DOI: 10.1161/CIRCULATIONAHA.112.115204
Antibiotic Prophylaxis for Dental Procedures: Are We Drilling in
the Wrong Direction?
Running title: Lockhart; Antibiotic prophylaxis for dental procedures
Downloaded from http://circ.ahajournals.org/ by guest on June 16, 2017
Peter B. Lockhart, DDS
Carolinas Medical Center, Charlotte, NC
Add
Ad
dr forr Correspondence:
dress
C rr
Co
rresp
ponden
en
ncee:
Address
Pete
er B
Loc
ockhhar
a t, D
DDS
DS
Peter
B.. L
Lockhart,
Professor and
an
nd Ch
Chai
airr
ai
Chair
Department of Oral Medicine
Carolinas Medical Center
P.O. Box 32861
Charlotte, NC 28232-2861
Tel: 704-355-1709
Fax: 704-355-5301
E-mail: [email protected]
Journal Subject Code: [111] Infectious endocarditis
Key words: cardiovascular diseases; echocardiography; Editorials; heart diseases
1
DOI: 10.1161/CIRCULATIONAHA.112.115204
The possibility that bacteremia from the mouth could cause infective endocarditis (IE) was first
suggested over a hundred years ago, and it was later reinforced by others who targeted the
viridans group streptococcus (VGS) from poor oral hygiene and dental extractions.1-3 These
observations, along with the advent of antibiotics, eventually led to the first guidelines from the
American Heart Association (AHA) in 1955. Antibiotic prophylaxis (AP) became the primary
focus for prevention of IE, and a standard of care for countries around the world. Controversy
concerning efficacy and safety issues has existed for over 30 yeas and there has been a
progressive reduction in the patient populations and the procedures suggested for AP since that
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time. Of concern, and in spite of a decreasing emphasis on AP for cardiac patients, upwards of
utt off cconcern
once
on
cern
ce
rn
25 non-cardiac patient populations are recommended for AP by some clinicians oout
for systemic infections that might originate from dental procedures (e.g., prosthetic joints).4
S
Significant
igni
ig
nifficaant differences
ni
d
in recommendations
recommendatio
ons
n from experts in
i the
hee U.S.,
U
United Kingdom,
and
an
nd other
other countries
coun
ntr
trie
iess over
ovverr the
the years
years
ears highlight
hhiighhliight the
th
he lack
laack
k off convincing
convinci
con
cing
ng data
dat
ataa to
to either
eith
ei
ther
th
er support
sup
uppo
po
ortt or
or reject
reject
rej
this
issued
his practice.
ppra
ract
ra
ctic
icce. The
Thee National
Nat
atiionnal
nal Institute
Innst
stit
itut
it
utee for
ut
for Health
Heal
He
alth
al
h and
aannd Clinical
Clinic
inic
ical
al Excellence
Exc
E
x elle
xc
leenc
n e (NICE)
(N
NIC
CE) in
in the
th
he U.K.
U.K
K. iiss
K.
ssuued
new recomm
recommendations
men
enda
d ti
da
tion
o s in
on
i 22006,
006,
00
6, w
which
hiich
c ttook
ookk th
oo
thee bo
bold
old step
s ep
st
p of
of eliminating
elim
el
imin
im
i at
atin
in
ng AP aall
lll ttog
together.
oget
og
e he
et
h r.5 Curren
Current
n
(2007) AHA guidelines narrow the focus to only four cardiac groups at “higher” risk for a “bad
outcome” from IE, but who represent approximately 10% of all people at risk for IE.6 The AHAdefined “moderate” risk groups represent approximately 90% of people at risk for IE, all of
whom were recommended for AP prior to 2007. There are, therefore, no preventive guidelines
for the millions of people in the U.S. at risk for contracting IE but who are not felt to benefit
from AP.7
Although there is understandable concern on the part of some cardiologists and some
patients about eliminating AP, a recent retrospective study by Thornhill et al suggests that AP
2
DOI: 10.1161/CIRCULATIONAHA.112.115204
has no significant impact on the incidence of, or death from IE.8 The authors point out that these
findings may not apply to patients in the higher risk groups since approximately 20% of
physicians in the U.K. may continue to use AP in spite of NICE guidelines that mandate a
cessation for this practice, unless the patient requests it. This group did find a modest increase in
the incidence of IE over their 10 year period due to both streptococci and staphylococci.
