Richard Stutt Nik Cunniffe Erik DeSimone Matt Castle Chris Gilligan February 2012.
Incidence of Infective Endocarditis due to Viridans Group ...€¦ · 11/6/2012 · Daniel C....
Transcript of Incidence of Infective Endocarditis due to Viridans Group ...€¦ · 11/6/2012 · Daniel C....
Muhammad R. Sohail, James M. Steckelberg, Walter R. Wilson and Larry M. BaddourDaniel C. DeSimone, Imad M. Tleyjeh, Daniel D. Correa de Sa, Nandan S. Anavekar, Brian D. Lahr,
Publication of the 2007 American Heart Association's Endocarditis Prevention GuidelinesIncidence of Infective Endocarditis due to Viridans Group Streptococci Before and After
Print ISSN: 0009-7322. Online ISSN: 1524-4539 Copyright © 2012 American Heart Association, Inc. All rights reserved.
is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231Circulation published online June 11, 2012;Circulation.
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DOI: 10.1161/CIRCULATIONAHA.112.095281
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Incidence of Infective Endocarditis due to Viridans Group
Streptococci Before and After Publication of the 2007 American
Heart Association’s Endocarditis Prevention Guidelines
Running title: DeSimone et al.; Incidence of VGS endocarditis
Daniel C. DeSimone, MD1; Imad M. Tleyjeh, MD, MSc2,6;
Daniel D. Correa de Sa, MD3; Nandan S. Anavekar, MBBCh4; Brian D. Lahr, MS5;
Muhammad R. Sohail, MD6; James M. Steckelberg, MD6; Walter R. Wilson, MD6;
Larry M. Baddour, MD6 for the Mayo Cardiovascular Infections Study Group
1Dept of Internal Medicine, Mayo Clinic, Rochester, MN; 2Division of Infectious Diseases, King Fahd Medical Center, Riyadh, Saudi Arabia; 3 Dept of Medicine at the University of Vermont
College of Medicine & Fletcher Allen Health Care, Burlington, VT; Divisions of 4Cardiovascular Diseases, 5Biomedical Statistics & Informatics, 6Infectious Diseases, Mayo
Clinic College of Medicine, Rochester, MN
Correspondence:
Daniel C. DeSimone, MD
Department of Internal Medicine
Mayo Clinic
200 First Street SW
Rochester, MN 55905
Tel: 507-226-3319
Fax: 507-284-3256
E-mail: [email protected]
Journal Subject Codes: [111] Infective endocarditis, [8] Epidemiology
, ; g, ; , ;
Larry M. Baddour, MD6 for the Mayo Cardiovascular Infections Study y GrGrrouuup pp
Deptpt of Internal Medicine, Mayo Clinic, Rochester, MN; 2Division of Infectious Diseases, KingFaFaahdhdhd MM Medededicicical CCCeenenter, Riyadh, Saudi Arabia; 33 D DDeept of Medicinne e e at tthehehe U University of Vermont
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Abstract:
Background - The American Heart Association (AHA) published updated guidelines for
infective endocarditis (IE) prevention in 2007 that markedly restricted the use of antibiotic
prophylaxis in certain at-risk patients undergoing dental and other invasive procedures. The
incidence of IE due to viridans group streptococci (VGS) in the United States following
publication of the 2007 AHA guidelines has not been reported.
Methods and Results - We performed a population-based review of all definite or possible cases
of VGS-IE using the Rochester Epidemiology Project of Olmsted County, Minnesota. Patient
demographics and microbiologic data were collected for all VGS-IE cases diagnosed from
January 1, 1999 through December 31, 2010. We also examined the Nationwide Inpatient
Sample (NIS) hospital discharge database to determine the number of VGS-IE cases included
between 1999 and 2009. We identified 22 cases with VGS-IE in Olmsted County over the 12-
year study period. Rates of incidence (per 100,000 person-years) during time intervals of 1999-
2002, 2003-2006, and 2007-2010, were 3.19 (95% confidence interval [CI], 1.20-5.17), 2.48
(95% CI, 0.85-4.10), and 0.77 (95% CI, 0.00-1.64), respectively (p-value=0.061 from Poisson
regression). The number of hospital discharges with a VGS-IE diagnosis in the NIS database
during 1999-2002, 2003-2006, and 2007-2009 ranged between 15,318-15,938, 16,214-17,433,
and 14,728-15,479, respectively.
Conclusions - Based on data complete through 2010, there has been no perceivable increase in
incidence of VGS-IE in Olmsted County, MN following publication of the 2007 AHA
Endocarditis prevention guidelines.
