Patients with underlyin cardiac

conditions that carry a li+eti&e risk o+acuisition o+ , such as &itral valve

"rola"se DMPE, had a sense o+ reassurance and

co&+ort that antibiotics ad&inistered in

association with a dental "roce7 dure were

e++ective and usually sa+e to "revent .

#ealthcare "roviders, es"ecially dentists, +elt a

sense o+ obliation and "ro+essional and leal

res"onsibility to "rotect their "atients +ro&

that &iht result +ro& a "rocedure. *n the basis

o+ reco&&endations in this revised docu&ent,substantially +ewer "atients will be

reco&&ended +or "ro"hylais.

!ases o+ either te&"orally or re&otely

associated with an invasive "rocedure, es"ecially

a dental "rocedure, have +reuently been the

basis +or &al"ractice clai&s aainst healthcare

"roviders. <nlike &any other in+ections +or

which



there is conclusive evidence +or the e++icacy o+

"reventive thera"y, the "revention o+ is not a

"recise science. Because "reviously "ublished

A#A uidelines +or the "revention o+

contained a&biuities and inconsistencies and

were o+ten based on &ini&al "ublished data or

e"ert o"inion, they were sub@ect to con+lictin

inter"retations a&on "atients, health7 care

"roviders, and the leal syste& about "atient

eliibility +or "ro"hylais and whether there was

strict adherence by healthcare "roviders to A#A

reco&&endations +or "ro"hy7 lais. This

docu&ent is intended to identi+y which, i+ any,

"atients &ay "ossibly bene+it +ro&

"ro"hylais and to de+ine, to the etent "ossible,

which dental "rocedures should have

"ro"hylais in this select rou" o+ "atients.

Accord7 inly, the !o&&ittee ho"es that this

docu&ent will result in reater clarity +or

"atients, healthcare "roviders, and consult7 in

"ro+essionals.

The !o&&ittee believes that

reco&&endations +or "ro"hylais &ust be

evidence based. A "lacebo7controlled,

&ulticenter, rando&ized, double7blinded study

to evaluate the e++icacy o+ "ro"hylais in

"atients who undero a dental, G, or G< tract

"rocedure has not been done. %uch a study

would reuire a lare nu&ber o+ "atients "er

treat&ent rou" and standardization o+ the

s"eci+ic invasive "rocedures and the "atient

"o"ulations. This ty"e o+ study would be

necessary to de+initively answer lon7standin

unresolved uestions reardin the e++icacy o+

"ro"hylais. The !o&&ittee ho"es that this

revised docu&ent will sti&ulate additional

studies on the "revention o+ . uture "ublished

data will be reviewed care+ully by the A#A, the

!o&&ittee on $heu&atic ever, ndocarditis,

and Kawasaki -isease, and other societies, and

+urther revisions to the "resent docu&ent will be

based on relevant studies.

Patho"enesis of IEThe develo"&ent o+ is the net result o+the co&"le

interaction between the bloodstrea& "athoen

with &atri &olecules and "latelets at sites o+

endocardial cell da&ae. n addition, &any o+

the clinical &ani+estations o+ e&anate +ro&

the hostOs i&&une res"onse to the in+ectin

&icroor7 anis&. The +ollowin seuence o+

events is thouht to result in 5 +or&ation o+

nonbacterial thro&botic endocarditis D(BTE on

the sur+ace o+ a cardiac valve or elsewhere that

endothelial da&ae occurs, bactere&ia,

adherence o+ the bacteria in the bloodstrea& to

(BT, and "roli+eration o+ bacteria within a

veetation.

Formation of

3?2ETurbulent blood +low "roduced by certain ty"eso+ conenital

or acuired heart disease, such as +low +ro& a

hih7 to a low7"ressure cha&ber or across a

narrowed ori+ice, trau&a7 tizes the endotheliu&.

This creates a "redis"osition +or de"osition o+

"latelets and +ibrin on the sur+ace o+ the

endotheliu&, which results in (BT. nvasion

o+ the blood7 strea& with a &icrobial s"ecies

that has the "athoenic "otential to colonize this

site can then result in .

2ransient

?acteremiaMucosal sur+aces are "o"ulated by a denseendoenous

&icro+lora. Trau&a to a &ucosal sur+ace, "articularly the




inival crevice around teeth, oro"haryn, G

tract, urethra, and vaina, releases &any

di++erent &icrobial s"ecies tran7 siently into the

bloodstrea&. Transient bactere&ia caused by

viridans rou" stre"tococci and other oral

&icro+lora occurs co&&only in association withdental etractions or other dental "rocedures or

with routine daily activities. Althouh

controversial, the +reuency and intensity o+ the

resultin bactere&ias are believed to be related

to the nature and &anitude o+ the tissue trau&a,

the density o+ the &icrobial +lora, and the deree

o+ in+la&&ation or in+ection at the site o+

trau&a. The &icrobial s"ecies enterin the

circulation de"ends on the uniue endoenous

&icro+lora that colonizes the "articulartrau&atized site.

?acterial

Adherence

The ability o+ various &icrobial s"ecies to

adhere to s"eci+ic sites deter&ines the anato&ic

localization o+ in+ection caused by these

&icrooranis&s. Mediators o+ bacterial

adherence serve as virulence +actors in the

"athoenesis o+ . (u&er7 ous bacterial sur+aceco&"onents "resent in stre"tococci,

sta"hylococci, and enterococci have been shown

in ani&al &odels o+ e"eri&ental endocarditis to

+unction as critical adhesins. %o&e viridans

rou" stre"tococci contain a i&A "rotein that is

a li"o"rotein rece"tor antien DLraE that serves

as a &a@or adhesin to the +ibrin "latelet &atri o+

(BT.31 %ta"hylococcal adhesins +unction in at

least / ways. n one, &icrobial sur+ace

co&"onents reconizin adhesive &atri&olecules +acilitate the attach&ent o+

sta"hylococci to hu&an etracellular &atri

"roteins and to &edical devices that beco&e

coated with &atri "roteins a+ter i&"lantation.

n the other, bacterial etracellular structures

contribute to the +or&ation o+ bio+il& that +or&s

on the sur+ace o+ i&"lanted &edical devices. n

both cases, sta"hylococcal adhesins are

i&"ortant virulence +actors.

Both i&A and sta"hylococcal adhesins arei&&unoenic in e"eri&ental in+ections.

accines "re"ared aainst i&A and

sta"hylococcal adhesins "rovide so&e "rotective

e++ect in e"eri&ental endocarditis caused by

viridans rou" stre"to7 cocci and

sta"hylococci. 3=,3: The results o+ these

e"eri&en7 tal studies are hihly intriuin,

because the develo"&ent o+ an e++ective vaccine+or use in hu&ans to "revent viridans rou"

stre"tococcal or sta"hylococcal would be o+

&a@or i&"ortance.

Proliferation of ?acteria (ithin a e"etation

Microoranis&s adherent to the veetation

sti&ulate +urther de"osition o+ +ibrin and

"latelets on their sur+ace. Within this secluded

+ocus, the buried &icrooranis&s &ulti"ly as

ra"7 idly as bacteria in broth cultures to reach&ai&al &icrobial densities o+ 30= to 3033

colony7+or&in units "er ra& o+ veetation

within a short ti&e on the le+t side o+ the heart,

a""arently uninhibited by host de+enses in le+t7

sided lesions. $iht7sided veetations have

lower bacterial densities, which &ay be the

conseuence o+ host de+ense &echanis&s active

at this site, such as "oly&or"honuclear

activity or "latelet7 derived antibacterial

"roteins. More than :0 o+ the &icro7oranis&s in &ature le+t7 or riht7sided valvular

veetations are &etabolically inactive rather

than in an active rowth



"hase and are there+ore less res"onsive to the

bactericidal e++ects o+ antibiotics./0

Rationale for or A"ainst Pro'h#laBis of IE

Historical

?ack"round

iridans rou" stre"tococci are "art o+ the

nor&al skin, oral, res"iratory, and G tract +lora,and they cause at least 80 o+ cases o+

co&&unity7acuired native valve not

associated with intravenous dru use./3 More

than a century ao, the oral cavity was

reconized as a "otential source o+ the

bactere&ia that caused viridans rou"

stre"tococcal . n 3==8, *sler // noted an

association between bactere&ia +ro& surery

and . *kell and lliott/6 in 3:68 re"orted that

33 o+ "atients with "oor oral hyiene had "ositive blood cultures with viridans rou"

stre"tococci and that 43 o+ "atients had

viridans rou" stre"tococcal bactere&ia with

dental etraction.

As a result o+ these early studies and

subseuent studies, durin the "ast 80 years, the

A#A uidelines reco&&ended anti&icrobial

"ro"hylais to "revent in "atients with

underlyin cardiac conditions who underwent

bactere&ia7 "roducin "rocedures on the basiso+ the +ollowin +actors5 D3E bactere&ia causes

endocarditis2 D/E viridans rou" stre"7 tococci

are "art o+ the nor&al oral +lora, and enterococci

are "art o+ the nor&al G and G< tract +lora2 D6E

these &icroor7 anis&s were usually susce"tible

to antibiotics reco&&ended +or "ro"hylais2 D9E

antibiotic "ro"hylais "revents viridans rou"

stre"tococcal or enterococcal e"eri&ental

endocardi7 tis in ani&als2 D8E a lare nu&ber o+

"oorly docu&ented case re"orts i&"licated a

dental "rocedure as a cause o+ 2 D4E in so&e

cases, there was a te&"oral relationshi" between

a dental "rocedure and the onset o+ sy&"to&s o+

2 D1E an awareness o+ bactere&ia caused by

viridans rou" stre"to7 cocci associated with a

dental "rocedure eists2 D=E the risk o+

sini+icant adverse reactions to an antibiotic is

low in an individual "atient2 and D:E &orbidity

and &ortality +ro& are hih. Most o+ these

+actors re&ain valid, but collectively, they do not

co&"ensate +or the lack o+ "ublished data that

de&onstrate a bene+it +ro& "ro"hylais.