Support for the role of oral bacteria as a significant cause of IE comes largely from two
sources. The best evidence for this association is the frequency with which specifically oral
bacterial species are cultured from the blood of patients with community-associated (CA-IE).
Downloaded from http://circ.ahajournals.org/ by guest on June 16, 2017
The literature suggests that 20% to 65% of cases of IE worldwide result from bacteria that can be
attribut
uteed
ed to
t oral
oral
found in, or are exclusive to the mouth.7, 9 This wide range of cases of IE attributed
bacteria stems, in part, from the use of standard biochemical rather than molecular methods of
bacterial
ba
act
cter
eria
er
iall id
ia
iden
identification.
entifi
en
fica
cati
ca
tion.10 For example, reports of V
VGS are not sp
specific
pec
e ific
ic en
eenough
nough to implicate the
mouth
m
ouuth
ut as the source.
souurcce. Other
Oth
O
th
her supporting
ssup
uppo
up
port
r in
rt
ingg ddocumentation
ocu
ume
m ntaatiion co
comes
omees fr
fro
from
om oover
om
verr 75
ve
75 yyears
ears ooff ba
ears
bac
bacteremia
cterem
erem
miaa
studies
procedures
other
manipulations
tissues.
tud
udie
iees of ddental
enta
en
tall pr
roc
oceedur
edur
u es aand
nd oot
the
h r ma
mani
nipu
ni
pula
pu
lati
la
tion
on
ns of
of ggingival
ingiiva
in
v l ti
iss
ssue
uees.3 T
These
h se
he
s studies
stu
tuddie
dies suggest
sug
uggges
gest a
wide range ooff in
inci
ciide
denc
ncce off bbac
a teere
remi
m a fr
mi
ffrom
om sspecies
pec
e ie
iess kn
kknown
ownn to ccause
ow
ause
au
see IIE,
E, aand
nd oone
ne m
mus
ustt conclude
us
incidence
bacteremia
must
that oral bacteremia is likely to occur with the vast majority of dental office visits. These studies
employ surrogate measures of risk for IE (i.e., incidence, duration, nature, and magnitude of
bacteremia) but they have driven the focus on AP for dental procedures since the 1950’s.
Retrospective case-control studies provide a closer look at this relationship. Strom et al
contacted patients who had been hospitalized (cases) for IE at one of 54 hospitals in the
Philadelphia area and compared them with matched community residents (controls). 11 His
group found that recent dental treatment was no more frequent in cases than in controls, and they
concluded that dental treatment did not seem to be a risk factor for CA-IE. The study by
3
DOI: 10.1161/CIRCULATIONAHA.112.115204
DeSimone et al in this issue of Circulation moves us one step closer to a better understanding of
this question of efficacy for AP by conducting the first population-based study in the U.S. to
determine the impact of the 2007 AHA guidelines.12 They focused on cases of IE from presumed
oral streptococci over a 12 year period, and found no increase in VGS IE in the two plus years
since 2007. Of interest, two of the three patients who developed IE from VGS after 2007 had not
been to the dentist in the previous six months, and the third patient had AP prior to a recent
dental office procedure.
Case-control, population-based, and other epidemiologic investigations often have
Downloaded from http://circ.ahajournals.org/ by guest on June 16, 2017
methodological weaknesses that soften their impact, for example: i) small sample size and
power; ii) subject recall bias; iii) demographics that may not be representative off the
hee ggeneral
ener
en
eral
er
al
population; iv) incubation time frames that are too long for IE; v) the imperfect nature of hospita
hospital
an
nd national
nati
na
tion
ti
onnal data
ddatta bases
ba on admission and discharge
dischaarg
rgee coding; and, IICD-9
CD--9 ccoding
CD
oding of bacterial
and
peccie
i s. Neve
ert
rthe
h less
he
sss, results
resu
re
s ltts from
su
from
m well-designed
welll-dessiggnedd sstudies
tuddiees are
aree im
mpoort
rtan
an
nt because
becau
bec
cause
use they
they provide
pro
ovi
vidde
species.
Nevertheless,
important
additional
ad
ddi
d ti
tion
o al evidence
on
evi
vide
denc
ncee th
nc
that
hat tthe
h w
he
well
elll in
el
inte
intentioned
tennti
t on
oned
ed ffocus
o us
oc
us oon
n AP m
may
ay bbee mi
misd
misdirected.
sddirrec
ecte
teed.