Key words: endocarditis, guidelines, infective endocarditis, prevention, dental prophylaxis
p ( ) p g
between 1999 and 2009. We identified 22 cases with VGS-IE in Olmsted Counttyy y ovovverrr t tthehehe 11 122-2-
year study period. Rates of incidence (per 100,000 person-years) during time intervals of 1999-
2002, , 2003-2006,6, and 2007-2010, were 3.19 (95%5 confidence interval [[CIC ], 1.20-5.17), 2.48
995%5%5% C CI, 00.8.8.8555-4.4.1010),), andnd 00.7. 7 (9(95%% CCI, 00.00-1.1 64644), respspecectivelyy ( ((pp-p-vavaluluee=0.06061 1 fromm PPoioisson
eegrrrese sion). TThehe nn uumumbebeb rr r ofofof h h hooospipitatatall l didiscsccharggeees wwiithhh a VVVGSGSS-IIIE E dddiaaagnonosiss ss inin tthhehe NNNISISIS d d daaatababbasasee e
duduuririnngng 1999-9-20202 00202,,, 20200303-2000006,6, a a ndndd 2 2 2000077-7-20200999 r ranannggeged d d bebeetwtwweeeen 11515,3,318--15,5,999388,8, 16,6,,22114--177,4,433333,,
and d 1414 7,7228-15,5,474 9,9, rrese pectc ivvelely.y
Conclusionnss s -- BaBaB ssesedd d ononon ddatatataaa cocompmpm leleletee tt thrhrh ouououghghgh 22 20101010,0,0 theheherrreee hahahasss bebeb enenen n nnoo pepepercrceieiivavvablblble ee ininincrease in
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Introduction
Despite advances in medical, surgical, and critical care interventions, infective endocarditis (IE)
remains a life-threatening illness1. Therefore, implementation of effective prophylaxis measures
is highly desirable. Based on the known risk of bacteremia during invasive procedures, the
American Heart Association (AHA) has published formal recommendations for IE prophylaxis
since 1955. Over the years, however, cumulative evidence has suggested that the risk of
bacteremia during invasive dental procedures is not substantially greater than the risk during
activities of daily life2. Based on availability of these and other more recently published data3,
the AHA made radical changes in their IE prevention guidelines in 2007 that recommended use
of antibiotic prophylaxis for invasive dental procedures to only four groups of patients who
would be at higher risk from complications and mortality if they developed endocarditis4.
Moreover, the 2007 guidelines no longer recommended antibiotics for IE prevention before
invasive gastrointestinal and genitourinary procedures4.
Because invasive dental procedures have been linked to IE due to viridans group of
streptococci (VGS) in the past, there has been a lingering concern among medical and dental
health care providers that the decrease in the number of patients receiving antibiotic prophylaxis
for invasive dental procedures may result in an increase in cases of VGS-IE. However,
prophylaxis restrictions introduced in the updated guidelines on the incidence of IE due to VGS
in this country remains undefined.
We performed a temporal trend analysis of the incidence of IE due to VGS in Olmsted
County, MN, between 1999 through 2010, which included an analysis of incidence both before
and after publication of the 2007 AHA endocarditis prevention guidelines. We also evaluated the
number of hospital discharges due to VGS-IE using the Nationwide Inpatient Sample (NIS)
of antibiotic prophylaxis for invasive dental procedures to only four groups of paaatttienenentsss w wwhohoho
would be at higher risk from complications and mortality if they developed endocarditisf 4.
MoMoorerreovovovererr, , thththee 2020000707 guidelines no longer recommmmmennnded antibioticccs s foor r IEIEIE prevention before
nnvaaasis ve gastrroioiinnnteeestitiinnnal l l ananand d d geggeninitotot uururiinnaaary ppproooceddduurress444..
BBececcauauausese iinvnvvasasivivee e ded ntntntalall pp prororoceceddudurereress s hahaavevev bebebeenen l ininnkekeked d tototo I IIE E dududuee e tooo v viririrididdanana ss s ggrgrououup p ofof
treptococci ( (VGVGVGS)S)S) i iin n n ththhe papapaststs , thththererere e e hahaas s s bebebeenenen a a a lllininingegegerir ngngng cccoooncncncererern n amamamononong g g memem dididicacacal ll ananand d dental
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database between 1999 and 2009.
Methods
Setting
Olmsted County, Minnesota, provides an exceptional opportunity to conduct population-based
studies given its geographic isolation from other urban centers, as well as a unique medical
records-linkage system that encompasses all residents of Olmsted County, regardless of their
healthcare provider. Our group has previously performed two population-based analyses of IE in
Olmsted County within the past decade that included cases between 1970 and 20065,6. During
this time period, there was a total of 150 cases of IE with an incidence of VGS-IE ranging from
1.7 to 3.5 cases per 100,000 person-years5,6.
Data Collection
The Endocarditis Registry of the Division of Infectious Diseases at Mayo Clinic and the
Rochester Epidemiology Project (REP) database were our primary resources for data collection
and case ascertainment. The IE registry at Mayo Clinic is a prospectively maintained database of
all IE cases since 19705. Patient medical records were retrieved through the REP database, which
links and indexes diagnostic and procedure information from all sources of health care in
Olmsted County into a single centralized system5. All Olmsted County residents 18 years or
older with definite or possible IE caused by VGS, as defined by the modified Duke criteria,
between January 1, 1999, and December 31, 2010 were identified using this system6,7. We
obtained demographic, clinical, laboratory, and outcomes data from a detailed review of the
complete medical records.
his time period, there was a total of 150 cases of IE with an incidence of VGS-IIEEE raraangngginining g g frfrfromom f
1.7 to 3.5 cases per 100,000 person-years5,6.