?acteremia<Producin" Dental

Procedures

The lare &a@ority o+ "ublished studies have

+ocused on dental "rocedures as a cause o+ and the use o+ "ro"hylactic antibiotics to "revent

in "atients at risk. ew data eist on the risk

o+ or "revention o+ associated with a G or

G< tract "rocedure. Accordinly, the !o&&ittee

undertook a critical analysis o+ "ublished data in

the contet o+ the historical rationale +or

reco&&endin antibiotic "ro"hylais +or

be+ore a dental "rocedure. The +ollowin +actors

were considered5 D3E +reuency, nature,

&anitude, and duration o+ bactere&ia

associated with dental "rocedures2 D/E i&"act o+

dental disease, oral hyiene, and ty"e o+ dental

"rocedure on bactere&ia2 D6E i&"act o+

antibiotic "ro"hylais on bactere7 &ia +ro& a

dental "rocedure2 and D9E the e"osure over ti&e

o+ +reuently occurrin bactere&ia +ro& routine

daily activ7 ities co&"ared with bactere&ia +ro&

various dental "rocedures.



174- Circulation &cto)er 6, 9..

These +actors co&"licated reco&&endations

in "revious A#A uidelines on "revention o+

that suested antibiotic "ro"hylais +or so&e

dental "rocedures but not +or others. The

collective "ublished data suest that the vast

&a@ority o+ dental o++ice visits result in so&ederee o+ bactere&ia2 however, there is no

evidence7based &ethod to decide which

"rocedures should reuire "ro"hylais, because

no data show that the incidence, &anitude, or

duration o+ bactere&ia +ro& any dental

"rocedure increase the risk o+ . Accordinly, it

is not clear which dental "rocedures are &ore or

less likely to cause a transient bactere&ia or

result in a reater &anitude o+ bactere&ia than

that which results +ro& routine dailyactivities such as chewin +ood, tooth brushin,

or +lossin. n "atients with underlyin

cardiac conditions, li+elon antibiotic thera"y

is not reco&&ended to "revent that &iht

result +ro& bactere&ias associated with routine

daily activities.8 n "atients with dental disease,

the +ocus on the +reuency o+ bactere&ia

associated with a s"eci+ic dental "rocedure

and the A#A uidelines +or "revention o+

have resulted in an overe&"hasis on antibiotic "ro"hylais and an undere&"hasis on

&aintenance o+ ood oral hyiene and access

to routine dental care, which are likely &ore

i&"ortant in reducin the li+eti&e risk o+ than

the ad&inistration o+ antibiotic "ro"hylais +or a

dental "rocedure. #owever, no

observational or controlled studies su""ort thiscontention.

($)act o# %nti.iotic ,hera)y on

Bactere$ia Fro$ a "ental 'rocedureThe ability o+ antibiotic thera"y to "revent orreduce the

+reuency, &anitude, or duration o+ bactere&ia

associated with a dental "rocedure is

controversial. /9,19 %o&e studies re"orted that

antibiotics ad&inistered be+ore a dental "roce7

dure reduced the +reuency, nature, and;or

duration o+ bac7 tere&ia,86,18,14 whereas others did

not./9,44,11,1= $ecent studies suest thata&oicillin thera"y has a statistically sini+icant

i&"act on reducin the incidence, nature, and

duration o+ bactere&ia +ro& dental "rocedures,

but it does not eli&inate bactere&ia.8/,86,14

#owever, no data show that such a reduc7 tion as

a result o+ a&oicillin thera"y reduces the risk o+

or "revents . #all et al1= re"orted that neither

"enicillin nor a&oicillin thera"y wase++ective in reducin the +reuency o+ bactere&ia

co&"ared with untreated control sub@ects. n

"atients who underwent a dental etraction,

"enicillin or a&"icillin thera"y co&"ared with

"lacebo di&inished the "ercentae o+ viridans

rou" stre"tococci and anaerobes in culture, but

there was no sini+icant di++erence in the

"ercent7 ae o+ "atients with "ositive cultures 30

&inutes a+ter tooth eGtraction./9,44 n a se"arate

study, #all et al11

re"orted that ce+aclor7treated "atients did not have a reduction o+ "ost"ro7

cedure bactere&ia co&"ared with untreated

control sub@ects. !ontradictory "ublished results

+ro& / studies showed reduc7 tion o+

"ost"rocedure bactere&ia by erythro&ycin in

one18 but lack o+ e++icacy +or erythro&ycin or

clinda&ycin in another.1= inally, results are

contradictory with reard to the e++icacy o+ the

use o+ to"ical antise"tics in reducin the

+reuency o+ bactere&ia associated with dental "rocedures, but the "re"onderance o+ evidence

suests that there is no clear bene+it. *ne study

re"orted that chlorheidine and "ovidone iodine

&outh rinse were e++ective,1: whereas others



showed no statistically sini+icant bene+it.8/,=0

To"ical anti7 se"tic rinses do not "enetrate

beyond 6 && into the "eriodon7 tal "ocket and

there+ore do not reach areas o+ ulcerated tissue

where bacteria &ost o+ten ain entrance to the

circulation. *n the basis o+ these data, it is

unlikely that to"ical antise"tics are e++ective to

sini+icantly reduce the +reuency, &anitude,

and duration o+ bactere&ia associated with a

dental "rocedure.

umulative Risk &ver 2ime of?acteremias From Routine Dail#Activities om'ared (ith the?acteremia From a Dental Procedure

Guntheroth=3 esti&ated a cu&ulative e"osure o+

8610 &in7 utes o+ bactere&ia over a 37&onth

"eriod in dentulous "atients resultin +ro&

rando& bactere&ia +ro& chewin +ood and

+ro& oral hyiene &easures, such as tooth

brushin and +lossin, and co&"ared that with a

duration o+ bactere&ia lastin 4 to 60 &inutes

associated with a sinle tooth etraction.

$oberts4/ esti&ated that tooth brushin / ti&es

daily +or 3 year had a 389 000 ti&es reater risk

o+ e"osure to bactere&ia than that resultin

+ro& a sinle tooth etrac7 tion. The cu&ulative

e"osure durin 3 year to bactere&ia +ro&

routine daily activities &ay be as hih as 8.4&illion ti&es reater than that resultin +ro& a

sinle tooth etrac7 tion, the dental "rocedure

re"orted to be &ost likely to cause a

bactere&ia.4/

-ata eist +or the duration o+ bactere&ia +ro&

a sinle tooth etraction, and it is "ossible to

esti&ate the annual cu&ulative e"osure +ro&

dental "rocedures +or the averae individual.

#owever, calculations +or the incidence, nature,

and duration o+ bactere&ia +ro& routine daily

activities are at best rouh esti&ates, and it is

there+ore not "ossible to co&"are "recisely the

cu&ulative &onthly or annual duration o+

e"osure +or bactere&ia +ro& dental "rocedures

co&"ared with routine daily activities.

(evertheless, even i+ the esti7 &ates o+

bactere&ia +ro& routine daily activities are o++

by a +actor o+ 3000, it is likely that the +reuency

and cu&ulative duration o+ e"osure to

bactere&ia +ro& routine daily events over 3 year

are &uch hiher than those that result +ro&

dental "rocedures.

Results of linical $tudies of IE

Pro'h#laBis forDentalProcedures

(o "ros"ective, rando&ized, "lacebo7controlledstudies eist on the e++icacy o+ antibiotic

"ro"hylais to "revent in "atients who

undero a dental "rocedure. -ata +ro& "ub7

lished retros"ective or "ros"ective case7control

studies are li&ited by the +ollowin +actors5 D3E

the low incidence o+ , which reuires a lare

nu&ber o+ "atients "er cohort +or statistical

sini+icance2 D/E the wide variation in the ty"es

and severity o+ underlyin cardiac conditions,

which would re7 uire a lare nu&ber o+ "atientswith s"eci+ic &atched control sub@ects +or each

cardiac condition2 and D6E the lare variety o+

invasive dental "rocedures and dental disease

states, which would be di++icult to standardize

+or control rou"s. These and other li&itations

co&"licate the inter"retation o+ the results o+

"ublished studies o+ the e++icacy o+

"ro"hylais in "atients who undero dental

"rocedures.




Althouh so&e retros"ective studies suested

that there was a bene+it +ro& "ro"hylais, these

studies were s&all in size and re"orted

insu++icient clinical data. urther&ore, in a

nu&ber o+ cases, the incubation "eriod between

the dental "rocedure and the onset o+ sy&"to&so+ was "roloned.=0,=/N =9

van der Meer and colleaues=8 "ublished a

study o+ dental "rocedures in the (etherlands

and the e++icacy o+ antibiotic "ro"hylais to

"revent in "atients with native or "rosthetic

cardiac valves. They concluded that dental or

other "roce7 dures "robably caused only a s&all

+raction o+ cases o+ and that "ro"hylais

would "revent only a s&all nu&ber o+ cases

even i+ it were 300 e++ective. These sa&eauthors=4 "er+or&ed a /7year case7control study.

A&on "atients +or who& "ro"hy7 lais was

reco&&ended, 8 o+ /0 cases o+ occurred

des"ite receivin antibiotic "ro"hylais. The

authors concluded that "ro"hylais was not

e++ective. n a se"arate study,=1 these authors

re"orted "oor awareness o+ reco&&endations +or

"ro7 "hylais a&on both "atients and

healthcare "roviders.

%tro& and colleaues

/

evaluated dental "ro"hylais and cardiac risk +actors in a

&ulticenter case7control study. These authors

re"orted that MP, conenital heart disease

D!#-E, rheu&atic heart disease D$#-E, and

"revious cardiac valve surery were risk +actors

+or the develo"&ent o+ . n that study, control

sub@ects without were &ore likely to have

underone a dental "rocedure than were those

with cases o+ D P 0.06E. The authors

concluded that dental treat&ent was not a risk

+actor +or even in "atients with valvular heart

disease and that +ew cases o+ could be

"revented with "ro"hylais even i+ it were 300

e++ective.

These studies are in aree&ent with a recently

"ublished rench study o+ the esti&ated risk o+

in adults with "redis7 "osin cardiac

conditions who underwent dental "rocedures

with or without antibiotic "ro"hylais.== These

authors con7 cluded that a hue nu&ber o+

"ro"hylais doses would be necessary to "revent

a very low nu&ber o+ cases.

