Skip to main content
Browse Subject Areas

Click through the PLOS taxonomy to find articles in your field.

For more information about PLOS Subject Areas, click here.

  • Loading metrics

Infective Endocarditis Epidemiology Over Five Decades: A Systematic Review

  • Leandro Slipczuk,

    Affiliations Department of Medicine, Einstein Medical Center, Philadelphia, Pennsylvania, United States of America, Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America

  • J. Nicolas Codolosa,

    Affiliation Einstein Institute for Heart and Vascular Health, Einstein Medical Center, Philadelphia, Pennsylvania, United States of America

  • Carlos D. Davila,

    Affiliation Department of Medicine, Einstein Medical Center, Philadelphia, Pennsylvania, United States of America

  • Abel Romero-Corral,

    Affiliation Einstein Institute for Heart and Vascular Health, Einstein Medical Center, Philadelphia, Pennsylvania, United States of America

  • Jeong Yun,

    Affiliations Department of Medicine, Einstein Medical Center, Philadelphia, Pennsylvania, United States of America, Pulmonary and Critical Care Medicine Division, Brigham and Women’s Hospital, Boston, Massachusetts, United States of America

  • Gregg S. Pressman,

    Affiliation Einstein Institute for Heart and Vascular Health, Einstein Medical Center, Philadelphia, Pennsylvania, United States of America

  • Vincent M. Figueredo

    Affiliations Einstein Institute for Heart and Vascular Health, Einstein Medical Center, Philadelphia, Pennsylvania, United States of America, Jefferson Medical College, Philadelphia, Pennsylvania, United States of America


15 Oct 2014: The PLOS ONE Staff (2014) Correction: Infective Endocarditis Epidemiology Over Five Decades: A Systematic Review. PLOS ONE 9(10): e111564. View correction



To Assess changes in infective endocarditis (IE) epidemiology over the last 5 decades.

Methods and Results

We searched the published literature using PubMed, MEDLINE, and EMBASE from inception until December 2011.

Data From

Einstein Medical Center, Philadelphia, PA were also included. Criteria for inclusion in this systematic review included studies with reported IE microbiology, IE definition, description of population studied, and time frame. Two authors independently extracted data and assessed manuscript quality. One hundred sixty studies (27,083 patients) met inclusion criteria. Among hospital-based studies (n=142; 23,606 patients) staphylococcal IE percentage increased over time, with coagulase-negative staphylococcus (CNS) increasing over each of the last 5 decades (p<0.001) and Staphylococcus aureus (SA) in the last decade (21% to 30%; p<0.05). Streptococcus viridans (SV) and culture negative (CN) IE frequency decreased over time (p<0.001), while enterococcal IE increased in the last decade (p<0.01). Patient age and male predominance increased over time as well. In subgroup analysis, SA frequency increased in North America, but not the rest of the world. This was due, in part, to an increase in intravenous drug abuse IE in North America (p<0.001). Among population-based studies (n=18; 3,477 patients) no significant changes were found.


Important changes occurred in IE epidemiology over the last half-century, especially in the last decade. Staphylococcal and enterococcal IE percentage increased while SV and CN IE decreased. Moreover, mean age at diagnosis increased together with male:female ratio. These changes should be considered at the time of decision-making in treatment of and prophylaxis for IE.


Infective endocarditis (IE) extols a high cost for society worldwide, with a US incidence of 10,000 to 15,000 cases each year[1]. IE is associated with prolonged hospitalization, can require surgery[2], and impairs quality of life[3]. IE was initially described in 1885 by Osler[4] as a disease of patients with pre-existing valvular abnormalities. Since then, notable improvements in IE diagnosis and treatment have been made. However, in-hospital mortality is still close to 20 percent[5,6].

Risk factors for IE have changed over time. There have been widespread changes in health-care delivery in the last five decades, which have impacted the clinical spectrum of IE. These include the use of intracardiac devices[7], prosthetic valves[8], hemodialysis[9], and an increase in the elderly population[10]. Furthermore, changes in antibiotics have led to alterations in patterns of infection and bacterial resistance in both the US[11,12] and Europe[13].

In recent decades, several studies have noted an increase in the proportion of IE caused by staphylococcal species[14,15]. However, others have not[16]. A systematic review of population-based studies including 15 studies and 2,371 cases found no significant changes in the causative organism over time[17]. However, significant limitations were present in this study, including a low power to detect changes; nor did it cover the last decade. Moreover, to the best of our knowledge, there are no systematic reviews of hospital based studies.

Proper understanding of IE epidemiology is paramount, as different organisms produce varied complications and may require different treatment and prophylaxis[18]. The objective of this research was to assess whether there have been changes in IE epidemiology globally over the last half century. Towards this end, we performed a systematic review of both population and hospital-based studies.


Data Sources and Searches

We searched, with no language restrictions, PubMed, OVID/MEDLINE and EMBASE electronic databases from their inception to December 2011, for studies reporting infective endocarditis microbiology. We used the term ‘infective endocarditis’ for the Mesh keyword. Date last search performed was December 1st, 2011. We supplemented the search with references from articles reviewed and correspondence with other researchers, including experts in the field. When a reference was deemed potentially suitable for inclusion, a full-text copy was obtained and reviewed according to predefined criteria (listed below). We followed the PRISMA guidelines for systematic reviews.

Study Selection and Data Collection

Prospective and nonprospective studies reporting the frequency distribution of infective endocarditis in the last five decades were included in this systematic review. Two investigators had the protocol for study selection (LS and CD) and independently assessed the studies for eligibility. Inclusion criteria were: (1) a clear definition of the population studied; (2) a clear definition of the time period; (3) a clear definition of infective endocarditis; and (4) a clear description of the frequency distribution of the microbiology encountered. In order to avoid bias, we excluded studies limited to specific populations (e.g. HIV or intravenous drug users). When there was difference of opinion, a third investigator (NC) resolved the disagreement. The authors are fluent in English, Spanish, Portuguese, and Italian; papers in other languages were translated by collaborating physicians who were native speakers. When two studies reported data from the same cohort and time frame, only the most complete one was included. If a study reported data for various time frames, data were analyzed separately for each decade. Kappa (k) for inclusion was calculated from a sample of 10 randomly selected papers. Results were compared and inconsistencies were resolved by consensus. Dr. Andrew Wang from Duke University was consulted for reviewing the list of included studies for completeness.