DaDatatata C C C lolollelelectctctiion n
TThee e EnE docarddititisisis RRRegegisi trtrtry y ofofof t tthhehe DDDiivivisssiooon ooff IIInfectctiiouuss DDDisisseaaasesesss aaat MMaayayoo ClClClininnicic a aandndnd ttheheh
RoRoochchchesesesteterr EpEpEpididememmioiololoogyyy PProojejej ctctct (( (REREREP)P)P) dddatatataaabasasase e wewewereee o oururur p p pririimamamaryryry r r resese ououourcrceseses f ffororo d ddatatata a cccolllllecectttioonon
and case ascererrtatataininnmemementntn .. Thhhe e e IEIEI rrregege isisistrt y y y atatat M MMayayayo o o CCClilininin c c isisis aaa p pprororospspspeccctitit vevevelylyly m m maiaintntntaiaiainenened d d database off
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The NIS database has been previously described8. The NIS is a stratified probability
sample developed as part of the Healthcare Cost and Utilization Project (HCUP) funded by the
Agency for Healthcare Research and Quality (AHRQ). The NIS contains data from
approximately eight million hospital admissions each year9. Discharge records were queried
using ICD-9-CM codes to determine the number of cases of VGS-IE that occurred between 1999
and 2009; the data for 2010 is not currently available. The following ICD-9-CM codes were used
in combination to identify VGS-IE cases: acute or sub-acute bacterial endocarditis: 421.0;
streptococci unspecified: 041.00; and other streptococci: 041.09. We excluded the following
ICD-9-CM diagnostic codes from our search: streptococcus group A: 041.01; streptococcus
group B: 041.02; streptococcus group C: 041.03; enterococcus group D: 041.04; streptococcus
group G: 041.05.
We surveyed the local dental society membership regarding aspects of the 2007 AHA IE
prevention guidelines changes. The following questions were included in a questionnaire: 1) Do
you treat patients who live in Olmsted County; 2)Are you aware of the changes in the 2007
AHA/ADA endocarditis prophylaxis guidelines; 3) Did you revise your practice to include the
2007 guidelines; 4) Do you still use the guidelines that were available before 2007? If so, in
whom; and 5) Do you think it is important to monitor the incidence of endocarditis due to
viridans group streptococci following publication of the 2007 guidelines.
The antimicrobial susceptibilities of all cases of VGS-IE between 1999 and 2010 in
Olmsted County database were recorded from in-vitro susceptibility testing. Minimal inhibitory
concentrations (MICs) were determined by standard broth microdilution techniques and
interpreted in accordance with Clinical and Laboratory Standards Institute (CLSI)
breakpoints10,11.
group B: 041.02; streptococcus group C: 041.03; enterococcus group D: 041.04; ; ststrerer pptptococococococcucuc s s
group G: 041.05.
WWWee e susuurvveyeyeyedede the local dental society meemmbmbeership regardiingngn aspsppeecects of the 2007 AHA IE
prevvvene tion guiuidededeliineness chhhananngegegesss. T Thhehe ffoolllooowinngng queeessttionnns s weweereee iinnccluuudeded dd innn a a quququesestitiionononnanairi ee:e: 1 1) )) DDDo
yoyou uu trtrtreaeae tt papapatititienenttss wwwhohoo liivivee innn O O Olmlmlmstststeded CC Cououounnnty;y;y; 2 2)A)A)Arre yyyououou a a awawawareree o offf ththt eee cchhananngegeges s ininn t tthhehe 22000007 7
AHA/ADA enenndodod cacacardrdr itititisiss p prororophphp ylylylaxaxa isisis g guiuiu dededelililinenenes;s;s; 3 3) ) ) DiDD d d d yoyoyou u u rereevivivises yoyoyoururur p p prararactcticicice e e tototo i i incncn lude the
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Site of infection acquisition of was defined as described by Friedman et al12. Patients
were considered to have health care-associated infection if one of the following conditions were
met before the development of signs or symptoms of IE: received infusion therapy at home or
self-administered intravenous medications in the last 30 days; attended a hospital or
hemodialysis center or received intravenous chemotherapy in the last 30 days; was hospitalized
in an acute care hospital for 2 or more days in the preceding 90 days; or resided in a nursing
home or a long-term care facility6,11. Community acquisition of IE was defined by onset of signs
and symptoms of IE in patients who did not fit the above criteria for a health-care associated
infection12. Nosocomial acquisition of IE was defined by onset of signs and symptoms of IE in
patients who had been hospitalized for 48 hours or longer 6.
Statistical Analysis
Incident cases were residents of Olmsted County, Minnesota that first tested positive for VGS-IE
in the 1999-2010 time frame. We calculated incidence rates as the number of VGS-IE cases per
100,000 person-years, assuming that the entire adult population was at risk. The denominators of
age- and sex-specific person-years were derived from census figures and then directly adjusted to
the Caucasian population in the United States in year 2000. Ninety-five percent confidence
intervals were estimated assuming that the incidence cases followed a Poisson distribution.
Finally, a multivariable Poisson regression model was fit to the data to test for a temporal trend
in the incidence of VGS-IE over the study time frame (time was grouped into three 4-year
intervals and fit as a categorical variable), adjusted for age and sex. All analyses were carried out
using the SAS statistical software package (Version 9.2, SAS Institute Inc., Cary, NC). A p-value
< .05 was considered statistically significant.
patients who had been hospitalized for 48 hours or longer 6.