A)solute Risk of IE Resultin" From a

DentalProcedure (o "ublished data accurately deter&ine theabsolute risk o+

that results +ro& a dental "rocedure. *nestudy re"orted that 30 to /0 o+ "atients with

caused by oral +lora underwent a "recedin

dental "rocedure Dwithin 60 or 3=0 days o+

onsetE.=8 The evidence linkin bactere&ia

associated with a dental "rocedure with is

larely circu&stantial, and the nu&ber o+ cases

related to a dental "rocedure is overes7 ti&ated

+or a nu&ber o+ reasons. or 40 years, noted

o"inion leaders in &edicine suested a link

between bactere&ia7 causin dental "roceduresand ,/6 and +or 80 years, the A#A "ublished

reularly u"dated uidelines that e&"hasized the

association between dental "rocedures and

and reco&7 &ended antibiotic "ro"hylais.3

Additionally, bactere&ia7 "roducin dental

"rocedures are co&&on2 it is esti&ated that at

least 80 o+ the "o"ulation in the <nited %tates

visits a dentist at least once a year. urther&ore,

there are nu&erous "oorly docu&ented case

re"orts that i&"licate dental "roce7 duresassociated with the develo"&ent o+ , but these

re"orts did not "rove a direct causal relationshi".

ven in the event o+ a close te&"oral

relationshi" between a dental "rocedure and



, it is not "ossible to deter&ine with certainty

whether the bactere&ia that caused oriinated

+ro& a dental "rocedure or +ro& a rando&ly

occurrin bactere&ia as a result o+ routine daily

activities durin the sa&e ti&e "eriod. Many

case re"orts and reviews have included cases

with a re&ote "recedin dental "rocedure, o+ten

6 to 4 &onths be+ore the dianosis o+ . %tudies

suest that the ti&e +ra&e between bactere&ia

and the onset o+ sy&"to&s o+ is usually 1 to

39 days +or viridans rou" stre"tococci or

enterococci. $e"ortedly,

1= o+ such cases o+ occur within 1 days o+ bactere&ia and

=8 within 39 days.=: Althouh the u""er ti&e

li&it is not known, it is likely that &any cases o+

with incubation "eriods loner than / weeks

a+ter a dental "rocedure were incorrectly

attributed to the "rocedure. These and other+actors have led to a heihtened awareness

a&on "atients and healthcare "roviders o+ the

"ossible association between dental "rocedures

and , which likely has led to substantial

overre"ortin o+ cases attributable to dental

"rocedures.

Althouh the absolute risk +or +ro& a dental

"rocedure is i&"ossible to &easure "recisely,

the best available esti7 &ates are as +ollows5 +

dental treat&ent causes 3 o+ all cases o+viridans rou" stre"tococcal annually in the

<nited %tates, the overall risk in the eneral

"o"ulation is esti&ated to be as low as 3 case o+

"er 39 &illion dental "rocedures.93,:0,:3 The

esti&ated absolute risk rates +or +ro& a dental

"rocedure in "atients with underlyin cardiac

conditions are as +ollows5 MP, 3 "er 3.3

&illion "rocedures2 !#-, 3 "er 918 0002 $#-,

3 "er 39/ 0002 "resence o+ a "rosthetic cardiac

valve, 3 "er 339 0002 and "revious , 3 "er

:8 000 dental "rocedures.93,:3 Althouh these

calculations o+ risk are esti&ates, it is likely that

the nu&ber o+ cases o+ that result +ro& a

dental "rocedure is eceedinly s&all.

There+ore, the nu&ber o+ cases that could be

"revented by antibiotic "ro"hylais, even i+

300 e++ective, is si&ilarly s&all. *ne would

not e"ect antibiotic "ro"hylais to be near

300 e++ective, however, because o+ the nature

o+ the oranis&s and choice o+ antibiotics.

Risk of Adverse Reactions and ost<Effectiveness of Pro'h#lactic 2hera'# (on+atal adverse reactions, such as rash,diarrhea, and G

u"set, occur co&&only with the use o+

anti&icrobials2 however, only sinle7dose

thera"y is reco&&ended +or dental "ro"hylais,

and these co&&on adverse reactions are usually

not severe and are sel+7li&ited. atalana"hylactic reactions were esti&ated to occur

in 38 to /8 individuals "er 3 &illion "atients

who receive a dose o+ "enicillin.:/,:6 A&on

"atients with a "rior "enicillin use, 64 o+

+atalities +ro& ana"hylais occurred in those

with a known allery to "enicillin co&"ared

with 49 o+ +atalities a&on those with no

history o+ "enicillin allery.:9 These calculations

are at best rouh esti&ates and &ay overesti&ate

the true risk o+ death caused by +atal ana"hylais+ro& ad&inistration o+ a "enicillin. They are

based on retros"ective reviews or surveys o+

"atients or on healthcare "rovidersO recall o+

events. A "ros"ective study is necessary to

accurately deter&ine the risk o+ +atal ana"hy7

lais resultin +ro& ad&inistration o+ a

"enicillin.

or 80 years, the A#A has reco&&ended a

"enicillin as the "re+erred choice +or dental

"ro"hylais +or . -urin these




80 years, the !o&&ittee is unaware o+ any cases

re"orted to the A#A o+ +atal ana"hylais

resultin +ro& the ad&inistra7 tion o+ a "enicillin

reco&&ended in the A#A uidelines +or

"ro"hylais. The !o&&ittee believes that a

sinle dose o+ a&oicillin or a&"icillin is sa+eand is the "re+erred "ro"hy7 lactic aent +or

individuals who do not have a history o+ ty"e

hy"ersensitivity reaction to a "enicillin, such as

ana"hy7 lais, urticaria, or anioede&a. atal

ana"hylais +ro& a ce"halos"orin is esti&ated to

be less co&&on than +ro& "enicillin, at

a""roi&ately 3 case "er 3 &illion "atients.:8

atal reactions to a sinle dose o+ a &acrolide or

clinda&ycin are etre&ely rare.:4,:1 There has

been only 3 case re"ort o+ docu&entedClostridium difficile colitis a+ter a sinle dose o+

"ro"hylactic clinda&ycin.:=

$ummar

#Althouh it has lon been assu&ed that dental "rocedures

&ay cause in "atients with underlyin cardiac

risk +actors and that antibiotic "ro"hylais is

e++ective, scienti+ic "roo+ is lackin to su""ort

these assu&"tions. The collective "ub7 lishedevidence suests that o+ the total nu&ber o+

cases o+ that occur annually, it is likely that

an eceedinly s&all nu&ber are caused by

bactere&ia7"roducin dental "roce7 dures.

Accordinly, only an etre&ely s&all nu&ber o+

cases o+ &iht be "revented by antibiotic

"ro"hylais even i+ it were 300 e++ective. The

vast &a@ority o+ cases o+ caused by oral

&icro+lora &ost likely result +ro& rando&

bactere7 &ias caused by routine daily activities,such as chewin +ood, tooth brushin, +lossin,

use o+ tooth"icks, use o+ water irriation

devices, and other activities. The "resence o+

dental disease &ay increase the risk o+

bactere&ia associated with these routine

activities. There should be a shi+t in e&"hasis

away +ro& a +ocus on a dental "rocedure and

antibiotic "ro"hylais toward a reater e&"hasis

on i&"roved access to dental care and oral

health in "atients with underlyin cardiacconditions associated with the hihest risk o+

adverse out7 co&e +ro& and those conditions

that "redis"ose to the acuisition o+ .

ardiac onditions and Endocarditis

Previous A#A uidelines cateorized

underlyin cardiac conditions associated with

the risk o+ as those with hih risk, &oderate

risk, and neliible risk and reco&&ended

"ro"hylais +or "atients in the hih7 and

&oderate7risk cateories.3 or the "resent

uidelines on "revention o+ , the !o&&ittee

considered 6 distinct issues5 D3E What under7

lyin cardiac conditions over a li+eti&e have

the hihest "redis"osition to the acuisition o+

endocarditisJ D/E What underlyin cardiac

conditions are associated with the hihest risk

o+ adverse outco&e +ro& endocarditisJ D6E

%hould reco&&endations +or "ro"hylais be

based on either or both o+ these / conditionsJ

0nderl#in" onditions &ver a 1ifetime 2hatHave the Hi"hest Predis'osition to theAc@uisitionofEndocarditisn *l&sted !ounty, Minnesota, the incidence o+ in adults

raned +ro& 8 to 1 cases "er 300 000 "erson7

years.:: This incidence has re&ained stable

durin the "ast 9 decades and



is si&ilar to that re"orted in other studies. 300 N306

Previously, $#- was the &ost co&&on

underlyin condition "redis"os7 in to

endocarditis, and $#- is still co&&on in

develo"in countries.:: n develo"ed countries,

the +reuency o+ $#- has declined, and MP is

now the &ost co&&on underlyin condition in

"atients with endocarditis.309

ew "ublished data uantitate the li+eti&e risk

o+ acuisi7 tion o+ associated with a s"eci+ic

underlyin cardiac condition. %teckelber and

Wilson:0 re"orted the li+eti&e risk o+ acuisition

o+ , which raned +ro& 8 "er 300 000

"atient7years in the eneral "o"ulation with no

known cardiac conditions to /340 "er 300 000

"atient7years in "atients who underwent

re"lace&ent o+ an in+ected "rosthetic cardiac

valve. n that study,:0 the risk o+ "er 300 000

"atient7years was 9.4 in "atients with MPwithout an audible cardiac &ur&ur and 8/ in

"atients with MP with an audible &ur&ur o+

&itral reuritation. Per 300 000 "atient7years,

the li+eti&e risk D6=0 to 990E +or $#- was

si&ilar to that D60= to 6=6E +or "atients with a

&echanical or bio"rosthetic cardiac valve. The

hihest li+eti&e risks "er 300 000 "atient7

years were as +ollows5 cardiac valve

re"lace&ent surery +or native valve , 4602

"revious , 1902 and "rosthetic valvere"lace&ent done in "atients with "rosthetic

valve endocarditis, /340. n a se"arate study, the

risk o+ "er 300 000 "atient7years was

/13 in "atients with conenital aortic stenosis

and 398 in "atients with ventricular se"tal

de+ect.308 n that sa&e study, the risk o+ be+ore

closure o+ a ventricular se"tal de+ect was &ore

than twice that a+ter closure. Althouh these data

"rovide use+ul ranes o+ risk in lare

"o"ulations, it is di++icult to utilize the& to

de+ine accurately the li+eti&e risk o+ acuisition

o+ in an individual "atient with a s"eci+ic

underlyin cardiac risk +actor. This di++iculty is

based in "art on the +act that each individual

cardiac condition, such as $#- or MP,

re"resents a broad s"ectru& o+ "atholoy +ro&

&ini&al to severe, and the risk o+ would

likely be in+luenced by the severity o+ valvular

disease.