For each study included, the following information was extracted: first author’s last name, journal, year of publication, IE definition used, certainty (possible IE vs. definite IE), countries, time-frame, multi-center vs. single center, sample size, age, gender, mortality, intravenous drug abuse (IVDA), intracardiac device or prosthetic valve, Staphylococcus aureus (SA), coagulase-negative staphylococcus (CNS), enterococci, Streptococcus viridans (SV) and culture negative (CN) IE.

We also included patients from Einstein Medical Center (EMC), a tertiary 440-bed city hospital in Philadelphia, PA, US; for the years 2000 - 2010. Data were retrospectively extracted per ICD code and then included only if patients met ‘definite’ or ‘possible’ modified Duke criteria[19]. Clinical characteristics were extracted for each patient as mentioned above. This data was added as one more study to the last decade. Sensitivity analyses showed that subtracting this data from the rest did not modify results significance.

Quality assessment

Two reviewers (LS and CD) independently assessed the quality of the manuscripts using the approaches recommended by Khan and colleagues[20] and Stroup and colleagues[21] for cohort studies. The main criteria were: (1) prospective study, (2) Duke or Von Reyn definition of IE, (3) definite IE, and (4) number of patients above 40. Quality was assigned as A, or excellent, with 4 points, B or good, with 2-3 points, and C, or suboptimal, with 0-1 points. Data was weighted for quality for SA and SV without affecting results statistical significance.

Statistical analysis

Data were extracted independently by two researchers (LS and CD) and collected on an Excel spreadsheet. Data were allocated to a decade according to the midpoint date for the time frame studied. For example if the time frame was 1979 to 1983, data was assigned to the 80s. Results are shown as mean +/- SD, percentages for each decade, and the 95% CI. Main variables studied were the frequency distribution of pathogens, patient age and gender, and in-hospital mortality. ANOVA and Chi2 test were used to compare studies by decades. Each group was compared to the rest using paired Students t-tests. Samples were weighted for size. Results from our own hospital were included in the last decade and weighted for size. Sensitivity analysis showed that subtracting this data did not affect results statistic significance. Moreover subtracting the biggest study by Murdoch et al. from the International Collaboration on Endocarditis did not affect statistical significance of results. Sub-analyses were performed for continent and IVDA. Correlation between IVDA and SA was performed using Spearman correlation test. Hospital-based studies and population-based studies were included. As both types of studies may be prone to bias (hospital-based studies to referral bias[22] and population-based studies to selection bias) hospital-based and population-based studies were analyzed separately. Sensitivity analyses were performed for size, single vs multi-center and quality without affecting significance of results. A p<0.05 was considered statistically significant. Analyses were performed using JMP version 10.0 (SAS Institute, Cary, NC, US).

Data were presented in a graph as mean (in green, centerline of diamond) and variance (size of diamond) for each variable studied in each decade, with standard deviations (blue). Each dot in a column represents a particular study percentage. N below decades represents total number of patients in each decade. Every patient included in each study was diagnosed with IE as described above.


Candidate studies included 24,415 articles identified in PubMed, 10,421 in Medline, and 4,528 in EMBASE; one hundred sixty studies met all inclusion criteria (see flow diagram in Figure 1). Of these, 142 were hospital-based, including a total of 23,606 patients (Table 1), and 18 were population-based, including a total of 3,477 patients (Table 2). Investigators (LS and CD) were in agreement on which articles were to be included (k=1).

Al-Tawfiq[37]54RMod DukeDef60684317722291995-08Saudi ArabiaB
Avanekar[39]600PMod DukeNR636722327103480-98USAB
Barrau[41]170PMod DukeDef657413187101134114-00FranceA
Bishara[43]252RMod DukePos62542432116251602387-96IsraelB
Bouramoue[45]32RVon ReynPos194176-89CongoB
Braun[47]261PVon Reyn/DukePos496918311023162880-99ChileB
Buchholtz[48]235PMod DukePos617022918121562502-05DenmarkB
Cecchii[51]147PMod DukeDef191882514102500-01ItalyA
Cetinkaya[52]189RMod Duke/Von ReynNR3666128565002074-99TurkeyB
Chen[55]178RVon ReynPos62392762579-91AustraliaB
Corral[60]550RMod DukePos5173441512584185-02SpainB
Couturier[61]66RDuke/Von ReynDef57652662051492-98FranceB
Di Salvo[63]178RDukeDef57755121132693-00FranceB
Dwyer[65]193RVon ReynPos51653926551092279-92AustraliaB
Fefer[68]108RDuke/Von ReynPos5756133171118113190-99IsraelB
Ferreiros[69]390PMod DukeDef59702825610112541601-02ArgentinaA
Gergaud[72]53RVon ReynPos6666111941115131783-90FranceB
Giannitsioti[73]195PMod DukePos646517211020102072200-04GreeceB
Gossius[74]46RVon ReynPos3720134201772-81NorwayB
Hermida Amej[81]87RMod DukeDef557644187823089-03SpainB
Hill[82]203PMod DukeDef6760311211171113400-04BelgiumA
Hricak[83]190PDuke/Von ReynPos1663302-06SlovakiaB
Hricak[83]339PDuke/Von ReynPos1574191-01SlovakiaB
Hricak[83]75PDuke/Von ReynPos151211084-90SlovakiaB
Hsu[84]315RMod DukePos51592265204895-03TaiwanB
Huang[85]72RMod DukePos58503543253019403-06TaiwanB
Jain[88]247RMod DukePos7157195451575396-03USAB
Kanafani[91]89RMod DukePos4864.202083221802086-01LebanonB
Kazanjian[92]60PPelletier/Von ReynNR62572715108528784-89USAB
Kim[94]56RVon ReynPos52711447542072375-87USA (HI)B
Knudsen[97]51PMod DukeNR587525318168166600-01DenmarkB
Knudsen[97]121PMod DukeNR64782525151592234505-06DenmarkB
Koegelenberg[98]60PDukePos38582103265016797-00South AfricaB
Leblebicioglu[102]112PMod DukePos4550352915161681700-04TurkeyB
Lederman[103]123RMod Von ReynNR4255233466610291072-84USAB
Letaief[105]440PMod DukePos3255121164502101791-00TunisiaB
Lien[106]72RPelletier/Von ReynProb55582133441801073-84NorwayC
Lopez-Dupla[108]120RMod DukePos51683324106131925690-04SpainB
Lupis[112]36RMod DukeDef545681158803-06ItalyB
Math[114]104PMod DukeDef2471775662602304-06IndiaA
Murdoch[120]2781PMod DukeDef5868311711101018102200-05MulticenterA
Nashmi[123]47RMod DukeDef32592411171326942193-03S. ArabiaB
Nunes[127]62PMod DukePos456321101036313101-08BrazilB
Olaison[129]161PDuke/Von ReynNR6050272357221041684-88SwedenB
Olds[130]43RVon ReynPos611717572485-89USAB
Pazdernik[133]117RMod DukeDef6073319713181911898-06Czech RepB
Peat[134]78RVon ReynPos5054215361242176-86NZB
Romero-Vivas[139]100RVon Reyn402330872477-82SpainC
Sandre[143]135RDuke/Von ReynPos6527410610113185-93CanadaB
Shively [148]16POtherN/A38196231888-89USAC
Slipczuk261RMod DukePos60494810720425151100-10USAB
Sucu[152]72RMod DukeDef4557171710436152904-07TurkeyB
Sy[154]273RMod DukePos55684319481523192096-06AustraliaB
Tariq[155]66RMod DukePos24675188248272897-01PakinstanB
Terpenning[156]154RVon ReynProb36269103221876-85USAB
Tornos[159]104PMod DukePos57703313141482601EuropeB
Tugcu[161]68RMod DukePos51592813132212505697-07TurkeyB
Verheul[163]141RVon ReynPos4574186866-91NetherlandsB
Vlessis[164]140RVon ReynPos57652159112282-92USAB
Von Reyn[165]104RVon ReynPos51253437542170-77USAB
Wells[168]102RVon ReynNR52642743345274979-86NZB
Witchitz[172]228NRVon ReynProb36981-88FranceB
Witchitz[172]257NRVon ReynProb3013992273-80FranceB
Wong[173]57RMod DukePos667728710122802-07NZB