Statistical Analysis
nnciciidededentntnt c ccasasasess wwererere e residents of Olmsted County,y,y MMMinnesota thatt f firstt ttteeesststed positive for VGS-IE
nn thhehe 1999-200101010 ttimimee e frfrramammee.e. W WWe cacacalclcululaateddd innncidddennnce e raraatetesss aasas tthhehe nnumummbbeer r ofofof VVGSGSGS-I-I-IEE caaasseses s ppeer
10000,0,0,00000000 pepepersrsrsonon-y-y-yeeaearsrs,,, asasssusummimingngng tt thahahatt ththhe e enenentttireee a a ddudulltlt p ppopopopulululaaatioioonn wawaass s atatt riissk.k T T heheh d ddenenenomomminnnatatooorss s of
age- and sexx-s-sspepepeciciififific c pepepersononon-y-yyeaeaearsrsr w wwerrree e dedederiririveveved d d frfrfromomom ccenenensususus ss fififigugugureees ss ananand d d thththenen d ddiririrececectltlly yy adjusted ttoom
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Results
We identified 22 cases of VGS-IE in Olmsted County adult population between the years 1999
and 2010. The age- and sex-adjusted incidence rates of VGS-IE in Olmsted County, MN, for
1999-2002, 2003-2006, 2007-2010, was 3.19 (95% CI, 1.20-5.17), 2.48 (95% CI, 0.85-4.10), and
0.77 (95% CI, 0.00-1.64) per 100,000 person-years, respectively (Figure 1).
Only three of the 22 (13.6%) VGS-IE cases were identified between 2007 and 2010. Of
these, two patients had not undergone any dental treatments within six months of admission. The
remaining patient had a dental procedure two weeks prior to symptom onset, and had taken
clindamycin 600 mg by mouth 30 minutes prior to the dental procedure.
Penicillin susceptibility was screened among the strains of all 22 VGS-IE cases; 21
isolated (95.5%) were susceptible to penicillin, one isolate (4.5%) was intermediately susceptible
and none were resistant. Twenty-one of the 22 isolates were also screened for macrolide
susceptibility, 15 (71.4%) were susceptible while 6 (28.6%) were resistant. Clindamycin
susceptibility testing was not performed.
IE cases were classified based on site of infection acquisition. Using the definitions
described above, 91% (20/22) were classified as community-acquired, 9% (2/22) were health
care-associated; and there were no cases that were nosocomially acquired. The two strains of
VGS that were classified as healthcare-associated were both sensitive to penicillin.
Between 1999 and 2009, VGS-IE discharge data were accessible with the NIS database.
The total number of VGS-IE cases from the NIS database, based on the ICD-9 codes listed in
hospital discharges during 1999-2002, 2003-2006, and 2007-2009 ranged between 15,318-
15,938, 16,214-17,433, and 14,728-15,479, respectively (Figure 2).
Penicillin susceptibility was screened among the strains of all 22 VGS-IEEE casaa eess; ;; 212121
solated (95.5%) were susceptible to penicillin, one isolate (4.5%) was intermediately susceptible
annd d d nonononnene ww wererre rereesisisists ant. Twenty-one of the 22 isssoolo aaates were also ssscreeeenenened d for macrolide
uuscccepe tibility, 151515 (((7111.4.4. %)%)%) w werereree susuuscsccepepptiibble whwhwhile 66 (288.8.6%6%6%) ) wwewerrre rresesisisistatantnt. ClClClinindadadammymyccic n n n
uuscscscepepeptitit bibililiitytyty t tesessttinngng w wwaasas nnotott p p perererfofoforrmrmeeded.
IE caasesees s s wewewererer c cclalal ssssififi ieieied d bababaseseed d ononon s ssititte e e ofofof iiinfnfnfececectit ononon a aacqcqcquiuiuisisisitit ononon. . UsUsUsinining gg ththhe e e dededefififininin tions
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Discussion
To our knowledge, this is the first population-based study in the United States to examine the
incidence of VGS-IE in adults following the publication of the updated 2007 AHA IE prevention
guidelines. Our investigation demonstrated no perceivable increase in incidence following
publication of these guidelines.
Because there are no previously published prospective, randomized, placebo-controlled
trials to evaluate either the risk of VGS-IE due to dental procedures or the efficacy of antibiotic
prophylaxis in this setting, and the likelihood of such trials being conducted is very low,
population-based investigations are critical in evaluating IE prevention practices.
Three other investigations support our findings that the incidence of VGS-IE has not
increased following publication of the 2007 AHA endocarditis prevention guidelines. This
includes our evaluation of the NIS database from 1999 to 2009 that contained the total number of
hospital discharges due to VGS-IE. The NIS is the largest all-payer inpatient care database in the
United States that includes approximately a 20% stratified sample of U.S. community hospitals9.
Discharge data in 1999 included 24 states, 984 hospitals, and 7,198,929 discharges, while in
2009, there are 44 states, 1,050 hospitals and 7,810,762 discharges. Over the 11-year period, the
number of states and total discharges increased, while the number of hospitals slightly increased.
The number of hospital discharges due to VGS-IE remained stable between 1999 and 2009,
despite increases in the number of states, hospitals, and total discharges that were surveyed.
The second investigation is a hospital-based survey13 that, in response to the publication
of the updated 2007 AHA prophylaxis guidelines, examined the number of patients hospitalized
at a university teaching hospital with a discharge diagnosis of acute or subacute bacterial
endocarditis between May 2001 to April 2007 and May 2007 to January 2008. This preliminary
Three other investigations support our findings that the incidence of VGSGSS-I-IE EE hahahass s nononot t t
ncreased following publication of the 2007 AHA endocarditis prevention guidelines. This
nnclclludududeeses o ooururu eeevaalululuaatation of the NIS database frommm 1 9999 to 2009 thhataa cononntatatained the total number o
hhohosppspital dischharargggess dududue tototo V V VGSGSGS-I-IE.E.E TThhehe NISSS iis thhee llargggeesest t aala ll--papayeyeer ininppapattienenntt cacareree d d datata ababa asasase e inini tthe
UnUnnititi ededed S Statatetetesss ththaaat iincnclluluddedess aappppp rororoxixiximmamattetelylyly a a a 20%0%0% s strtrratatififi ieieedd d sasampmpm lele oo of f f UUU.SSS. ccomomommumuunininityty hhoosospipiitatallsls9.