The A
HA,, In
HA
Inst
sttittut
u e of M
e iccin
ed
ine,
e, N
ICE
IC
E an
nd ot
oother
heer pr
prof
ofes
of
essi
es
s onnal ggro
si
roup
ro
upss ha
up
have
ve ccalled
a led for
al
AHA,
Institute
Medicine,
NICE
and
professional
groups
studies that would resolve this longstanding question concerning the efficacy of AP, and clarify
the role of poor oral hygiene and resulting periodontal disease in the pathogenesis of IE. 5, 6, 13
Although there have been calls for a prospective, randomized, double blind study of AP in
people at risk for CA-IE, significant obstacles exist, for example: i) there are ethical and legal
concerns about randomizing people in the AHA higher risk group to a placebo; ii) such a trial
would only address the 10% of people currently recommended for AP in the U.S.; and, iii) given
the rarity of IE, it has been estimated that upwards of 30,000 people at risk would be needed to
detect a clinically important AP treatment effect, and the cost of this trial would be prohibitive.
4
DOI: 10.1161/CIRCULATIONAHA.112.115204
Transient bacteremia frequently occurs as a result of dental plaque accumulation,
evolving to a dense mat of oral bacteria around the teeth which cross the inflamed periodontal
pocket tissues to the circulation. Clearly, this must be the main source and portal of entry for the
oral bacterial species that cause upwards of 25% of cases of CA-IE. Current science strongly
suggests that poor oral hygiene and periodontal disease are far greater risk factors for the
development of oral bacteria-related IE than invasive dental procedures. The largest study to date
compared tooth extraction, a highly invasive dental procedure, with tooth brushing as a common,
naturally-occurring source of bacteremia.14, 15 This group found that the incidence of bacteremia
Downloaded from http://circ.ahajournals.org/ by guest on June 16, 2017
from tooth brushing (32%) was high enough to strongly suggest that bacteremia from various
activities of daily living (chewing food as well) may occur hundreds of times mo
more
ore of
often
fte
tenn th
than
a
an
bacteremia from dental office procedures. Indeed, it has been suggested that some individuals
may
may ge
gene
generate
nera
rate
ra
te bbacteremia
accte
terremia for 90 hours each mont
month
nthh ffrom
nt
rom such “phy
“physiologic”
hyysiollog
ogic
ic” causes,16 by
co
comparison
omparison
mp
w
with
ithh ddental
it
ent
ntal
a ooffice
ffic
ff
icee pr
ic
proc
procedure-generated
occedu
eduree-gene
nerateed ba
ne
bacteremia
act
cter
erem
em
mia ooff on
onee to two
wo ttimes
imees pper
im
er yyear
ear onn
ear
average.
This
study
provides
documentation
three
oral
av
ver
erag
age.
ag
e T
e.
Thi
hiss st
hi
stu
udy pr
udy
rov
vid
idess uunique
niqu
ni
quee do
qu
ocu
cume
ment
me
ntat
nt
a io
at
on off a str
sstrong
tron
tr
on
ng aassociation
sssoc
ocia
iaatiion
on bbetween
ettwe
weeen th
hre
reee or
rall
hygiene and gingival
ging
gi
ngiv
ng
ival
iv
a disease
al
disseaase parameters
par
araame
mete
ters
rs aand
nd tthe
h iincidence
he
ncid
nc
i en
id
nce ooff ba
bact
bacteremia
c er
erem
emia
em
ia w
with
i h IE
it
IE-related
E-rrel
elat
a ed
species.17 These associations strengthened with higher levels of dental plaque and calculus and
gingival disease.
DeSimone and colleagues have provided further data to reinforce the trend towards a
greatly decreased number of cardiac patients recommended for AP, as well as support for a more
definitive study to determine the extent to which oral hygiene, periodontal disease and oral
bacteria are associated with CA-IE. These data would improve our understanding of risk factors,
and re-focus efforts on prevention of IE to improving oral hygiene and preventing periodontal
disease. This information has the potential to reduce the overall incidence of CA-IE, it would be
5
DOI: 10.1161/CIRCULATIONAHA.112.115204
immediately transferable to everyday clinical practice, and it would inform future AHA and
other international guidelines on preventive strategies for IE.