Table 1. Characteristics of hospital-based studies included.

Frequency distribution for pathogens, male, in-hospital mortality and, IVDA and prosthetic valve are expressed as percentage of total. De=Design. Cert= Diagnosis certainty. SA= Staphylococcus aureus. SV Strepcococcus viridans. CNS= Coagulase-negative Staphylococcus. Ent= Enterococci. CN= Culture negative. Mort= In-hospital mortality. IVDA= Intravenous drug abuse IE. Prosthetic= Prosthetic valve IE. P= Prospective. R=Retrospective. Def= Definite. Pos= Possible. Prob= Probable. NR= Not reported. N/A= Not applicable.
Download CSV
AuthorNDeDefinitionCertIncidenceCase findAge   Male   SA   SV   CNS   Ent   Cn   Mort   IVDA   Prosth   YearCountryQuality
Benes[175]134PMod DukePos3.4cases/100K/yearMD report hospital6960301388348807-08Czech RepB
Benn[176]62RVon ReynNR27 cases/millon/yearD/c statistics55583421515851384-93DenmarkB
Correa de Sa[177]40PMod DukePos5.0 to 7.9 cases/100K/yearRegistry7150303020851801-06USAB
Delahaye[178]401PVon ReynPos22.4cases/millon/yearQuestionnaire5664182751092152290-91FranceB
Goulet[179]288PVon ReynPos18cases/millon/yearSurvey501237620101582-83FranceB
Griffin[180]37RVon ReynPos3.9 cases/millon/yearRegistry33356370-81USAC
Griffin[180]21RVon ReynPos3.3 cases/millon/yearRegistry384310060-69USAC
Hoen[181]390PDukeDef31 cases/million/yearSurvey607123166751661699FranceA
Hogevik[182]127P,RMod Von ReynPos6.2 cases/100K/yearMD report hospital693631226592371584-88SwedenB
King[183]75PPelletier/Von ReynPos1.7 cases/100K/yearMD report hospital48563525493171985-86USAB
Schnurr[185]70ROtherN/ANRRegistry and hospitand records61204577673-76ScotlandC
Scudeller[186]254PMod DukePos4.21 cases/100K/yearMD report hospital67671817191923204-08ItalyB
Smith[187]78ROtherNA16 cases/million/yearRegistry5618242069-72ScotlandC
Steckelberg[22]68NRMod Von ReynNR4.2 cases/100K/yearRegistry and hospital records294073122833570-87USAB
Tleyjeh[16]48PMod DukePos6.3-6.5 cases/100K/yearRegistry and hospital records6471294248062590-00USAB
Tleyjeh[16]34PMod DukePos5.0-7.0 cases/100K/yearRegistry and hospital records5771204715602980-90USAB
Tleyjeh[16]25PMod DukePos5.3 - 6.0 cases/100K/yearRegistry and hospital records61802844004470-79USAB
Van der Meer[188]406PVon ReynPos15 cases/million/yearSurvey52662040512072086-88NetherlaB
Whitby[189]71RVon ReynNRNRRegistry, MD report and medical records51681342491776-81UKB

Table 2. Characteristics of population-based studies included.

Frequency distribution for pathogens is expressed as percentage of total. De=Design. Cert= Diagnosis certainty. SA= Staphylococcus aureus. SV Strepcococcus viridans. CNS= Coagulase-negative Staphylococcus. Ent= Enterococci. CN= Culture negative. Mort= In-hospital mortality. IVDA= Intravenous drug abuse IE. Prosth= Prosthetic valve IE. P= Prospective. R=Retrospective. Def= Definite. Pos= Possible. NR= Not reported. N/A= Not applicable.
Download CSV

Hospital-based Studies

Among hospital-based studies, IE epidemiology changed over the last 5 decades (Figure 2). Patients were significantly older (Figure 2A; 1980s: mean age 45.3, CI 40.2- 50.5 vs 2000s: mean age 57.2, CI 54.7- 59.7, p<0.001), and more were men (Figure 2B; 1970s: 58.6%, CI 54.3- 63.0 vs 2000s: 66.3%, CI 63.6- 69.0, p<0.01). The percentage of IE cases occurring on prosthetic valves increased over time though with borderline statistical significance (Figure 2C; 1960s: 8.4%, CI -3.8- 20.5 vs 2000s: 22.9%, CI 19.1 - 26.7, p=0.05).

Figure 2. Epidemiology of Infective Endocarditis.

Figure shows age (A), male percentage (B) or prosthetic valve IE (C) of patients in each decade (mean in green, centerline of diamond) and variance (as size of diamond) plus standard deviation (blue). Each dot in column represents a particular study mean. N below decades represents total number of patients in each decade. A) IE patients are older in the last two decades. B) Male to female ration increased in the last decade. C) No significant changes were found on prosthetic valve IE. However a trend towards an increase can be seen. *= p<0.05; **=p<0.01; ***=p<0.001.