!#- is another underlyin condition with

&ulti"le di++er7 ent cardiac abnor&alities that

rane +ro& relatively &inor to severe, co&"le

cyanotic heart disease. -urin the "ast /8 years,

there has been an increasin use o+ various

intracardiac valvular "rostheses and

intravascular shunts, ra+ts, and other devices

+or re"air o+ valvular heart disease and !#-.

The diversity and nature o+ these "rostheses and

"rocedures likely "resent di++erent levels o+ risk+or acuisition o+ . These +actors co&"licate

an accurate assess&ent o+ the true li+eti&e risk

o+ acuisition o+ in "atients with a s"eci+ic

underlyin cardiac condition.

*n the basis o+ the data +ro& %teckelber and

Wilson:3 and others,/ it is clear that the

underlyin conditions discussed above re"resent

a li+eti&e increased risk o+ acuisition o+

co&"ared with individuals with no known

underlyin cardiac condition. Accordinly, whenutilizin "revious A#A uide7 lines in the

decision to reco&&end "ro"hylais +or a

"atient scheduled to undero a dental, G tract,

or G< tract "rocedure, healthcare "roviders were

reuired to base their decision on "o"ulation7

based studies o+ risk o+ acuisition o+ that

&ay or &ay not be relevant to their s"eci+ic

"atient. urther&ore, "ractitioners had to weih

the "otential e++icacy o+ "ro"hylais in a

"atient who &ay neither need nor



(ilson et al Prevention of Infective Endocarditis 174/

Table +. ,ardiac ,onditions Associated it't'e Hig'est Ris. of Ad&erse /utcome From(ndocarditis for 'ic' #ro"'yla)is it' ental#rocedures Is Reasonable

Prost'etic cardiac ale or prost'etic material used

for cardiac ale repair Pre(ious #8

;ongenital 'eart disease (;<D)

nrepaired cyanotic ;<D+ including palliaties'unts and conduits

;ompletely repaired congenital 'eart defect /it'prost'etic material or deice+ /'et'er placed &ysurgery or &y cat'eter interention+ during t'e first6 mont's after t'e procedure=

Repaired ;<D /it' residual defects at t'e site orad>acent to t'e site of a prost'etic patc' orprost'etic deice (/'ic' in'i&it endot'eliali?ation)

;ardiac transplantation recipients /'o deelopcardiac alulopat'y

83cept for t'e conditions listed a&oe+ anti&ioticprop'yla3is is no longer recommended for any ot'erform of ;<D-

=Prop'yla3is is reasona&le &ecause

endot'eliali?ation of prost'etic material occurs

/it'in 6 mont's after t'e procedure-

bene+it +ro& such thera"y aainst the risk o+

adverse reaction to the antibiotic "rescribed.

inally, healthcare "roviders had to consider the

"otential &edicoleal risk o+ not "rescribin

"ro"hylais. or dental "rocedures, there is a

rowin body o+ evidence that suests that

"ro"hylais &ay "revent only an eceedinly

s&all nu&ber o+ cases o+ , as discussed in

detail above.

ardiac onditions Associated (ith the

Hi"hest Risk of Adverse &utcome From

Endocarditis ndocarditis, irres"ective o+ the

underlyin cardiac condition, is a serious, li+e7

threatenin disease that was always +atal in the

"reantibiotic era. Advances in anti&icrobial

thera"y, early reconition and &anae&ent o+

co&"lications o+ , and i&"roved surical

technoloy have reduced the &orbidity and

&ortality o+ . (u&erous co&orbid +actors,

such as older ae, diabetes &ellitus,

i&&unosu""ressive conditions or thera"y, and

dialysis, &ay co&"licate . ach o+ these

co&orbid conditions inde"endently increases

the risk o+ adverse outco&e +ro& , and they

o+ten occur in co&bina7 tion, which +urther

increases &orbidity and &ortality rates.Additionally, there &ay be lon7ter&

conseuences o+ . *ver ti&e, the cardiac valve

da&aed by &ay undero "roressive

+unctional deterioration that &ay result in the

need +or cardiac valve re"lace&ent.

n native valve viridans rou" stre"tococcal or

enterococcal , the s"ectru& o+ disease &ay

rane +ro& a relatively benin in+ection to

severe valvular dys+unction, dehiscence,

conestive heart +ailure, &ulti"le e&bolicevents, and death2 however, the underlyin

conditions shown in Table 6 virtually always

have an increased risk o+ adverse outco&e. or

ea&"le, "atients with viridans rou"

stre"tococcal "rosthetic valve endocarditis have

a &ortality rate o+ /0 or reater,304 N30: whereas

the &ortality +ro& "atients with viridans rou"

stre"tococcal native valve is 8 or less.30=,330 N

334 %i&ilarly, the &ortality o+ enterococcal

"rosthetic valve endocarditis is hiher than thato+ native valve enterococcal B.301,30=,339,331

Moreover, "atients with "rosthetic valve

endocarditis are &ore likely than those with

native valve endocarditis to develo" heart

+ailure, the need +or cardiac valve re"lace&ent

surery, "erivalvular etension o+ in+ection, and

other co&"lications.




dures is reasonable, even thouh we

acknowlede that its e++ectiveness is unknown

8Class ((a * B>.

!o&"ared with "revious A#A uidelines,

under these revised uidelines, &any +ewer

"atients would be candidates to receive "ro"hylais. We believe that these revised

uidelines are in the best interest o+ "atients and

healthcare "roviders and are based on the best

available "ublished data and e"ert o"inion.

Additionally, the chane in e&"hasis to restrict

"ro"hylais +or only those "atients with the

hihest risk o+ adverse outco&e should reduce

the uncertainties a&on "atients and "roviders

about who should receive "ro"hylais. MP is

the &ost co&&on underlyin condition that "redis"oses to acuisition o+ in the Western

world2 however, the absolute incidence o+

endocarditis is etre&ely low +or the entire

"o"ulation with MP, and it is not usually

associated with the rave outco&e associated

with the con7 ditions identi+ied in Table 6.

Thus, "ro"hylais is no loner

reco&&ended +or this rou" o+ individuals.

inally, the ad&inistration o+ "ro"hylactic

antibiotics is not risk +ree, as discussed above.Additionally, the wides"read use o+ antibiotic

thera"y "ro&otes the e&erence o+ resistant

&icrooranis&s &ost likely to cause

endocarditis, such as viridans rou" stre"tococci

and enterococci. The +reuency o+ &ultidru7

resistant viridans rou" stre"tococci and entero7

cocci has increased dra&atically durin the "ast

/ decades. This increased resistance has reduced

the e++icacy and nu&7 ber o+ antibiotics available

+or the treat&ent o+ .

Anti)iotic Re"imens

General

Princi'lesAn antibiotic +or "ro"hylais should bead&inistered in a

sinle dose be+ore the "rocedure. + the dosae

o+ antibiotic is inadvertently not ad&inistered

be+ore the "rocedure, the dosae &ay be

ad&inistered u" to / hours a+ter the "rocedure.

#owever, ad&inistration o+ the dosae a+ter the "rocedure should be considered only when the

"atient did not receive the "re7"rocedure dose.

%o&e "atients who are scheduled +or an invasive

"rocedure &ay have a coincidental endocarditis.

The "resence o+ +ever or other &ani+estations o+

syste&ic in+ection should alert the "rovider to

the "ossibility o+ . n these circu&stances, it is

i&"ortant to obtain blood cultures and otherrelevant tests be+ore ad&inistration o+ antibiotics

intended to "revent . ailure to do so &ay

result in delay in dianosis or treat&ent o+ a

conco&itant case o+ .

Re"imens for Dental

ProceduresPrevious A#A uidelines on "ro"hylais listed asubstantial

nu&ber o+ dental "rocedures and events +or

which antibiotic "ro"hylais was reco&&endedand those "rocedures +or which "ro"hylais was

not reco&&ended. *n the basis o+ a critical

review o+ the "ublished data, it is clear that

transient viridans rou" stre"tococcal bactere&ia

&ay result +ro& any dental "rocedure that

involves &ani"ulation o+ the inival or

"eria"ical reion o+ teeth or "er+oration o+ the

oral &ucosa. t cannot be assu&ed that

&ani"ulation o+ a healthy7a""earin &outh or a

&ini&ally invasive dental "rocedure reduces thelikelihood o+ a bactere&ia. There+ore, antibiotic

"ro"hylais is reasonable +or "atients with the

conditions listed in Table 6 who undero any

dental "rocedure that involves the inival



Table 0. ental #rocedures for 'ic'(ndocarditis#ro"'yla)is Is Reasonable for#atients in Table +

All dental procedures t'at inole manipulation of

gingial tissue or t'e periapical region of teet' orperforation of t'e oral mucosa

7'e follo/ing procedures and eents do notneed prop'yla3is2 routine anest'etic in>ections

t'roug' noninfected tissue+ taing dental

radiograp's+ placement of remoa&le prost'odontic

or ort'odontic appliances+ ad>ustment of ort'odontic

appliances+ placement of ort'odontic &racets+

s'edding of deciduous teet'+ and &leeding from

trauma to t'e lips or oral mucosa-

tissues or "eria"ical reion o+ a tooth and +orthose "rocedures that "er+orate the oral &ucosa

DTable 9E. Althouh "ro7 "hylais is

reasonable +or these "atients, its e++ectiveness is

unknown 8Class ((a * C >. This includes

"rocedures such as bio"sies, suture re&oval, and

"lace&ent o+ orthodontic bands, but it does not

include routine anesthetic in@ections throuh

nonin+ected tissue, the takin o+ dental

radiora"hs, "lace&ent o+ re&ovable

"rosthodontic or orthodontic a""li7 ances, "lace&ent o+ orthodontic brackets, or

ad@ust&ent o+ orthodontic a""liances. inally,

there are other events that are not dental

"rocedures and +or which "ro"hylais is not

reco&&ended, such as sheddin o+ deciduous

teeth and trau&a to the li"s and oral &ucosa.

