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.

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DOI: 10.1161/CIRCULATIONAHA.112.095281

1

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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2

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




3

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




4

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




5

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




6

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




7

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




8

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




9

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




10

(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




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




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

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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.




13

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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




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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.

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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.

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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




15

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.



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



0

2000

4000

6000

8000

10000

12000

14000

16000

18000

20000

1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009Years

Tota

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f dis

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ges

000

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incidence of infective endocarditis due to viridans group ...€¦ · 11/6/2012 · daniel c....

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