Discharge daatatata i iin n 19191999999 iinccclululudedd d d d 24242 s sstaaatetetes,s,s, 9898984 4 4 hohoospspspititi alals,s,s, a a andndnd 777,1,1,198988,9,9,9292929 d ddisisschchc ararargegeges,s,s, w wwhile in
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survey revealed that the number of patients with IE over the two time periods had not changed
substantially.
The third and most supportive study is from the National Institute for Health and Clinical
Excellence (NICE) in the United Kingdom that also published guidelines that addressed
antibiotic prophylaxis for IE in 200814. These guidelines recommended that antibiotic
prophylaxis before dental procedures, solely to prevent IE, should not be administered to any
group of patients, regardless of their anticipated risk of IE complications. This radical change in
recommendations sparked immediate controversy and anecdotal claims of a possible increase in
the number of cases of VGS-IE15,16 among clinicians in England.
Thornhill et al17 defined the impact of the NICE guidelines in the first two years after
publication of these guidelines by quantifying the change in prescribing patterns of antibiotic
prophylaxis before invasive dental procedures for patients at risk of IE, and any concurrent
change in the incidence of IE in the United Kingdom. Using the national database, they were
able to survey the entire country regarding the practice of antibiotic prophylaxis for dental
procedures. In their investigation, they identified patients who received a unique 3 gram dose of
amoxicillin prior to invasive dental procedures and compared that to denominator data of IE
cases. Their analysis indicated a 78.6% reduction in prescribing of antibiotic prophylaxis after
the introduction of the NICE guidelines. Yet, they did not detect a significant increase in the
number of IE cases above the long-term baseline trend during their study period. There was no
significant increase in the rate of IE-related in-hospital mortality or increase in the number of IE
cases due to streptococci of oral origin. The estimated annual percentage change in the number
of oral streptococcal IE cases from January 2000 to March 2008 was 8.41% (95% CI, 6.66%-
10.19%); the estimated change after the new guidelines was 10.38% (95% CI, 2.93%-18.36%);
Thornhill et al17 defined the impact of the NICE guidelines in the first twowoo yyyeaearsrss a a aftftftererer
publication of these guidelines by quantifying the change in prescribing patterns of antibiotic
prropopophyhyhyllalaxixixis s s bebb fofoorerere iinvasive dental procedures fofoor rr pppatients at riskk o oof IEEE, , aanand any concurrent
hchhannange in the ininccic dddencncce ofofof I I IE EE iinin thhehe U Uninitted KiKiKingddodomm. UUUsisinngng tthehe nnatatioionnnall dadaatatatabbabasesee, , thththeyeyy wwwereree
abbblelele t ttoo o susurvrvveyeey tthhee eeentntiirire e cocounnntrtryyy rerereggagardrddininngg g tththe ee prprpraacactitit ceee ooofff aanantititibibib oototicicic p p prroophphhylyllaxaxaxisisi f ffororor d deeenttatal l
procedures. InInn t t theheheiririr i invnvnvesee tiiigagagatitt ononon, , ththheyey i iidededentntntififfieieied d d papapatitit enenntststs wwwhohoho r r recece eieieiveveved d d a a a unununiqiqqueueue 3 3 3 g ggrarar m dose of f
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(P=0.66). Twelve-months prior to the NICE guidelines, dentists accounted for 91.9% of
prescriptions for antibiotic prophylaxis, while 14-25 months after the introduction of the
guidelines, the number of prescriptions written by dentists significantly decreased by 79.9%.
These data support the recommendations published in the NICE guideline17.
To evaluate the antibiotic prescribing pattern for IE prophylaxis in Olmsted County, we
performed an ancillary survey of the local dental society (90 members) and had a 41.1%
response rate to a brief questionnaire. All respondents indicated that they were aware of the 2007
AHA IE prevention guidelines and had modified their respective practices to include the new
recommendations for antibiotic prophylaxis. The results of our survey regarding awareness and
implementation of the 2007 AHA guidelines among local dental practitioners are consistent with
the trends noted by the American Dental Association (ADA; Peter Lockhart, personal
communication). The ADA collected data from 901 respondents, which included its members
and non-members in a questionnaire regarding the 2007 AHA guidelines and found that self-
reported awareness of the updated guidelines was almost universal (97.9%) and 77% of dental
practitioners were either satisfied or very satisfied with the guidelines. Eighty percent of
respondents reported a decrease in the number of patients who received antibiotic prophylaxis.
The incidence of VGS-IE in Olmsted County has been declining since its peak in 1985-
19895,6. Factors responsible for this observation have been undefined, to date. It is tempting to
speculate that the decline in VGS-IE cases could be related to the overall decline in rheumatic
carditis as a unique substrate for the development of IE due to VGS. Studies18-20 from areas
where rheumatic fever continues to be endemic and a prominent predisposing condition for the
development of IE describe VGS as the predominant pathogens.