n this li&ited "atient "o"ulation, "ro"hylactic

anti&icro7 bial thera"y should be directed

aainst viridans rou" stre"7 tococci. -urin the

"ast / decades, there has been a sini+i7 cantincrease in the "ercentae o+ strains o+ viridans

rou" stre"tococci resistant to antibiotics

reco&&ended in "revious A#A uidelines +or

the "revention o+ . Prabhu et al368 studied

susce"tibility "atterns o+ viridans rou"

stre"tococci recovered +ro& "atients with

dianosed durin a "eriod +ro& 3:13 to 3:=4

and co&"ared these susce"tibilities with those o+

viridans rou" stre"tococci +ro& "atients with

dianosed +ro& 3::9 to /00/. n that study,

none o+ the strains o+ viridans rou" stre"tococci

were "enicillin resistant in the early ti&e "eriod

co&"ared with 36 o+ strains that were

inter&ediately or +ully "enicillin resistant durin

the later ti&e "eriod. n that study, &acrolide

resistance increased +ro& 33 to /4 and

clinda&ycin resistance +ro& 0 to 9. A&on

68/ blood culture isolates o+ viridans rou"

stre"7 tococci, resistance rates were 36 +or

"enicillin, 38 +or a&oicillin, 31 +or

ce+triaone, 6= +or erythro&ycin, and

:4 +or ce"halein.364 The rank order o+

decreasin level o+ activity o+ ce"halos"orins inthat study was ce+"odoi&e eual to ce+triaone,

reater than ce+"rozil, and eual to ce+uroi&e,

and ce"halein was the least active. n other

studies, resistance o+ viridans rou" stre"tococci

to "enicillin raned +ro& 31 to 80M361N39/ and

resistance to ce+triaone raned +ro& // to

9/M.363,390 !e+triaone was / to 9 ti&es &ore

active in vitro than ce+azolin.363,390 %i&ilarly hih

rates o+ resistance were re"orted +or &acrolides,

ranin +ro& // to 8=M361,393,396,3992 resistanceto clinda&ycin raned +ro&

36 to

/1.3/=,3/:,363,361,

36=,390

Most o+ the strains o+ viridans rou"

stre"tococci in the above7cited studies were

recovered +ro& "atients with serious underlyin

illnesses, includin &alinancies and +ebrile

neu7 tro"enia. These "atients are at increased

risk o+ in+ection and colonization by &ulti"le7

druNresistant &icrooranis&s, in7 cludin

viridans rou" stre"tococci. Accordinly,

these




Table 5. Regimens for a ental#rocedure

Regimen2 ingle Dose %0to 60 min

@efore Procedure

ituation Ag Adults ;'ildren

.ral Amo3icillin

50 mg9g

na&le to tae oral medication Ampici

llin/

! g #$ or #5

1 g #$ or #5

50 mgg #$ or

#

Allergic to penicillins or ampicillinBoral ;ep'ale3i

n= /R;lindamy

cin /R A?it'rom ycin or

!g

600mg

50 mg9g

!0 mg9g

15 mg9g

Allergic to penicillins or ampicillin and una&le to

tae oral medication;efa?olin orceftria3one=

/

1 g #$ or#5

#

50 mgg #$ or#

#$ indicates intramuscularC #+ intraenous-.r ot'er first: or second:generation oral cep'alosporin in equialent adult or pediatric dosage-

=;ep'alosporins s'ould not &e used in an indiidual /it' a 'istory of anap'yla3is+ angioedema+ or urticaria /it' penicillins or ampicillin-

strains &ay not be re"resentative o+

susce"tibility "atterns o+ viridans rou"

stre"tococci recovered +ro& "resu&ably nor7

&al individuals who undero a dental "rocedure.

-ieke&a et al361 re"orted that 6/ o+ strains o+

viridans rou" stre"to7 cocci were resistant to

"enicillin in "atients without cancer. Kin et al399

re"orted erythro&ycin resistance in 93 o+

stre"tococci recovered +ro& throat cultures in

otherwise healthy individuals who "resentedwith &ild res"iratory tract in+ections. n that

study, a+ter treat&ent with either azithro7 &ycin

or clinda&ycin, the "ercentae o+ resistant

stre"tococci increased to =/ and 13,

res"ectively. Accordinly, the resistance rates o+

viridans rou" stre"tococci are si&ilarly hih in

otherwise healthy individuals and in "atients

with serious underlyin diseases.

The i&"act o+ viridans rou" stre"tococcal

resistance on antibiotic "revention o+ isunknown. + resistance in vitro is "redictive o+

lack o+ clinical e++icacy, the hih resistance rates

o+ viridans rou" stre"tococci "rovide additional

su""ort +or the assertion that "ro"hylactic

thera"y +or a dental "rocedure is o+ little, i+ any,

value. t is i&"ractical to reco&&end

"ro"hylais with only those antibiotics, such as

vanco&ycin or a +luorouin7 olone, that are

hihly active in vitro aainst viridans rou"

stre"tococci. There is no evidence that suchthera"y is e++ective +or "ro"hylais o+ , and

their use &iht result in the develo"7 &ent o+

resistance o+ viridans rou" stre"tococci and

other &icrooranis&s to these and other

antibiotics.

n Table 8, a&oicillin is the "re+erred choice

+or oral thera"y because it is well absorbed in the

G tract and "rovides hih and sustained seru&

concentrations. or indi7 viduals who are alleric

to "enicillins or a&oicillin, the use o+

ce"halein or another +irst7eneration oral

ce"halos"orin, clinda&ycin, azithro&ycin, orclarithro&ycin is reco&7 &ended. ven thouh

ce"halein was less active aainst viridans rou"

stre"tococci than other +irst7eneration oral

ce"halos"orins in 3 study,364 ce"halein is

included in Table

8. (o data show su"eriority o+ 3 oral

ce"halos"orin over another +or "revention o+ ,

and eneric ce"halein is widely available and

relatively ine"ensive. Because o+ "ossible

cross7reactions, a ce"halos"orin should not bead&inistered




tract in+ections, "articularly in older &ales with

"rostatic hy"ertro7 "hy and obstructive uro"athy

or "rostatitis.

The ad&inistration o+ "ro"hylactic antibiotics

solely to "re7 vent endocarditis is not

reco&&ended +or "atients who undero G< orG tract "rocedures, includin dianostic

eso"ha7 oastroduodenosco"y or colonosco"y

8Class ((( * B>. This is in contrast to

"revious A#A uidelines that listed G or G<

tract "rocedures +or which "ro"hylais was

reco&&ended and those +or which "ro"hylais

was not reco&&ended.3 A lare nu&ber o+

dianostic and thera"eutic "rocedures that

involve the G, he"atobiliary, or G< tract &ay

cause transient enterococcal bactere&ia. The

"ossible association between G or G< tract

"roce7 dures and has not been studied as

etensively as the "ossible association with

dental "rocedures.398 The cases o+ te&"orally

associated with a G or G< tract "roce7 dure are

anecdotal, with either a sinle or very s&all

nu&ber o+ cases re"orted.=6 (o "ublished data

de&onstrate a conclusive link between

"rocedures o+ the G or G< tract and the

develo"&ent o+ .398 Moreover, no studies eist

that de&onstrate that the ad&inistration o+

anti&icrobial "ro"hylais "revents in

association with "rocedures "er+or&ed on the G

or G< tract.

There has been a dra&atic increase in the

+reuency o+ anti&icrobial7resistant strains o+

enterococci to "enicillins, vanco7 &ycin, and

a&inolycosides.394 N383 These antibiotics were

reco&7 &ended +or "ro"hylais in "reviousA#A uidelines.3 The sini+icance o+ the

increased +reuency o+ &ultiresistant strains o+

enterococci on "revention o+ in "atients who

undero G or G< tract "rocedures is unknown.

The hih "revalence o+ resistant strains o+

enterococci adds +urther doubt about the e++icacy

o+ "ro"hylactic thera"y +or G or G< tract

"rocedures.

Patients with in+ections o+ the G or G< tract

&ay have inter&ittent or sustained enterococcal bactere&ia. or "atients with the conditions

listed in Table 6 who have an established G or

G< tract in+ection or +or those who receive

antibiotic thera"y to "revent wound in+ection or

se"sis associated with a G or G< tract

"rocedure, it &ay be reasonable that the

antibiotic rei&en include an aent active

aainst enterococci, such as "enicillin,a&"icillin, "i"eracillin, or vanco&ycin 8Class

((. * B>2 however, no "ublished studies

de&onstrate that such thera"y would "revent

enterococcal .

or "atients with the conditions listed in Table

6 scheduled +or an elective cystosco"y or other

urinary tract &ani"ulation who have an

enterococcal urinary tract in+ection or coloniza7

tion, antibiotic thera"y to eradicate enterococci

+ro& the urine be+ore the "rocedure &ay be

reasonable 8Class ((. * B>. + the urinary

tract "rocedure is not elective, it &ay be

reasonable that the e&"iric or s"eci+ic

anti&icrobial rei&en ad&inistered to the

"atient contain an aent active aainst

enterococci 8Class ((. * B>.

A&oicillin or a&"icillin is the "re+erred

aent +or entero7 coccal coverae +or these

"atients. anco&ycin &ay be ad&inistered to

"atients unable to tolerate a&"icillin. + in+ection

is caused by a known or sus"ected strain o+

resistant enterococcus, consultation with an

in+ectious diseases e"ert is reco&&ended.