Conflict of Interest Disclosures: None.
References:
1. Horder TJ. Infective endocarditis with an analysis of 150 cases and with special reference to
the chronic form of the disease. Q J Med. 1909;2:289-324.
2. Thayer W. Studies on bacterial (infective) endocarditis. Hopkins Hosp Rep. 1926;22:1-185.
Downloaded from http://circ.ahajournals.org/ by guest on June 16, 2017
3. Okell CC, Elliott SD. Bacteriæmia and oral sepsis with special reference to the ætiology of
subacute endocarditis. Lancet. 1935;2:869-872.
;
efficacy
antibiotic
4. Lockhart PB, Loven B, Brennan MT, Fox PC. The evidence base for the effica
acy ooff an
anti
tibi
ti
biot
otic
ot
ic
prophylaxis in dental practice. J Am Dent Assoc. 2007;138:458-474.
Team.
5. NICE
NIC
CE Short
Shor
Sh
ort Clinical
or
Cllin
inic
i al Guidelines Technical Te
eam
am.. Prophylaxis against
agaiins
nstt infective endocarditis:
antimicrobial
prophylaxis
against
infective
an
nti
tim
mic ob
micr
bia
iall pr
rop
ophy
hylaxi
xiss ag
agai
ains
n t in
infe
fectiv
i e endocarditis
en
ndo
doccar
carditiss in
in adults
adult
ltss and
and children
ch en uundergoing
nderrgo
goin
ng
interventional
London:
and
Clinical
Excellence;
nteerv
rvention
nal pprocedures.
roccedu
cedu
dure
rees. Lo
Lond
ndon
nd
on:: National
on
Nati
Na
tion
ti
onnal Institute
IIns
n tiitu
ute for
for Health
Hea
H
e ltth an
ea
nd Cl
iniccal E
in
Exc
xcel
xc
elle
el
leence;
nce; 22008.
0088.
00
6. Wilson
Wil
W
i so
son W, Taubert
Taaubert
T
bert KA,
KA, Gewitz
Gew
wit
itz M,
M Lockhart
Loc
ockh
khhart
ar PB,
PB, Baddour
Badddo
Ba
ddour LM,
LM
M, Levison
Levvisson M,
M, Bolger
Bol
B
ollger
ge A, Cabell
Caabeell
C
Takahashi
Baltimore
RS,
Newburger
JW,
Strom
Gerber
Bonow
RO,
CH,, Ta
CH
Taka
kaha
ka
hash
ha
shii M,
M B
alti
al
tim
ti
mo e R
more
RS
S, N
S,
New
ewbu
burg
bu
rger
rg
er JJW
W, St
Stro
rom
m BL
BL, Tani
Tani L
LY,
Y G
Y,
Ger
e be
er
berr M,
M B
Bon
onow
on
ow R
O,
O,
Pallasch
Pall
Pa
llas
ll
asch
as
ch TJ,
TJJ, Shulman
T
Shu
S
hulm
hu
lman
lm
an ST,
ST
S
T, Rowley
Row
R
owle
ow
leyy AH,
le
AH Burns
Burn
Bu
rnss JC,
rn
JC Ferrieri
Ferr
Fe
rrie
rr
ieri
ie
ri P,
P Gardner
Gard
Ga
rdne
rd
nerr T,
ne
T, Goff
G
Gof
offf D,
of
D, Durack
D
Dur
urac
ur
ackk DT.
ac
DT
infective
guidelines
American
Heart
Association.
Prevention ooff in
infe
fect
fe
ctiv
ct
ivee endo
iv
eendocarditis.
ndo
doca
card
rd
dit
itis
iss. gu
uid
idel
elin
el
inees fr
in
from
om tthe
he A
Ame
meri
me
rica
ri
c n He
Hear
artt As
ar
A
soociiat
a io
ionn. a
guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki
Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on
Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care
and Outcomes Research Interdisciplinary Working Group. Circulation. 2007;116:1736-1754.
7. Mylonakis E, Calderwood SB. Infective endocarditis in adults. N Engl J Med. 2001;345:13181330.
8. Thornhill MH, Dayer MJ, Forde JM, Corey GR, Chu VH, Couper DJ, Lockhart PB. Impact of
the NICE guideline recommending cessation of antibiotic prophylaxis for prevention of infective
endocarditis: before and after study. BMJ. 2011;342:d2392.