Our study has limitations. The adult population of Olmsted County is <150,000 people,
mplementation of the 2007 AHA guidelines among local dental practitioners arre ee cooonsssisisistetetentntnt wwith
he trends noted by the American Dental Association (ADA; Peter Lockhart, personal
coommmmmmuununicicicatatatioioi n)).. TThThe ADA collected data from 9909011 respondents,, w wwhiichchch i incn luded its members
anndd d non n-membmbererrs inn a aa q qq eueuesststioioionnnnnaiaiaireree r regegardiiinggg theee 2200007 7 AHAHHAA A guguuiddelelinininesss aandndnd ffououndndnd t t hahahat sseselflflf-
eepopoportrtrtedede a awawawarereneneessss ooff f thhhe e upupdadadateteteddd gguguididdelelelininineees wwwaas ss aallmmomoststst u u unnniveveversrssalall ( ( (97977.99%%) ) ananand dd 777777%% % ooof dddenenntatall l
practitioners s wewewereree e e eititi heheh r rr saaatitit sfsfs iededed o or r r veveeryryry s s satatatisisisfififiededd w wwitith h thththee e guguguidididelee innneseses.. . EiEiEighghghtyty p pperererceceentntn of
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DOI: 10.1161/CIRCULATIONAHA.112.095281
11
which results in a small number of annual cases of VGS-IE. In addition, the time interval of our
investigation following publication of the guidelines was relatively short. A delay between
publication of the guidelines and implementation into clinical practice by healthcare
professionals is characteristically seen with most guidelines; thus, it may take several years
before the impact of these guidelines is evident. Nevertheless, we did not detect an increase in
incidence of VGS IE during the 12-year study period. In addition, the racial homogeneity in
Olmsted County (predominately Caucasian) may limit applicability of the study findings to more
diverse populations. Furthermore, there are limited data on compliance with the guidelines
available and the risk profile of patients who receive prophylaxis is unknown (high-risk vs. low-
risk for complications).
The NIS contains discharge-level records, not patient-level records9, therefore individual
patients who are hospitalized multiple times in one year may be present in the NIS multiple
times. In addition, diagnosis codes may not be accurate in defining disease syndromes.
Finally, self-reported data in response to a survey may not be a true reflection of actual practice
behavior. Responders may be more likely that the non-responders to be aware of and follow the
2007 guidelines. For a more accurate estimation of adherence to new practice guidelines, patient
records would need to be reviewed, and this was not performed in our investigation.
Conclusions
Despite marked changes in IE prevention guidelines that were published by the AHA in 2007
that restricted antibiotic prophylaxis to four patient groups with a high-risk of complications
from IE, the findings of our population-based investigation from Olmsted County, Minnesota
suggest that the incidence of VGS IE following publication of these guidelines did not increase.
isk for complications).
The NIS contains discharge-level records, not patient-level records9, therefore individual
paatitiienenentststs w wwhohoho aaree hh hoosospitalized multiple times in ononone year may be prprpresenenntt t iinin the NIS multiple
iiimeemes.s In addititiononn, didiiaaggnnonosisisis s cococodedes ss mmamayy nnot bebee accccuuuratte e e inin d ddeeffininiininggg didiisseeaase e sysysyndndroroommemess..
FiFinananalllllly,y,y, sselellf-f-f-rerepopoorttteded ddaatata a inn rr esesspopoponsnnse e tototo a a a s s sururrvevev yyy mmmayayy n nnototot b b be ee a aa ttrtrueueue r r refeffleectctioioon n ofofo a aactctctuauaall pprpracacctticcce yy
behavior. Reespspponono dededersrsr m mmayayy b b be e e momomorerer l llikikelele y y y ththhatatat t tthhe ee nononon-n-rererespsppononondededersrsr ttto oo bebebe a a awawawareree o o of f f ananand d d follow the
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DOI: 10.1161/CIRCULATIONAHA.112.095281
12
Continued monitoring of the incidence of VGS-IE over an extended period of time is mandatory,
however, in both local and other populations to substantiate this preliminary finding.
Acknowledgments: Author contributions: Dr. DeSimone had full access to all of the data in the
study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Design and conduct of the study: DeSimone, Tleyjeh, Correa de Sa, Baddour. Acquisition of
data: DeSimone, Steckelberg, Anavekar, Tleyjeh, Correa de Sa, Baddour. Analysis and
interpretation of data: DeSimone, Sohail, Tleyjeh, Correa de Sa, Lahr, Wilson, Baddour. Critical
revisions of the manuscript for important intellectual content: DeSimone, Sohail, Tleyjeh, Correa
de Sa, Lahr, Steckelberg, Anavekar, Wilson, Baddour. Drafting of the manuscript: DeSimone,
Sohail, Tleyjeh, Correa de Sa, Baddour. Statistical analysis: DeSimone, Lahr, Baddour. Obtained
funding: DeSimone, Baddour. Administrative, technical, or material support: Wilson, Baddour.
Study supervision: DeSimone, Steckelberg, Wilson, Baddour. Institutional review board: Mayo
Clinic IRB approved; study ID: 10-007212
Funding Sources: This study was supported by research grants from the Baddour Family Fund,
Mayo Foundation for Medical Education and Research. Role of the Sponsor: The funding
organizations had no role in the design and conduct of the study; the collection, management,
analysis, and interpretation of the data; or the preparation, review, or approval of the manuscript.
Sohail: TyRx Inc. (moderate, $ <10,000). Baddour: Royalty payments-UpToDate, Inc.; Editor-
in-Chief payments-Massachusetts Medical Society (Journal Watch Infectious Diseases); Co-
editorship payments-American College of Physicians (PIER).