Table . Summary of 2a3or ,'anges in 4"datedocument

e concluded t'at &acteremia resulting from dailyactiities is muc' more liely to cause #8 t'an&acteremia associated /it' a dental procedure-

e concluded t'at only an e3tremely small num&erof cases of #8 mig't &e preented &y anti&iotic

prop'yla3is een if prop'yla3is is 100" effecti(e- Anti&iotic prop'yla3is is not recommended &asedsolely on an increased lifetime ris of acquisitionof #8-

Eimit recommendations for #8 prop'yla3is only tot'ose conditions listed in

7a&le %-

Anti&iotic prop'yla3is is no longer recommended forany ot'er form of ;<D+ e3cept for t'e conditions

listed in 7a&le %- Anti&iotic prop'yla3is is reasona&le for all dentalprocedures t'at inole manipulation of gingialtissues or periapical region of teet' or perforation of

oral mucosa only for patients /it' underlying cardiacconditions associated /it' t'e 'ig'est ris of

aderse outcome from #8 (7a&le %)-

Anti&iotic prop'yla3is is reasona&le forprocedures on respiratory tract or infected sin+sin structures+ or musculoseletal tissue only for

patients /it' underlying cardiac conditionsassociated /it' t'e 'ig'est ris of aderseoutcome from #8 (7a&le %)-

Anti&iotic prop'yla3is solely to pre(ent #8 is notrecommended for 4 or 4#tract procedures-

Alt'oug' t'ese guidelines recommend c'anges in

indications for #8 prop'yla3is /it' regard to selecteddental procedures (see te3t)+ t'e /riting group

reaffirms t'at t'ose medical procedures listed as notrequiring #8 prop'yla3is in t'e 199 statementremain unc'anged and e3tends t'is ie/ to

aginal deliery+ 'ysterectomy+ and tattooing- Additionally+ t'e committee adises against &odypiercing for patients /it' conditions listed in 7a&le %

&ecause of t'e possi&ility of &acteremia+ /'ilerecogni?ing t'at t'ere are minimal pu&lis'ed dataregarding t'e ris of &acteremia or endocarditisassociated /it' &ody piercing-

Re"imens for Procedures on Infected $kin,

$kin$tructure, or usculoskeletal 2issue

These in+ections are o+ten "oly&icrobial, but

only sta"hylococci and 7he&olytic stre"tococci

are likely to cause . or "atients with the

conditions listed in Table 6 who undero a

surical "rocedure that involves in+ected skin,

skin structure, or &usculo7 skeletal tissue, it &ay

be reasonable that the thera"eutic rei&en

ad&inistered +or treat&ent o+ the in+ection

contain an aent active aainst sta"hylococci

and 7he&olytic stre"tococci, such as an

antista"hylococcal "enicillin or a ce"halos"orin

DTable 8 +or dosae2 Class ((. * C >.

anco&ycin or clinda&ycin &ay be

ad&inistered to "atients unable to tolerate a

7lacta& or who are known or sus"ected to have

an in+ection caused by a &ethicillin7 resistant

strain o+ sta"hylococcus.

A su&&ary o+ the &a@or chanes in these

u"dated reco&7 &endations +or "revention o+

co&"ared with "revious A#A reco&&endations

is shown in Table 4.

$'ecific $ituations and

ircumstances

Patients Alread# Receivin" Anti)iotics

+ a "atient is already receivin lon7ter&

antibiotic thera"y with an antibiotic that is also

reco&&ended +or "ro"hy7 lais +or a dental

"rocedure, it is "rudent to select an antibiotic

+ro& a di++erent class rather than to increase the

dosae o+ the current antibiotic. or ea&"le,antibiotic rei&ens used to "revent the

recurrence o+ acute rheu&atic +ever are

ad&inistered in dosaes lower than those reco&7

&ended +or the "revention o+ . ndividuals

who take an oral




"enicillin +or secondary "revention o+ rheu&atic

+ever or +or other "ur"oses are likely to have

viridans rou" stre"tococci in their oral cavity

that are relatively resistant to "enicillin or

a&oicillin. n such cases, the "rovider should

select either clinda&ycin, azithro&ycin, orclarithro&ycin +or "ro"hy7 lais +or a dental

"rocedure, but only +or "atients shown in Table

6. Because o+ "ossible cross7resistance o+

viridans rou" stre"tococci with ce"halos"orins,

this class o+ antibi7 otics should be avoided. +

"ossible, it would be "re+erable to delay a dental

"rocedure until at least 30 days a+ter co&"le7

tion o+ the antibiotic thera"y. This &ay allow

ti&e +or the usual oral +lora to be reestablished.

Patients receivin "arenteral antibiotic thera"y+or &ay reuire dental "rocedures durin

anti&icrobial thera"y, "articu7 larly i+

subseuent cardiac valve re"lace&ent surery is

antici7 "ated. n these cases, the "arenteral

antibiotic thera"y +or should be continued

and the ti&in o+ the dosae ad@usted to be

ad&inistered 60 to 40 &inutes be+ore the dental

"rocedure. This "arenteral anti&icrobial thera"y

is ad&inistered in such hih doses that the hih

concentration would overco&e any "ossiblelow7level resistance develo"ed a&on &outh

+lora Dunlike the concentration that would occur

a+ter oral ad&inistrationE.

Patients (ho Receive

Anticoa"ulantsntra&uscular in@ections +or "ro"hylaisshould be avoided

in "atients who are receivin anticoaulant

thera"y 8Class ( * %>. n these

circu&stances, orally ad&inistered rei7 &ensshould be iven whenever "ossible.

ntravenously ad&inistered antibiotics should be

used +or "atients who are unable to tolerate or

absorb oral &edications.

Patients (ho 0nder"o ardiac

$ur"er#A care+ul "reo"erative dental evaluation isreco&&ended so that

reuired dental treat&ent &ay be co&"leted

whenever "ossible be+ore cardiac valve sureryor re"lace&ent or re"air o+ !#-. %uch &easures

&ay decrease the incidence o+ late "rosthetic

valve endocarditis caused by viridans rou"

stre"tococci.

Patients who undero surery +or "lace&ent o+

"rosthetic heart valves or "rosthetic intravascular

or intracardiac &ate7 rials are at risk +or the

develo"&ent o+ in+ection.38/

Because the&orbidity and &ortality o+ in+ection in these

"atients are hih, "erio"erative "ro"hylactic

antibiotics are reco&&ended 8Class ( * B>.

arly7onset "rosthetic valve endocarditis is &ost

o+ten caused by S aureus, coaulase7neative

sta"hylo7 cocci, or di"htheroids. (o sinle

antibiotic rei&en is e++ec7 tive aainst all these

&icrooranis&s. Pro"hylais at the ti&e o+

cardiac surery should be directed "ri&arily

aainst sta"hylococci and should be o+ shortduration. A +irst7 eneration ce"halos"orin is

&ost o+ten used, but the choice o+ an antibiotic

should be in+luenced by the antibiotic susce"ti7

bility "atterns at each hos"ital. or ea&"le, a

hih "reva7 lence o+ in+ection by &ethicillin7

resistant S aureus should "ro&"t the

consideration o+ the use o+ vanco&ycin +or

"erio"erative "ro"hylais. The &a@ority o+

nosoco&ial coaulase7neative sta"hylococci

are &ethicillin7resistant. (onetheless, surical "ro"hylais with a +irst7eneration

ce"halos"orin &ay be reco&&ended +or these

"atients 8Class ( * %>.301 n hos"itals with a

hih "revalence o+ &ethicillin7resistant strains o+

S epidermidis, surical "ro"hylais



with vanco&ycin &ay be reasonable but has not

been shown to be su"erior to "ro"hylais with a

ce"halos"orin 8Class ((. * C >. Pro"hylais

should be initiated i&&ediately be+ore the

o"erative "rocedure, re"eated durin "roloned

"rocedures to &aintain seru& concentrations

intrao"eratively, and continued +or no &ore than

9= hours "osto"eratively to &ini&ize e&erence

o+ resistant &icro7 oranis&s 8Class ((a *

B>. The e++ects o+ cardio"ul&onary by"ass and

co&"ro&ised renal +unction on antibiotic

concentra7 tions in seru& should be considered

and dosaes ad@usted as necessary be+ore and

durin the "rocedure.

&ther

onsiderationsThere is no evidence that coronary artery by"assra+t surery is

associated with a lon7ter& risk +or in+ection.There+ore, antibi7 otic "ro"hylais +or dental

"rocedures is not needed +or individ7 uals who

have underone this surery. Antibiotic

"ro"hylais +or dental "rocedures is not

reco&&ended +or "atients with coronary artery

stents 8Class ((( * C >. The treat&ent and

"revention o+ in+ection +or these and other

endovascular ra+ts and "rosthetic devices are

addressed in a se"arate A#A "ubli7 cation.38/

There are insu++icient data to su""ort s"eci+icreco&7 &endations +or "atients who have

underone heart trans"lanta7 tion. %uch "atients

are at risk o+ acuired valvular dys+unction,

es"ecially durin e"isodes o+ re@ection.

ndocarditis that occurs in a heart trans"lant

"atient is associated with a hih risk o+ adverse

outco&e DTable 6E.386 Accordinly, the use o+

"ro"hylais +or dental "rocedures in cardiac

trans"lant reci"ients who develo" cardiac

valvulo"athy is reasonable, but the use+ul7 nessis not well established 8Class ((a * C 2 Table

9E. The use o+ "ro"hylactic antibiotics to "revent

in+ection o+ @oint "rosthe7 ses durin "otentially

bactere&ia7inducin "rocedures is not within the

sco"e o+ this docu&ent.

Future onsiderationsPros"ective "lacebo7controlled, double7blindedstudies o+ anti7

biotic "ro"hylais o+ in "atients who undero

a bactere&ia7 "roducin "rocedure would benecessary to evaluate accurately the e++icacy o+

"ro"hylais. Additional "ros"ective case7

control studies are needed. The A#A has

&ade substantial revisions to "reviously

"ublished uidelines on "ro"hylais. Given

our current reco&&endations, we antici"ate that

sini+i7 cantly +ewer "atients will receive

"ro"hylais +or a dental "rocedure. %tudies are

necessary to &onitor the e++ects, i+ any, o+ these

reco&&ended chanes in "ro"hylais. Theincidence o+ could chane or stay the sa&e.

Because the incidence o+ is low, s&all

chanes in incidence &ay take years to detect.

Accordinly, we ure that such studies be

desined and insti7 tuted "ro&"tly so that any

chane in incidence &ay be detected sooner

rather than later. %ubseuent revisions o+ the

A#A uidelines on the "reven7tion o+ will be

based on the results o+ these studies and other

"ublished data.

Acknowled"ment

sThe writin rou" thanks the +ollowininternational e"erts on in+ec7 tive endocarditis+or their valuable co&&ents5 -rs !hristaGohlke7 BaRrwol+, $oer #all, 'ae7#oon %on,!atherine Kil&artin, !atherine Le"ort, 'oseS M.MiroS , !hristo"h (aber, Graha& $oberts, and'an T.M. van der Meer. The writin rou" alsothanks -r Geore Meyer +or his hel"+ulco&&ents reardin astroenteroloy. inally,the writin rou" would like to thank Lori

#inrichs +or her su"erb assistance with the "re"aration o+ this &anuscri"t.



17/0 Circulation &cto)er 6, 9..