Changes in microbiology percentage over time are summarized in Figure 3 and shown in e- Figure 1 for individual organisms. There were significant increases in frequency distribution of Staphylococcus aureus (SA, Figure 4A) IE (1960s: 18.1% CI 9.4- 26.7 vs 2000s: 29.7%, CI 26.2- 33.3, p<0.05) and coagulase-negative staphylococcus (CNS, Figure 4B) IE (1960s: 2.4%, CI 0.8-5.5 vs 2000s: 10.0%, CI 8.6-11.3, p<0.01). Enterococcal IE percentage increased significantly over the last decade (Figure 4C, 1980s: 6.8%, CI 5.4- 8.2 vs 2000s: 10.5%, CI 8.9- 12.1, p<0.001) while culture negative IE decreased in that time period (Figure 4D, 1980s: 23.1%, CI 15.0- 31.3 vs 2000s: 14.2% CI 9.9- 18.2; p=0.01). Streptococcus viridans (SV) IE markedly decreased in percentage over time span of the study (Figure 4E, 1960s: 27.4%, CI 18.4-36.4 vs 2000s: 17.6%, CI 15.7-19.5, p<0.05).

Figure 3. Summary of Worldwide Microbiology of Infective Endocarditis.

Bars represent percentage of Staphylococcus aureus (SA) (light green), Streptococcus viridans (SV, dark green), enterococci (Entero, light blue), coagulase-negative staphylococcus (CNS, dark blue), and Culture negative (CN, white) endocarditis in each decade. *= p<0.05; **=p<0.01; ***=p<0.001.

Figure 4. Microbiology of Infective Endocarditis.

Figure shows percentage of Staphylococcus aureus (SA) IE (A), coagulase-negative staphylococcus (CNS, B), enterococci (C), Culture negative (D) and Streptococcus viridans (SV, E) of patients in each decade (mean in green, centerline of diamond) and variance (as size of diamond) plus standard deviation (blue). Each dot in column represents a particular study mean. N below decades represents total number of patients in each decade. A) SA increased in the last decade. B) CNS increased over time. C) enteroccoci increased in the last decade. D) Culture negative endocarditis decreased in the last decade. E) SV decreased over time. *= p<0.05; **=p<0.01; ***=p<0.001.

Subgroup analyses, by continent, were performed. The increase in overall SA frequency was driven by an increase in North America (Figure 5A; 1960s: 25.3%, CI 13.9- 36.6 vs 2000s: 52.4%, CI 42.4- 62.3, p=0.001). SA percentage in Europe remained stable over the last 4 decades (Figure 5B; 1970s: 25.1%, CI 18.2- 32.1 vs 2000s: 23.5%, CI 19.1- 28.0, p=0.70). No significant differences were found in SA IE frequency in Asia, Africa, Latin America, or Oceania.

Figure 5. Regional Differences for Staphylococcus Aureus and Intravenous Drug Abuse.

Figure shows percentage of Staphylococcus aureus (Staph, SA) IE in North America (A) or Europe (B) and intravenous drug abuse related IE in North America (C) and Europe (D), of patients in each decade (mean in green, centerline of diamond) and variance (as size of diamond) plus standard deviation (blue). N below decades represents total number of patients in each decade. A) SA increased markedly over last half century in North America B) No changes in SA were found in Europe. C) IVDA related IE frequency increased in North America. D) IVDA related IE percentage decreased in Europe in the last decade. *= p<0.05; **=p<0.01; ***=p<0.001.

Counterbalancing the increase in SA IE percentage in North America was a decrease in SV IE frequency (1970s: 33.5%, CI 25.8- 41.3 vs 2000s: 14.4%, CI 5.6- 23.2, p<0.01). SV IE frequency distribution also decreased significantly in Asia (1970s: 41.5%, CI 28.7- 54.4 vs 2000s: 10.1%, CI -8.9- 29.2, p<0.01) while in Europe there was a decrease that did not reach statistical significance (p=0.06). No significant changes were seen in Latin America and Oceania (p=0.9, p=0.32, respectively). Insufficient data were available from Africa for separate analysis.

Subgroup analyses for changes in IVDA IE percentage are shown in Figure 5. No significant changes were seen on a global basis. However, a significant increase in IVDA related IE frequency distribution was observed in North America in the last decade (Figure 5C; 1980s: 17.3%, CI 10.7- 23.9 vs 2000s: 50.7%, CI 28.5- 73.0, p<0.05). Conversely, we observed a significant decrease in IVDA related IE percentage in Europe in the last decade (Figure 5D; 1990s: 21.1%, CI 12.3- 29.8 vs 2000s: 6.8%, CI 3.5- 10.2, p<0.01). We found a positive correlation between SA IE and IVDA. Interestingly, this correlation lost strength in the last decade (1990s rs=0.82, p=0.001 vs 2000s rs=0.40 p=0.05; 1990s vs 2000s, Fisher r-to-z transformation, p<0.001). We further analyzed the studies that reported microbiology for the IVDA IE group. Twenty-five studies and 1288 patients were included in this sub-analysis. No significant temporal trends in IVDA IE microbiology were found. In this subset of patients, SA represented the main pathogen (1970s: 69.89 CI 31.40- 108.38, 1980s: 72.72 CI 57.98- 93.45, 1990s: 61.78 CI 47.87- 75.68 and 2000s: 65.99 CI 55.12- 76.86) and SV represented a small percentage of cases (1970s: 16.66 CI 3.87- 29.45, 1980s: 8.87 CI 2.79- 14.95, 1990s: 7.37 CI 3.57- 11.19, 2000s: 10.01 CI 7.21- 12.81).

In-hospital mortality rate due to IE decreased following the 1960s and remained stable thereafter (Figure 6; 1960s: 30.6%, CI 24.4- 36.8 vs 2000s: 19.7%, CI 17.8- 21.6, p=0.01). On subgroup analysis by continent, no regional differences were observed.

Figure 6. In-Hospital Mortality of Infectious Endocarditis.

Figure shows percentage of in-hospital mortality of Infectious Endocarditis in each decade (mean in green, centerline of diamond) and variance (as size of diamond) plus standard deviation (blue). Each dot in column represents a particular study mean. N below decades represents total number of patients in each decade. In-hospital mortality decreased after the 1960s and remained stable thereafter. ∗∗=p<0.01.

Population-based Studies

Among population-based studies, no significant trends were observed regarding IE microbiology as shown in Table 3 (SA p=0.82; SV p=0.14; enterococci p=0.33). These studies included populations in the US and Europe primarily. Only one study was from Asia. Of note, the majority of data from the US is from Olmstead County, Minnesota.