Conflict of Interest Disclosures: None
References:
1. Baddour LM, Wilson WR, Bayer AS, Fowler VG, Bolger AF, Levison ME, Ferrieri P, Gerber MA, Tani LY, Gewitz MH, Tong DC, Steckelberg JM, Baltimore RS, Shulman ST, Burns JC, Falace DA, Newburger JW, Pallasch TJ, Takahashi M, Taubert KA. Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology,
funding: DeSimone, Baddour. Administrative, technical, or material support: WiWilslslsononon, BaBaBaddddddououourr.r
Study supervision: DeSimone, Steckelberg, Wilson, Baddour. Institutional reviewew bb booaoardrdrd::: MaMaMayooyo
Clinic IRB approved; study ID: 10-007212
FFuFunndnding Sooururcececes:s: ThThThiisis ss stututudydyy w w wasasa ss supupuppopoortrttededed b b by y rresssearrrchchch g g grranana tstss f roroomm m thththeee BaBaaddddddououourrr FaFaFammimilylyly F F Fununund,
MMMayyoyo Founddata ioonn for MMMediicccall l Edducccatatiioionnn annd Resseaararchchh. RoRoRolee of f thhe Sppponnnsooor:: TT he ffuunndddinng
ororgaanininizazazatititioonons s hahahaddd nonono rr rolololee e ini tthehehe d d deesesigign n ananand dd cococondndnducucucttt ofofof tt thehehe s sstututudyddy; ; thththee e cococollllllecece titiiononon, , mammananaagegegememementntnt,
analysis, and d ininintetet rprprprerer tatatatitit onnn o oof ff thhhe e e dadaatat ; ; ; ororor t thehehe p p prererepapaparararatit ononon,, rerereviviiewewew, ororor a aapppppprororovavav l l l ofofof ttthehehe m m anuscriptt.
by guest on June 11, 2012http://circ.ahajournals.org/Downloaded from
DOI: 10.1161/CIRCULATIONAHA.112.095281
13
Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America. Circulation. 2005;111:e394-434.
2. 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.
3. 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.
4. Wilson W, Taubert KA, Gewitz M, Lockhart PB, Baddour LM, Levison M, Bolger A, Cabell CH, Takahashi M, Baltimore RS, Newburger JW, Strom BL, Tani LY, Gerber M, Bonow RO, Pallasch T, Shulman ST, Rowley AH, Burns JC, Ferrieri P, Gardner T, Goff D, Durack DT. Prevention of infective endocarditis: guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation. 2007;116:1736-1754.
5. 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. de Sa DD, Tleyjeh IM, Anavekar NS, Schultz JC, Thomas JM, Lahr BD, Bachuwar A, Pazdernik M, Steckelberg JM, Wilson WR, Baddour LM. Epidemiological trends of infective endocarditis: a population-based study in Olmsted County, Minnesota. Mayo Clin Proc. 2010;85:422-426.
7. Li JS, Sexton DJ, Mick N, Nettles R, Fowler VG, Ryan T, Bashore T, Corey GR. Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis. 2000;30:633-638.
8. Kopp BT, Wang W, Chisolm DJ, Kelleher KJ, McCoy KS. Inpatient healthcare trends among adult cystic fibrosis patients in the U.S. Pediatr Pulmonol. 2012;47:245-51.
9. HCUP Nationwide Inpatient Sample (NIS). Healthcare Cost and Utilization Project (HCUP). 2007-2009. Agency for Healthcare Research and Quality, Rockville, MD. www.hcup-us.ahrq.gov/nisoverview.jsp. Access date: September 1, 2010.
10. Prabhu RM, Piper KE, Baddour LM, Steckelberg JM, Wilson WR, Patel R. Antimicrobial susceptibility patterns among viridans group streptococcal isolates from infective endocarditis patients from 1971 to 1986 and 1994 to 2002. Antimicrob Agents Chemother. 2004;48:4463-4465.
and Outcomes Research Interdisciplinary Working Group. Circulation. 2007;116:1:17373736-6-17175454..
5. Tleyjeh IM, Steckelberg JM, Murad HS, Anavekar NS, Ghomrawi HM, Mirzoyoyevevev ZZ Z, Moustafa SE, Hoskin TL, Mandrekar JN, Wilson WR, Baddour LM. Temporal trends in nfective endocarditis: a population-based study in Olmsted County, Minnesota. JAMA.
200050505;2;2;2939393:3:3:30202022--303030228.
66.. ddde e Sa DD, TTleleleyjjjehhh II M,M,M, A A Anananavevekakakarr r NNSS,, Schhuhultz JCJCJC, TThThoomomasas JJMMM, LLahahhrrr BBDBD,, BaBaB chchhuwuwuwarar A A A,, PPaPazdddernik M,M,, S teeecckkelbbeberrg JJM,M,M, W Wilsosoonn WWWR, BBaadddououurr LLLM.M.M. E E Epppideemmiiologggicccal trreendn s ofoff i innfnfeeectivveve renndodod cacacardrdititisisis:: : aa ppopopupupulalaattioonon-b-baasasededed ss stttududu y y y innn O O Olmlmlmststs ededd CCCououuntntnty,y,y, M M Minini nnenesososotata.. MMaMayoyoyo CCClilinn n PPrPrococ. 20100;8;855:42422-2 42426.