Disclosures

riting *rou" isclosures

Researc'.t'er Researc'

peaersF

@ureau ./ners'ip;onsultant



riting 4roup 8mploym 4r upport <onor #nter Adisory @oard .t

alter ilson $ayo G G Gon Go G G

Earry $- @addour $ayo G G Gon Go G G

Ro&ert 1- @altimore Yale niersity c'ool of $edicine G G Gon Go G G

Ann @olger niersity of ;alifornia+ an *rancisco G G Gon Go G G

Ro&ert .- @ono/ Gort'/estern niersity *ein&erg c'ool of G G Gon Go G G

Hane ;- @urns niersity of ;alifornia+ an Diego G G Gon Go G G

;'ristop'er <-;a&ell

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of <ealt'=

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Patricia *errieri niersity of $innesota $edical c'ool G G Gon Go G G

7imot'y 4ardner ;'ristiana ;are <ealt' ystem G G Gon Go G G

$ic'ael 4er&er ;incinnati ;'ildrenFs <ospital $edical ;enter G G Gon Go G G

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$att'e/ Eeison Dre3el niersity ;ollege of $edicine G G Gon Go $er G

Peter @- Eoc'art ;arolinas $edical ;enter G G Gon Go G G

Hane - Ge/&urger @oston ;'ildrenFs <eart *oundation G G Gon Go G G

7'omas Pallasc' niersity of out'ern ;alifornia Gone

Gone

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;onsultationand e3pert

/itnesstestimony on

records ofpatients /it'

Gone

Anne < - Ro/ley ;'ildrenFs $emorial <ospital+ ;'icago G G Gon Go G G

tanford 7- 'ulman ;'ildrenFs $emorial <ospital+ ;'icago G G Gon Go G G

@rian E- trom niersity of Pennsylania c'ool of$edicine

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Iat'ryn A- 7au&ert American <eart Association G G Gon Go G G

7'is ta&le represents t'e relations'ips of /riting group mem&ers t'at may &e perceied as actual or reasona&ly perceied conflicts of interest as reported on t'eDisclosure Kuestionnaire+ /'ic' all mem&ers of t'e /riting group are required to complete and su&mit- A relations'ip is considered to &e LignificantM if (1) t'e person

receies N10 000 or more during any 1!:mont' period+ or 5" or more of t'e personFs gross incomeC or (!) t'e person o/ns 5" or more of t'e oting stoc or s'ar e oft'e entity or o/ns N10 000 or more of t'e fair maret alue of t'e entity- A relations'ip is considered to &e L$odestM if it is less t'an LignificantM under t'epreceding definition-

$odest-

=ignificant-



(ilson et al Prevention of Infective Endocarditis 17/1

Re&ieer isclosures

Reie/er 8mploymResea

rc'

.t'er

Researc'

peaersF

@urea

83pert

./ners'ip

;onsultant

Adisor

.t

7'omas @as'ore Due niersity $edical ;enter Gone Gone Gone G Gone Gone G

Arnold @ayer niersity of ;alifornia+ Eos

Angeles

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G#<= ;u&ist

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Eairdat $c8lroy+ Deutsc'+$ul(aney J ;arpenter+

Gone Pfi?er G

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$ic'ael *reed @oston ;'ildrenFs <ospital Gone Gone Gone G Gone Gone G

elton 4ersony ;'ildrenFs <ospital of Ge/ Yor Gone Gone Gone G Gone Gone G

Eoren <irat?a @et'esda Gort' <ospital Gone Gone Gone G Gone Gone G

Patric .F4ara @rig'am J omenFs <ospital Gone Gone Gone G Gone Gone G

Eauren E- Patton niersity of Gort' ;arolina Gone Gone Gone G Gone Gone G

;at'erine E- e&& Gort'/estern niersity Gone Gone Gone G Amgen Gone G

7'is ta&le represents t'e relations'ips of reie/ers t'at may &e perceied as actual or reasona&ly perceied conflicts of interest as reported on t'e DisclosureKuestionnaire+ /'ic' all reie/ers are required to complete and su&mit- A relations'ip is considered to &e LignificantM if (1) t'e person receies N10 000 or moreduring any 1!:mont' period+ or 5" or more of t'e personFs gross incomeC or (!) t'e person o/ns 5" or more of t'e oting stoc or s'are of t'e entity or o/ns

N10 000 or more of t'e fair maret alue of t'e entity- A relations'ip is considered to &e L$odestM if it is less t'an LignificantM under t'e preceding definition-$odest-

=ignificant-

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::. Tley@eh M, %teckelber 'M, Murad #%,

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*Oallon WM, Kurland LT.

n+ective endocarditis5 *l&sted !ounty,Minnesota, 3:80 throuh 3:=3.

A!A. 3:=82/89533:: N3/0/.

303. -urack -T, Petersdor+ $G. !hanes in thee"ide&ioloy o+ endocarditis.

Pa"er "resented at5 n+ective ndocarditis5

An A&erican #eart Association

%y&"osiu&2 held May 39 N38, 3:14. n5A#A Monora"h X8/, 3:11.

30/. -elahaye , Goulet , Lacassin , et al.!haracteristics o+ in+ective endo7 carditis in

rance in 3::35 a 37year survey. #ur &eart .

3::823456:9 N 903.

306. #oen B, Alla , %elton7%uty !, Beuinot ,

Bouvet A, Briancon %, !asalta 'P, -anchin

(, -elahaye , tienne ', Le Moin ,

Le"ort !, Mainardi 'L, $ui&y $,

andenesch 2 Association "our lOtude et la

Prevention de lOndocardite n+ectieuse

DAPE %tudy Grou".

!hanin "ro+ile o+ in+ective endocarditis5

results o+ a 37year survey in

rance. A!A. /00/2/==518N =3.

309. Mylonakis , !alderwood %B. n+ective

endocarditis in adults. " #ngl

!ed . /00326985363= N3660.

308. Gersony WM, #ayes !', -riscoll -',

Keane ', Kidd L, *Oallon WM, Pieroni

-$, Wol+e $$, Weid&an W#. Bacterialendocarditis in "atients with aortic stenosis,

"ul&onary stenosis, or ventricular se"tal

de+ect. Circulation. 3::62=1Dsu""lE573/3N7

3/4.

304. Wilson W$, 'au&in PM, -anielson GK,

Giuliani $, Washinton 'A , Geraci '.

Prosthetic valve endocarditis. Ann Intern

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301. Baddour LM, Wilson W$. n+ections o+

"rosthetic valves and other cardio7 vasculardevices. n5 Mandell GL, Bennett ', -olin

$, eds. !andell, Douglas, and 'ennett3s

Principles and Practice of Infectious

Diseases. Philadel"hia, Pa5 lsevier

!hurchill Livinstone2 /008530//N3099.

30=. Baddour LM, Wilson W$, Bayer A%,

owler G 'r, Boler A, Levison M,

errieri P, Gerber MA, Tani L), Gewitz M#,

Ton -!, %teckelber 'M, Balti&ore $%,

%hul&an %T, Burns '!, alace -A, (ewburer 'W, Pallasch T', Takahashi M,

Taubert KA2 !o&&ittee on $heu&atic

ever, ndocarditis, and Kawasaki -isease2

!ouncil on !ardiovascular -isease in the

)oun2 !ouncils on !linical !ardioloy,

%troke, and !ardiovascular %urery and

Anesthesia2 A&erican #eart Association2

n+ectious -iseases %ociety o+ A&erica.

n+ective endo7 carditis5 dianosis,

anti&icrobial thera"y, and &anae&ent o+co&"li7 cations5 a state&ent +or healthcare

"ro+essionals +ro& the !o&&ittee on

$heu&atic ever, ndocarditis, and

Kawasaki -isease, !ouncil on !ar7

diovascular -isease in the )oun, and the

!ouncils on !linical !ar7 dioloy, %troke,

and !ardiovascular %urery and Anesthesia,

A&erican #eart Association5 endorsed by the

n+ectious -iseases %ociety o+ A&erica

U"ublished correction a""ears in Circulation./008233/5/616V. Circulation. /00823335e6:9

N e969.



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stre"to&ycin +or in+ective endocarditis due

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Miro 'M, #oen B, %elton7%uty !, -oco7

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"ros7 thetic valve in+ective endocarditis5

re"ort o+ 98 e"isodes +ro& the nter7 national

!ollaboration on ndocarditis7&ered

database. #ur Clin !icrobiol Infect Dis.

/0082/95448N 410.33/. !hu #, !abell !#, Abrutyn , !orey

G$, #oen B, Miro 'M, *laison L,

%try@ewski M, Pa""as P, Anstro& K',

ykyn %, #abib G, Benito (, owler G 'r2

nternational !ollaboration on ndocarditis

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sta"hylococci5 re"ort o+ :: e"isodes +ro& the

nternational !ollaboration on ndocarditis

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336. Lalani T, Kana+ani A, !hu #, Moore L,

!orey G$, Pa""as P, Woods !W, !abell !#,

#oen B, %elton7%uty !, -oco7Leco&"te T,

!hirouze !, $aoult -, Miro 'M, Mestres

!A, *laison L, ykyn %, Abrutyn , owler

G 'r2 The nternational !ollaboration on

ndocarditis Mered -atabase %tudy Grou".

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coaulase7neative sta"h7 ylococci5 +indins

+ro& the nternational !ollaboration on

ndocarditis Mered -atabase. #ur Clin

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339. Mc-onald '$, *laison L, Anderson -',

#oen B, Miro 'M, ykyn %, Abrutyn ,

owler G 'r, #abib G, %elton7%uty !,

Pa""as PA, !abell !#, !orey G$, Marco ,

%eton -'. nterococcal endocarditis5 301

cases +ro& the nternational !ollaboration on

ndocarditis Mered -atabase. Am !ed .

/008233=518: N144.

338. %eton -', Tenenbau& M', Wilson W$,

%teckelber 'M, Tice A-, Gilbert -,

-is&ukes W, -rew $#, -urack -T2

ndocarditis Treat&ent !onsortiu& Grou".

!e+triaone once daily +or +our weeks

co&"ared with ce+triaone "lus enta&icin

once daily +or two weeks +or treat&ent o+endocarditis due to "enicillin7susce"tible

stre"tococci. Clin Infect Dis. 3::=2/153910 N

3919.

334. rancioli P, tienne ', #oine $, Thys 'P,

Gerber A. Treat&ent o+ stre"tococcal

endocarditis with a sinle daily dose o+

ce+triaone sodiu& +or 9 weeks5 e++icacy and

out"atient treat&ent +easibility. A!A. 3::/2

/415/49 N/41.

331. Wilson W$, Wilkowske !', Wriht A',%ande MA, Geraci '.

Treat&ent o+ stre"to&ycin7susce"tible and

stre"to&ycin7resistant enterococcal

endocarditis. Ann Intern !ed . 3:=923005=34

N =/6.