SA38 % [-1%-77%]22% [12%-31%]21% [15%-26%]21% [14%-27%]19% [13%-24%]0.82
SV43% [-9%-95%]37% [24%-50%]34% [27%-42%]23% [14%-31%]27% [19%-33%]0.14
Entero56% [-3%-14%]13% [8%-19%]8% [3%-13%]9% [5%-13%]0.33

Table 3. Microbiology of Infective Endocarditis from Population-based Studies.

Among population-based studies, no significant changes were observed regarding infectious endocarditis microbiology incidence over last five decades. Note that percentages are weighted by size and therefore sum of each decade may exceed 100%.
Download CSV

2000s data from Einstein Medical Center, Philadelphia, PA, US

We identified a total of 261 cases from 2000 to 2010 (Table 4). Mean age was 59 and 49% were male. In-hospital mortality rate was 25⋅3%. Prosthetic IE represented 10.7% and IVDA 14.6%. SA was the primary IE microorganism seen causing 48.3% of IE [25.3% Methicillin-sensitive Staphylococcus aureus (MSSA) and 23.0% Methicillin-resistant Staphylococcus aureus (MRSA)] while CNS was seen in 6.9% of the cases. Enterococcus was the IE etiology in 19.2% and SV 9.6%. Culture negative IE represented 3.8%. Removal of this data did not modify overall results.

Time frame2000-2010
In-hosp mort25.3%
Staph aureus48.3%
Strep viridans9.6%
Coag Neg Staph6.9%
Culture neg3.8%

Table 4. Data from Einstein Medical Center from 2000-2010.

Download CSV


The main finding of this study is that the epidemiology of IE has changed worldwide over the last half century. Furthermore, the observed changes in IE microbiology varied by continent. These findings stemmed from analyses of hospital-based reports. In a separately analyzed smaller group of population-based studies (most of them from the US), no consistent changes in IE microbiology frequency distribution over time were observed.

Most notably, the global percentage of SA IE has nearly doubled in the last five decades (18% in the 1960s to nearly 30% in the 2000s). When analyzed by continent this increase was largely due to an increased frequency of SA in North America (from 25% in the 1960s to 52% in the 2000s) with no significant change among reports from other continents. This finding has important implications as SA infections are associated with longer length of stay, higher death rates[23], increase hospitalizations[24], and elevated costs[24]. An increase in IVDA IE percentage in North America as compared to Europe may partially explain these changes in SA frequency distribution. However, the number of studies in the last decade in this analysis is small and therefore this finding should be studied further. Other potential contributors include increases in the elderly population[10], increased numbers of chronically-ill patients[25], increased contacts with the health-care system[26,27], and increasing use of intracardiac and vascular devices. Benito and colleagues[27] found a high percentage of health-care associated infections (related to catheters, dialysis, or immunosuppressive therapy) among US patients with native valve IE; SA was the most common organism isolated. Though the present study was not able to specifically track cardiac device implantation, another recent study found an increased prevalence of staphylococcal IE in these patients[28]. In absolute numbers Bor et al, reported an incidence of infective endocarditis in the US close to 40,000 cases/year [29]. Furthermore, at least when measured by ICD codes the total number of SA cases seems to be increasing in the US [15]. In addition, certain subgroups may behave differently; a well-designed population based study found that SA frequency has increased in Europe in patients without previously known valve disease[5]. It is important to clarify that changes in individual countries may not necessarily follow the trends at a continent level.

The present study also documents a substantial decline in the frequency of SV IE over the last five decades (27.4% in the 1960s to 17.6% in the 2000s). This finding was statistically significant for North America and Asia with a strong trend in Europe. Therefore, it appears that changes in the epidemiology of this organism are more widespread than for SA.

Paralleling the increase in SA IE frequency, there was also an increase in CNS IE percentage over time. It is known that CNS infections are often related to the use of intravascular catheters and prosthetic vascular grafts[30]. Thus, the rise in CNS IE may well be health-care related.

Enterococcal IE frequency increased in the last decade of the study. Enterococcal infections typically affect elderly patients and those with prior valvular damage, diabetes mellitus, indwelling catheters, or who are on hemodyalisis[31]. This finding is extremely important given the high prevalence of multidrug resistant enterococci and therefore the implications on treatment options. Lastly, culture negative endocarditis percentage decreased in the last decade. This is likely because of improved laboratory techniques and culture methods.

Worldwide, the present study found increases in age among IE patients. This has important implications for treatment and use of health care resources as elderly patients have more comorbidities and may be more prone to infection with certain organisms, such as enterococci. Consistent with the general perception[18], the present study found that in-hospital mortality rate of IE remains high with no significant decrease observed since the 1960s.

A limitation of the present study is the lack of individual patient level data. This data was not available from older studies and including it for only the last decades would have changed one bias for another one, without adding accuracy. Another limitation is that most of the findings come from hospital-based studies, whereas no significant changes were seen in the population based-studies over time. One possible explanation for this is a lack of power (18 population-based studies covering 3,477 patients vs 142 hospital-based studies covering 23,606 patients). Population-studies are also subject to sample bias: the population studied may not truly represent the general population. They can be subject to underreporting, as many times they rely on surveys. Moreover, population-studies of IE in the US are mainly from the Olmstead County, a population that is unlikely to represent the total US population. Hospital-based studies can suffer from referral bias as well, with sicker patients being referred to specialized centers. Thus, these results might not apply to community hospitals. However, Kanafani and colleagues[32] found only a slight difference between referred and non-referred patients, with higher SA IE in the non-referred patients. Thus, had this played a role in the present study, it would have likely decreased SA frequency. Therefore, it is unlikely to explain our findings. Finally, the definition of IE has changed over time, as well as culture quality, which could have caused heterogeneity in the cases included.


The present study represents the largest systematic review of IE epidemiology to date. Important findings include an increase in staphylococcal IE frequency over the last half-century, particularly in North America, and a worldwide decrease in SV IE percentage. In the last decade SA IE and enterococci IE frequencies have increased while culture negative IE has decreased. Patients with IE are getting older and the male to female ratio is increasing. Mortality has changed little in the last four decades.


Authors would like to thank Dr. Andrew Wang at Duke University for reviewing the list of included studies for completeness, and Drs. Yukiko Yanakama, Alexei Polishchuk and Julie Lai at Einstein Medical Center for translation assistance. All the authors had full access to all the data and take responsibility for the integrity of the data and the accuracy of the data analysis.

Author Contributions

Conceived and designed the experiments: LS JNC CD ARC GSP VF. Analyzed the data: LS JNC CD ARC GSP VF JY. Contributed reagents/materials/analysis tools: LS JNC CD ARC GSP VF. Wrote the manuscript: LS JNC CD ARC GSP VF.