77 LLii JSJS SeSextxtonon DDJJ MMicickk NN NNetettltleses RR FoFowlwlerer VVGG RRyayann TT BBasashohorere TT CoCorereyy GRGR PrPropopososededrr
by guest on June 11, 2012http://circ.ahajournals.org/Downloaded from
DOI: 10.1161/CIRCULATIONAHA.112.095281
14
11. Knoll B, Tleyjeh IM, Steckelberg JM, Wilson WR, Baddour LM. Infective endocarditis due to penicillin-resistant viridans group streptococci. Clin Infect Dis. 2007;44:1585-1592.
12. Friedman ND, Kaye KS, Stout JE, McGarry SA, Trivette SL, Briggs JP, Lamm W, Clark C, MacFarquhar J, Walton AL, Barth LR, Sexton DJ. Health care-associated bloodstream infections in adults: a reason to change the accepted definition of community-acquired infections. AnnIntern Med. 2002;137:791-797.
13. Rogers AM, Schiller NB. Impact of the first nine months of revised infective endocarditis prophylaxis guidelines at a university hospital: so far so good. J Am Soc Echocardiog.2008;21:775.
14. Richey R, Wray D, Stokes T. Prophylaxis against infective endocarditis: summary of NICE guidance. BMJ. 2008;336:770-771.
15. Connaughton M. Commentary: Controversies in NICE guidance on infective endocarditis. BMJ. 2008;336:771.
16. Stern SR. Infective endocarditis. Time to monitor incidence after NICE guidance. BMJ.2011;342:d121.
17. Thornhill MH, Dayer MJ, Forde JM, Corey GR, Hock G, 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.
18. Kanafani ZA, Mahfouz TH, Kanj SS. Infective endocarditis at a tertiary care centre in Lebanon: predominance of streptococcal infection. J Infect. 2002;45: 152-9.
19. Trabelsi I, Rekik S, Znazen A, Maaloul I., Abid D., Maalej A., Kharrat I., Ben Jemaa M., Hammemi A., Kammoun S. Native valve infective endocarditis in a tertiary care center in a developing country (Tunisia). Am J Cardiol. 2008;102: 1247-1251.
20. Koegelenberg CFN, Doubell AF, Orth H, Reuter H. Infective endocarditis in the Western Cape Province of South Africa: a three-year prospective study. Q J Med. 2003;96:217-25.
16. Stern SR. Infective endocarditis. Time to monitor incidence after NICE guidadaanccce. BMBMBMJ.J.J2011;342:d121.
17. Thornhill MH, , Dayer MJ, Forde JM, Corey GRG , Hock G, Lockhart PB. Impact of the NICE guguididdelelelinininee rererecocoommmmmeenending cessation of antibiotic prprp oophylaxis for prprprevenenntititiooon of infectiveenenndodoocardittisis: : : bebefofoorerer a andndnd a aaftftfterer s stututudydydy. . BMBMJ.J. 20201111;3;34222:d23233929292...
18188. KKaK nafanini Z ZAAA, MMMahhhfofoouzz TTHH,H, KKanannjj SSSSS. Innfeectivvve enendododoccacardrr iiitis att a terrrtiiaaryyy cccarare ccecenntntreree iinn LeLebababanononon:n: p p prereredodomimiminanan ncnncee e ofof sstrtrt epepptototococcocccccalall i i infnfnfeccctitit ononn. JJ IInInfefefectctct.. 22200000 2;2;2 454545:: 111522-2-9.9.9
19. Trabelsi II, , ReReR kikik kk k S,S,S Z Znananazezezen n A,A,A M MMaaaalololoululul I II.,., AbAbAbididd DDD.,, M MMaaaaaalelelej j j A.AA , , KhKhKharararrararatt t I.I.,, BeBeBen n n JeJeJemam a M.,HaHammmmememii AA KaKammmmouounn SS NNatativivee vavalvlvee ininfefectctivivee eendndococarardidititiss inin aa tterertitiararyy cacarere ccenenteterr inin aa
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Figure Legends:
Figure 1. Temporal trends in age- and sex-adjusted incidence rate of infective endocarditis (IE)
caused by viridans group streptococci (VGS) from 1999 to 2010 in Olmsted County, Minnesota.
Figure 2. Total number of hospital discharges with ICD-9-CM discharge diagnosis of 421.0,
041.00, and 041.09 from 1999 to 2009 from the Nationwide Inpatient Sample.
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Time EraVGS-IE
casesIncidence Rate (per 100,000 person-years)
95% Confidence Interval
F M T F M T
1999-2002 1 9 10
0.64(0.00 – 1.89)
6.63(2.18 – 11.09)
3.19(1.20 – 5.17)
2003-2006 5 4 9 2.43(0.28 – 4.58)
2.26(0.03 – 4.49)
2.48(0.85 – 4.10)
2007-2010 0 3 3 0.0(0.0 – 0.0)
1.59(0.00 – 3.42)
0.77(0.00 – 1.64)
TTimee EEraa
nnIncicici edede ccnce e RaRaR tetete (( (pepp rrr 10101 0,00 0000000 0 0 pepepe srsonon y-y-y aaearsrs)))9595% % CoCoC nfnfididene cece I Intnterervall
FFF
VGGVGS-S-S-IEIEIEcacasesess
MM TT FFF MM TTT
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0
2000
4000
6000
8000
10000
12000
14000
16000
18000
20000
1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009Years
Tota
l num
ber o
f dis
char
ges
000
000000
0000000
00000000
000
000
000
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