33=. Mansur A', -al Bo !M, ukushi&a 'T,

ssa %, Grinber M, Po&er7 antze++ PM.

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and &ortality



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$uo++ KL. &erence o+ hih rates o+

anti&icrobial resistance a&on viridans

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"atients with and without the dianosis o+

cancer in the <%A, !anada and Latin

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381.

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M, Meechan 'G. Anti&icrobial resistance

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stre"tococci strains +ro& hih7risk

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N 936.

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Luk KT. Anti&icrobial susce"7 tibility o+

viridans rou" stre"tococci in Taiwan with

an e&"hasis on the hih rates o+ resistance to

"enicillin and &acrolides in Streptococcus

oralis. Antimicrob Chemother .

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susce"tibility o+ viridans rou"

stre"tococci. Diagn !icrobiol Infect Dis.

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'arvinen #, 'alava ', #uovinen P.

Anti&icrobial susce"tibility "atterns and

&acrolide resistance enes o+ viridans rou"

stre"tococci +ro& nor&al +lora. Antimicrob

Che$ mother . /00628/5464 N 499.

39/. Marron A, !arratala ', Alcaide ,ernandez7%evilla A, Gudiol . #ih rates o+

resistance to ce"halos"orins a&on viridans7

rou" stre"tococci causin bacterae&ia in

neutro"enic cancer "atients. Antimicrob

Che$ mother . /0032915=1N:3.

396. Wu '', Lin K), #sueh P$, Liu 'W, Pan #,

%heu %M. #ih incidence o+ erythro&ycin7

resistant stre"tococci in Taiwan. Antimicrob

Agents Chemother . 3::12935=99 N =94.

399. Kin A, Bathate T, Philli"s .rythro&ycin susce"tibility o+ viridans

stre"tococci +ro& the nor&al throat +lora o+

"atients treated with azithro&ycin or

clarithro&ycin. Clin !icrobiol Infect .

/00/2=5=8N:/.

398. %tro& BL, Abrutyn , Berlin 'A, Kin&an

'L, eld&an $%, %tolley P-, Levison M,

Korzeniowski *M, Kaye -. $isk +actors +or

in+ective endocarditis5 oral hyiene and

nondental e"osures. Circulation. /000230/5/=9/N/=9=.

394. ridkin %K, Gaynes $P. Anti&icrobial



resistance in intensive care units.

Clin Chest !ed . 3:::2/05606N634, viii.

391. %hay -K, Maloney %A, Montecalvo M,

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risk o+ vanco&ycin7resistant enterococcal

bloodstrea& in+ections. Infect Dis.

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outco&e o+ "atients with bactere&ia caused

by Staph$ ylococcus aureus. Arch Intern

!ed . 3::=238=53=/N3=:.

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$enier B, !hevret %. Attrib7 utable

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se"tice&ia in critically ill "atients5 a

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&icrobial susce"tibility o+ isolates collected

in 3::1 in the <nited %tates, !anada, and

Latin A&erica +ro& the %(T$)

Anti&icrobial %ur7 veillance Prora&.

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38/. Baddour LM, Bett&ann MA, Boler A,

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M#, 'acobs AK, Levison M, (ewburer

'W, Pallasch T', Wilson W$, Balti&ore $%,

alace -A, %hul&an %T, Tani L), Taubert

KA2 A&erican #eart Association.

(onvalvular cardiovascular device7 related

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/063.386. %her&an7Weber %, Aelrod P, %uh B,

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n+ective endocarditis +ollowin orthoto"ic

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/009245348N310.



orrection

n the A#A Guideline by Wilson et al, Prevention o+ n+ective ndocarditis5

Guidelines ro& the A&erican #eart Association5 A Guideline ro& the

A&erican #eart Association $heu&atic ever, ndocarditis, and Kawasaki

-isease !o&&ittee, !ouncil on !ardiovascular -isease in the )oun, and the!ouncil on !linical !ardioloy, !ouncil on !ardiovascular %urery and

Anesthesia, and the Cuality o+ !are and *utco&es $esearch nterdisci"linary

Workin Grou", that "ublished online on A"ril 3:, /001 D-*5

30.3343;!$!<LAT*(A#A.304.3=60:8E, several chanes are needed.

A+ter online "ublication o+ these uidelines, the writin rou" was &ade

aware that there was con+usion a&on the readershi" reardin the use o+ the

lanuae $eco&&ended in the title o+ Tables 6 and 9 and &ay be

reasonable or &ay be considered in the tet when re+errin to our !lass

b reco&&endations. The writin rou" has clari+ied this by revisin the

wordin in the tables and chanin the lanuae in the tet to isreasonable. Accordin to eistin A&erican #eart Association "olicy +or

wordin o+ classes o+ reco&&en7 dations, this chane in lanuae is

acco&"anied by a shi+t in the class o+ reco&&endation +ro& b to a as

detailed in the errata.

3. %ince the online "ublication o+ this article, the A&erican Acade&y o+

Pediatrics and the nternational %ociety o+ !he&othera"y +or n+ection

and !ancerH have added their endorse&ents.

/. *n "ae 3164, in the +ootnotes section, the +ollowin +ootnote a""lies to

the endorse&ent by the nternational %ociety o+ !he&othera"y +orn+ection and !ancer5 H+ these uidelines are a""lied outside o+ the

<nited %tates o+ A&erica, ada"tation o+ the reco&&ended antibiotic

aents &ay be considered with res"ect to the reional situation.

6. *n "ae 3161, in the !onclusions "art o+ the abstract, the

+ollowin ite&s have been &odi+ied5 D/E n+ective endocarditis

"ro"hylais +or dental "rocedures is reasonable only +or "atients with

underlyin cardiac conditions associated with the hihest risk o+ adverse

outco&e +ro& in+ective endocarditis. D6E or "atients with these

underlyin cardiac condi7 tions, "ro"hylais is reasonable +or all dental

"rocedures that involve &ani"ulation o+ inival tissue or the "eria"icalreion o+ teeth or "er+oration o+ the oral &ucosa.

9. n Table 6 on "ae 3198, the +ollowin ite&s have been &odi+ied5

a. The title now reads5 !ardiac !onditions Associated With the #ihest

$isk o+ Adverse *utco&e ro& ndocarditis +or Which Pro"hylais

With -ental Procedures s $easonable

b. The +irst entry now reads5 Prosthetic cardiac valve or "rosthetic

&aterial used +or cardiac valve re"air

c. The second +ootnote now reads5 QPro"hylais is reasonable because

endothelialization o+ "rosthetic &aterial occurs within 4 &onths a+terthe "rocedure.

8. *n "ae 3198, second colu&n, second "arara"h, the +i+th sentence has



orrection e377

:. *n "ae 3194, +irst colu&n, +ourth "arara"h, the +ourth and +i+th

sentences have been &odi+ied to read5 There+ore, antibiotic "ro"hylais

is reasonable +or "atients with the conditions listed in Table 6 who

undero any dental "rocedure that involves the inival tissues or

"eria"ical reion o+ a tooth and +or those "rocedures that "er+orate the

oral &ucosa DTable 9E. Althouh "ro"hylais is reasonable +or these "atients, its e++ectiveness is unknown 8Class ((a * C E.

30. or Table 9 on "ae 3194, the title has been chaned to5 -ental Procedures +orWhich

ndocarditis Pro"hylais s $easonable +or Patients in Table 6.

33. *n "ae 3191, second colu&n, under the $ei&ens +or $es"iratory

Tract Procedures headin, the second sentence has been &odi+ied to

read5 Antibiotic "ro"hylais with a rei&en listed in Table 8 is

reasonable 8Class ((a * C E +or "atients with the conditions listed in

Table 6 who undero an invasive "rocedure o+ the res"iratory tract that

involves incision or bio"sy o+ the res"iratory &ucosa, such astonsillecto&y and adenoidecto&y.

3/. n Table 4 on "ae 319=, the +ollowin ite&s have been u"dated5

a. The sith entry should read5 Antibiotic "ro"hylais is

reasonable +or all dental "rocedures that involve &ani"ulation o+

inival tissues. . . .

b. The seventh entry should read5 Antibiotic "ro"hylais is reasonable

+or "rocedures on res"iratory tract or in+ected skin, skin structures, or

&usculoskeletal. . ..

c. The last entry should read5 Althouh these uidelines reco&&end

chanes in indications +or "ro"hylais with reard to selected dental

"rocedures Dsee tetE, the writin rou" rea++ir&s that those &edical

"rocedures listed as not reuirin "ro"hylais in the 3::1 state&ent

re&ain unchaned and etends this view to vainal delivery and

hysterecto&y and tattooin. Additionally, the co&&ittee advises

aainst body "iercin +or "atients in Table 6 because o+ the "ossibility

o+ bactere&ia, while reconizin there are &ini&al "ublished data

reardin the risk o+ bactere&ia or endocarditis associated with body

"iercin.

36. *n "ae 319=, second colu&n, the headin at the to" o+ the colu&n has

been &odi+ied to read5 $ei&ens +or Procedures on n+ected %kin, %kin

%tructure, or Musculoskeletal Tissue.

39. *n "ae 319=, second colu&n, +irst "arara"h, the second sentence has

been &odi+ied to read5 or "atients with the conditions listed in Table 6

who undero a surical "rocedure that involves in+ected skin, skin

structure, or &usculoskeletal tissue, it &ay be reasonable that the

thera"eutic rei&en ad&inistered +or treat&ent o+ the in+ection contain an

aent active aainst sta"hylococci. . . .

38. *n "ae 319:, +irst colu&n, last "arara"h, the last sentence has been

&odi+ied to read5 n hos"itals with a hih "revalence o+ &ethicillin7

resistant strains o+ S epidermidis, surical "ro"hylais with vanco&ycin

&ay be reasonable but has not been shown to be su"erior to "ro"hylais. .

..



34. *n "ae 319:, second colu&n, under the headin *ther

!onsiderations, the "enulti&ate sentence has been &odi+ied to read5

Accordinly, the use o+ "ro"hylais +or dental "rocedures in cardiac

trans"lant reci"ients who develo" cardiac valvulo"athy is reasonable, but

the use+ulness is not well established DClass ((a * C 2 Table 9E.

These chanes have been &ade in the current "rint DCirculation.

/001233453164 N3189E and online versions o+ the article.

D&I: -.+--/-*IR01A2I&3AHA+-.+-47766





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