  1. 1. Bayer AS (1993) Infective endocarditis. Clin Infect Dis 17: 312-321; quiz:
  2. 2. Moreillon P, Que YA (2004) Infective endocarditis. Lancet 363: 139-149. doi: PubMed: 14726169.
  3. 3. Verhagen DW, Hermanides J, Korevaar JC, Bossuyt PM, van den Brink RB et al. (2009) Health-related quality of life and posttraumatic stress disorder among survivors of left-sided native valve endocarditis. Clin Infect Dis 48: 1559-1565. doi: PubMed: 19392637.
  4. 4. Osler W (1885) The Gulstonian Lectures, on Malignant Endocarditis. Br Med J 1: 467-470. doi: PubMed: 20751186.
  5. 5. Duval X, Delahaye F, Alla F, Tattevin P, Obadia JF et al. (2012) Temporal trends in infective endocarditis in the context of prophylaxis guideline modifications: three successive population-based surveys. J Am Coll Cardiol 59: 1968-1976. doi: PubMed: 22624837.
  6. 6. Bannay A, Hoen B, Duval X, Obadia JF, Selton-Suty C et al. (2011) The impact of valve surgery on short- and long-term mortality in left-sided infective endocarditis: do differences in methodological approaches explain previous conflicting results? Eur Heart J 32: 2003-2015. doi: PubMed: 19208650.
  7. 7. Cabell CH, Heidenreich PA, Chu VH, Moore CM, Stryjewski ME et al. (2004) Increasing rates of cardiac device infections among Medicare beneficiaries: 1990-1999. Am Heart J 147: 582-586. doi: PubMed: 15077071.
  8. 8. Darouiche RO (2004) Treatment of infections associated with surgical implants. N Engl J Med 350: 1422-1429. doi: PubMed: 15070792.
  9. 9. McCarthy JT, Steckelberg JM (2000) Infective endocarditis in patients receiving long-term hemodialysis. Mayo Clin Proc 75: 1008-1014. doi: PubMed: 11040848.
  10. 10. Durante-Mangoni E, Bradley S, Selton-Suty C, Tripodi MF, Barsic B et al. (2008) Current features of infective endocarditis in elderly patients: results of the International Collaboration on Endocarditis Prospective Cohort Study. Arch Intern Med 168: 2095-2103. doi: PubMed: 18955638.
  11. 11. Martin GS, Mannino DM, Eaton S, Moss M (2003) The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 348: 1546-1554. doi: PubMed: 12700374.
  12. 12. Wisplinghoff H, Bischoff T, Tallent SM, Seifert H, Wenzel RP et al. (2004) Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis 39: 309-317. doi: PubMed: 15306996.
  13. 13. Fluit AC, Jones ME, Schmitz FJ, Acar J, Gupta R et al. (2000) Antimicrobial susceptibility and frequency of occurrence of clinical blood isolates in Europe from the SENTRY antimicrobial surveillance program, 1997 and 1998. Clin Infect Dis 30: 454-460. doi: PubMed: 10722427.
  14. 14. Fowler VG Jr., Miro JM, Hoen B, Cabell CH, Abrutyn E et al. (2005) Staphylococcus aureus endocarditis: a consequence of medical progress. JAMA 293: 3012-3021. doi: PubMed: 15972563.
  15. 15. Federspiel JJ, Stearns SC, Peppercorn AF, Chu VH, Fowler VG Jr. (2012) Increasing US rates of endocarditis with Staphylococcus aureus: 1999-2008. Arch Intern Med 172: 363-365. doi: PubMed: 22371926.
  16. 16. Tleyjeh IM, Steckelberg JM, Murad HS, Anavekar NS, Ghomrawi HM et al. (2005) Temporal trends in infective endocarditis: a population-based study in Olmsted County, Minnesota. JAMA 293: 3022-3028. doi: PubMed: 15972564.
  17. 17. Tleyjeh IM, Abdel-Latif A, Rahbi H, Scott CG, Bailey KR et al. (2007) A systematic review of population-based studies of infective endocarditis. Chest 132: 1025-1035. doi: PubMed: 17873196.
  18. 18. Wang A (2012) The changing epidemiology of infective endocarditis: the paradox of prophylaxis in the current and future eras. J Am Coll Cardiol 59: 1977-1978. doi: PubMed: 22624838.
  19. 19. Li JS, Sexton DJ, Mick N, Nettles R, Fowler VG Jr. et al. (2000) Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis 30: 633-638. doi: PubMed: 10770721.
  20. 20. Khan KS, Kunz R, Kleijnen J, Antes G (2003) Systematic reviews to support evidence-based medicine: how to review and apply findings of healthcare research. London: Royal Society Medical Press.
  21. 21. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD et al. (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-Analysis of Observational Studies in Epidemiology (MOOSE). Group - JAMA 283: 2008-2012.
  22. 22. Steckelberg JM, Melton LJ 3rd, Ilstrup DM, Rouse MS, Wilson WR (1990) Influence of referral bias on the apparent clinical spectrum of infective endocarditis. Am J Med 88: 582-588. doi: PubMed: 2346159.
  23. 23. Rubin RJ, Harrington CA, Poon A, Dietrich K, Greene JA et al. (1999) The economic impact of Staphylococcus aureus infection in New York City hospitals. Emerg Infect Dis 5: 9-17. doi: PubMed: 10081667.
  24. 24. Noskin GA, Rubin RJ, Schentag JJ, Kluytmans J, Hedblom EC et al. (2005) The burden of Staphylococcus aureus infections on hospitals in the United States: an analysis of the 2000 and 2001 Nationwide Inpatient Sample Database. Arch Intern Med 165: 1756-1761. doi: PubMed: 16087824.
  25. 25. Hoffman C, Rice D, Sung HY (1996) Persons with chronic conditions. Their prevalence and costs. JAMA 276: 1473-1479. doi: PubMed: 8903258.
  26. 26. Friedman ND, Kaye KS, Stout JE, McGarry SA, Trivette SL et al. (2002) Health care--associated bloodstream infections in adults: a reason to change the accepted definition of community-acquired infections. Ann Intern Med 137: 791-797. doi: PubMed: 12435215.
  27. 27. Benito N, Miró JM, de Lazzari E, Cabell CH, del Río A et al. (2009) Health care-associated native valve endocarditis: importance of non-nosocomial acquisition. Ann Intern Med 150: 586-594. doi: PubMed: 19414837.