9. Tleyjeh IM, Steckelberg JM, Murad HS, Anavekar NS, Ghomrawi HM, Mirzoyev Z,
Moustafa SE, Hoskin TL, Mandrekar JN, Wilson WR, Baddour LM. Temporal trends in
infective endocarditis: a population-based study in Olmsted County, Minnesota. JAMA.
2005;293:3022-3028.
6
DOI: 10.1161/CIRCULATIONAHA.112.115204
10. Bahrani-Mougeot FK, Paster BJ, Coleman S, Ashar J, Knost S, Sautter RL, Lockhart PB.
Identification of oral bacteria in blood cultures by conventional versus molecular methods. Oral
Surg Oral Med Oral Pathol Oral Radiol Endod. 2008;105:720-724.
11. Strom BL, Abrutyn E, Berlin JA, Kinman JL, Feldman RS, Stolley PD, Levison ME,
Korzeniowski OM, Kaye D. Dental and cardiac risk factors for infective endocarditis: a
population-based case-control study. Ann Intern Med. 1998;129:761-769.
12. DeSimone D.C., Tleyjeh IM, Correa de Sa DD et al. Incidence of infective endocarditis due
to viridans group Streptococci before and after publication of the 2007 American Heart
Association's endocarditis prevention guidelines. Circulation. 2012;126:XXX-XXX.
13. Institute of Medicine CoMCE. Medically necessary dental services. In: Field MJ, Lawrence
RL, Zwanziger L, editors. Extending Medicare Coverage for Preventive and Other Services.
Washington, D.C.: National Academy Press; 2000. p. 63-98.
Downloaded from http://circ.ahajournals.org/ by guest on June 16, 2017
14. Lockhart PB, Brennan MT, Sasser HC, Fox PC, Paster BJ, Bahrani-Mougeot FK. Bacteremia
associated with toothbrushing and dental extraction. Circulation. 2008;117:3118-3125.
2008;117:3118-3
312
125.
5.
PB.
Diverse
15. Bahrani-Mougeot FK, Paster BJ, Coleman S, Ashar J, Barbuto S, Lockhart P
B D
B.
Div
iver
erse
er
se aand
nd
novel oral bacterial species in blood following dental procedures. J Clin Microbiol.
2008;46:2129-2132.
2008;4
; 6:2129
9-2132.
16.
WG.
How
important
dental
endocarditis?
16
6. Guntheroth
Gu
Gunthero
rooth
t W
G. H
ow iimp
mp
por
orta
tant
ta
nt ar
aree de
dent
ntal
al pprocedures
rocedu
ure
ress as
a a ccause
au
use ooff in
iinfective
fect
fe
cttiv
ivee en
endo
doca
card
ca
rd
dit
itis
i?
is
Am
A
m J Cardiol. 1984;54:797-801.
198
9 4;
4;54
5 :7
54
797
97-8
-8
801
01..
17.
Lockhart
BS,
Bahrani-Mougeot
FK,
17
7. Lo
Lock
c haart PB,
ck
P
PB
B, Brennan
B,
Bre
renn
nnan
a MT,
an
MT, Thornhill
Tho
T
horn
ho
rnh
hill M,
hill
M Michalowicz
Micha
Mic
chalow
alow
wic
iczz BS
S, No
Noll
ll JJ,, Ba
ahrran
a ii Mo
Mouuge
ugeott FK
K,
Sasser
HC.
Poor
infective
bacteremia.
Sass
ser H
C. Poo
oorr or
oral
al hhygiene
ygie
ienee aass a risk ffactor
acto
ac
torr ffor
or infec
ecti
tive
ve eendocarditis-related
ndoocar
nd
ardi
diti
tiss reela
lateed ba
bacter
erem
emia
ia. J Am
m
Dent Assoc. 2009;140:1238-1244.
200
009;
9;14
9;
140:
14
0:12
1 38
12
8-1
124
44.
4
7
Antibiotic Prophylaxis for Dental Procedures: Are We Drilling in the Wrong Direction?
Peter B. Lockhart
Circulation. published online June 11, 2012;
Downloaded from http://circ.ahajournals.org/ by guest on June 16, 2017
Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 2012 American Heart Association, Inc. All rights reserved.
Print ISSN: 0009-7322. Online ISSN: 1524-4539
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