  28. 28. Athan E, Chu VH, Tattevin P, Selton-Suty C, Jones P et al. (2012) Clinical characteristics and outcome of infective endocarditis involving implantable cardiac devices. JAMA 307: 1727-1735. doi: PubMed: 22535857.
  29. 29. Bor DH, Woolhandler S, Nardin R, Brusch J, Himmelstein DU (2013) Infective endocarditis in the U.S., 1998-2009: a nationwide study. PLOS ONE 8: e60033. doi: PubMed: 23527296.
  30. 30. Rogers KL, Fey PD, Rupp ME (2009) Coagulase-negative staphylococcal infections. Infect Dis Clin North Am 23: 73-98. doi: PubMed: 19135917.
  31. 31. Munita JM, Arias CA, Murray BE (2012) Enterococcal endocarditis: can we win the war? Curr Infect Dis Rep 14: 339-349. doi: PubMed: 22661339.
  32. 32. Kanafani ZA, Kanj SS, Cabell CH, Cecchi E, de Oliveira Ramos A et al. (2010) Revisiting the effect of referral bias on the clinical spectrum of infective endocarditis in adults. Eur J Clin Microbiol Infect Dis 29: 1203-1210. doi: PubMed: 20549531.
  33. 33. Aguero ME, Escobar E, Aguayo J (1982) Infectious endocarditis: study of 32 cases. Rev Med Chil 110: 133-138. PubMed: 7156560.
  34. 34. Groupe d'enquête de l'Association pour l'étude et la prévention de l'endocardite infectieuse (2003) Variations of the profile of infective endocarditis in France. Results of an epidemiologic survey carried out during a year. Arch Mal Coeur Vaiss 96: 111-120. PubMed: 14626733.
  35. 35. Ako J, Ikari Y, Hatori M, Hara K, Ouchi Y (2003) Changing spectrum of infective endocarditis: review of 194 episodes over 20 years. Circ J 67: 3-7. doi: PubMed: 12520142.
  36. 36. Allal J, Thomas P, Rossi F, Poupet JY, Petitalot JP et al. (1985) Current aspects of infectious endocarditis. Review of 101 cases. Ann Med Interne (Paris) 136: 91-96.
  37. 37. Al-Tawfiq JA, Sufi I (2009) Infective endocarditis at a hospital in Saudi Arabia: epidemiology, bacterial pathogens and outcome. Ann Saudi Med 29: 433-436. doi: PubMed: 19847079.
  38. 38. Auger P, Marquis G, Dyrda I, Martineau JP, Solymoss CB (1981) Infective endocarditis update experience from a heart hospital. Acta Cardiol 36: 105-123. PubMed: 6974938.
  39. 39. Anavekar NS, Tleyjeh IM, Mirzoyev Z, Steckelberg JM, Haddad C et al. (2007) Impact of prior antiplatelet therapy on risk of embolism in infective endocarditis. Clin Infect Dis 44: 1180-1186. doi: PubMed: 17407036.
  40. 40. Bailey IK, Richards JG (1975) Infective endocarditis in a Sydney teaching hospital--1962-1971. Aust N Z J Med 5: 413-420. doi: PubMed: 1061541.
  41. 41. Barrau K, Boulamery A, Imbert G, Casalta JP, Habib G et al. (2004) Causative organisms of infective endocarditis according to host status. Clin Microbiol Infect 10: 302-308. doi: PubMed: 15059118.
  42. 42. Bennis A, Zahraoui M, Azzouzi L, Soulami S, Mehadji BA et al. (1995) Bacterial endocarditis in Morocco. Ann Cardiol Angeiol (Paris) 44: 339-344.
  43. 43. Bishara J, Leibovici L, Gartman-Israel D, Sagie A, Kazakov A et al. (2001) Long-term outcome of infective endocarditis: the impact of early surgical intervention. Clin Infect Dis 33: 1636-1643. doi: PubMed: 11595978.
  44. 44. Borer A, Riesenberg K, Uriel N, Gilad J, Porath A et al. (1998) Infective endocarditis in a tertiary-care hospital in southern Israel. Public Health Rev 26: 317-330. PubMed: 10641529.
  45. 45. Bouramoué C, Azika-Mbiambina ME (1990) Infectious endocarditis in the University Hospital Center of Brazzaville. A study of 32 cases. Arch Mal Coeur Vaiss 83: 2053-2059. PubMed: 2126713.
  46. 46. Bouza E, Menasalvas A, Munoz P, Vasallo FJ, del Mar Moreno M et al. (2001) Infective endocarditis--a prospective study at the end of the twentieth century: new predisposing conditions, new etiologic agents, and still a high mortality. Medicine (Baltimore) 80: 298-307. doi:
  47. 47. Braun S, Escalona A, Chamorro G, Corbalán R, Pérez C et al. (2000) Infective endocarditis: short and long-term results in 261 cases managed by a multidisciplinary approach. Rev Med Chil 128: 708-720. PubMed: 11050831.
  48. 48. Buchholtz K, Larsen CT, Hassager C, Bruun NE (2009) In infectious endocarditis patients mortality is highly related to kidney function at time of diagnosis: a prospective observational cohort study of 231 cases. Eur J Intern Med 20: 407-410. doi: PubMed: 19524184.
  49. 49. Cabell CH, Jollis JG, Peterson GE, Corey GR, Anderson DJ et al. (2002) Changing patient characteristics and the effect on mortality in endocarditis. Arch Intern Med 162: 90-94. doi: PubMed: 11784225.
  50. 50. Casabe JH, Hershson A, Ramos M, Barisani J, Pellegrini C, Varini S (1996) Endocarditis infecciosa en la República Argentina. Complicaciones y mortalidad. Rev Argent Cardiol 64: 39-45.
  51. 51. Cecchi E, Forno D, Imazio M, Migliardi A, Gnavi R et al. (2004) New trends in the epidemiological and clinical features of infective endocarditis: results of a multicenter prospective study. Ital Heart J 5: 249-256. PubMed: 15185882.
  52. 52. Cetinkaya Y, Akova M, Akalin HE, Aşçioğlu S, Hayran M et al. (2001) A retrospective review of 228 episodes of infective endocarditis where rheumatic valvular disease is still common. Int J Antimicrob Agents 18: 1-7. doi: PubMed: 11463520.
  53. 53. Chao TH, Li YH, Tsai WC, Tsai LM, Lin LJ et al. (1999) Prognostic determinants of infective endocarditis in the 1990s. J Formos Med Assoc 98: 474-479. PubMed: 10462995.
  54. 54. Chen CH, Lo MC, Hwang KL, Liu CE, Young TG (2001) Infective endocarditis with neurologic complications: 10-year experience. J Microbiol Immunol Infect 34: 119-124. PubMed: 11456357.
  55. 55. Chen SC, Dwyer DE, Sorrell TC (1992) A comparison of hospital and community-acquired infective endocarditis. Am J Cardiol 70: 1449-1452. doi: PubMed: 1442617.
  56. 56. Cheng JJ, Ko YL, Chang SC, Lien WP, Tseng YZ et al. (1989) Retrospective analysis of 97 patients with infective endocarditis seen over the past 8 years. Taiwan Yi Xue Hui Za Zhi 88: 213-217. PubMed: 2794919.
  57. 57. Choudhury R, Grover A, Varma J, Khattri HN, Anand IS et al. (1992) Active infective endocarditis observed in an Indian hospital 1981-1991. Am J Cardiol 70: 1453-1458. doi: PubMed: 1442618.
  58. 58. Chu J, Wilkins G, Williams M (2004) Review of 65 cases of infective endocarditis in Dunedin Public Hospital. N Z Med J 117: U1021. PubMed: 15475991.
  59. 59. Cicalini S, Puro V, Angeletti C, Chinello P, Macrì G et al. (2006) Profile of infective endocarditis in a referral hospital over the last 24 years. J Infect 52: 140-146. doi: PubMed: 16442439.
  60. 60. Corral I, Martín-Dávila P, Fortún J, Navas E, Centella T et al. (2007) Trends in neurological complications of endocarditis. J Neurol 254: 1253-1259. doi: PubMed: 17260173.
  61. 61. Couturier F, Hansmann Y, Descampeaux C, Christmann D (2000) Epidemiologie des endocardites infectieuses. Etude realisee sur 66 cas d´endocardites infectieuses recensees entre 1992 et 1998 dans un service de medecine interne et de maladies infectieuses et tropicales. Med Mal Infect 30: 162-168. doi:
  62. 62. Deprèle C, Berthelot P, Lemetayer F, Comtet C, Fresard A et al. (2004) Risk factors for systemic emboli in infective endocarditis. Clin Microbiol Infect 10: 46-53. doi: PubMed: 14706086.
  63. 63. Di Salvo G, Habib G, Pergola V, Avierinos JF, Philip E et al. (2001) Echocardiography predicts embolic events in infective endocarditis. J Am Coll Cardiol 37: 1069-1076. doi: PubMed: 11263610.
  64. 64. Durack DT, Lukes AS, Bright DK (1994) New criteria for diagnosis of infective endocarditis: utilization of specific echocardiographic findings. Duke Endocarditis Service. Am J Med 96: 200-209. doi: PubMed: 8154507.
  65. 65. Dwyer DE, Chen SC, Wright EJ, Crimmins D, Collignon PJ et al. (1994) Hospital practices influence the pattern of infective endocarditis. Med J Aust 160: 708-716. 8202007.
  66. 66. Dyson C, Barnes RA, Harrison GA (1999) Infective endocarditis: an epidemiological review of 128 episodes. J Infect 38: 87-93. doi: PubMed: 10342647.
  67. 67. Fedorova TA, Iakovlev VN, Levina ON, Semenko NA, Roitman AP et al. (2008) Specific features of the clincal course of infectious endocarditis in a multi-field hospital. Klin Med (Mosk) 86: 62-66.
  68. 68. Fefer P, Raveh D, Rudensky B, Schlesinger Y, Yinnon AM (2002) Changing epidemiology of infective endocarditis: a retrospective survey of 108 cases, 1990-1999. Eur J Clin Microbiol Infect Dis 21: 432-437. doi: PubMed: 12111598.
  69. 69. Ferreiros E, Nacinovich F, Casabé JH, Modenesi JC, Swieszkowski S et al. (2006) Epidemiologic, clinical, and microbiologic profile of infective endocarditis in Argentina: a national survey. The Endocarditis Infecciosa en la Republica Argentina-2 (EIRA-2) Study. Am Heart J 151: 545-552. doi: PubMed: 16442929.
  70. 70. Finland M, Barnes MW (1970) Changing etiology of bacterial endocarditis in the antibacterial era. Experiences at Boston City Hospital 1933-1965. Ann Intern Med 72: 341-348.
  71. 71. Garvey GJ, Neu HC (1978) Infective endocarditis--an evolving disease. A review of endocarditis at the Columbia-Presbyterian Medical Center, 1968-1973. Medicine (Baltimore) 57: 105-127.
  72. 72. Gergaud JM, Breux JP, Grollier G, Roblot P, Becq-Giraudon B (1994) Current aspects of infectious endocarditis. Apropos of 53 cases. Ann Med Interne (Paris) 145: 163-167.
  73. 73. Giannitsioti E, Skiadas I, Antoniadou A, Tsiodras S, Kanavos K et al. (2007) Nosocomial vs. community-acquired infective endocarditis in Greece: changing epidemiological profile and mortality risk. Clin Microbiol Infect 13: 763-769. doi: PubMed: 17488327.
  74. 74. Gossius G, Gunnes P, Rasmussen K (1985) Ten years of infective endocarditis: a clinicopathologic study. Acta Med Scand 217: 171-179. PubMed: 3993432.
  75. 75. Gotsman I, Meirovitz A, Meizlish N, Gotsman M, Lotan C et al. (2007) Clinical and echocardiographic predictors of morbidity and mortality in infective endocarditis: the significance of vegetation size. Isr Med Assoc J 9: 365-369. PubMed: 17591374.
  76. 76. Gracey M, Rountree PM (1968) Bacterial endocarditis in a Sydney hospital from 1960 to 1965. Med J Aust 1: 984-988. PubMed: 5660295.
  77. 77. Haddy RI, Westveer D, Gordon RC (1981) Bacterial endocarditis in the community hospital. J Fam Pract 13: 807-811. PubMed: 6796642.
  78. 78. Hammami N, Mezghani S, Znazen A, Rhimi F, Kassis M et al. (2006) Bacteriological profile of infectious endocarditis in the area of Sfax (Tunisia). Arch Mal Coeur Vaiss 99: 29-32.
  79. 79. Heiro M, Helenius H, Mäkilä S, Hohenthal U, Savunen T et al. (2006) Infective endocarditis in a Finnish teaching hospital: a study on 326 episodes treated during 1980-2004. Heart 92: 1457-1462. doi: PubMed: 16644858.
  80. 80. Heper G, Yorukoglu Y (2002) Clinical, bacteriologic and echocardiographic evaluation of infective endocarditis in Ankara, Turkey. Angiology 53: 191-197. doi: PubMed: 11952110.
  81. 81. Hermida Ameijeiras A, López Rodríguez R, Rodríguez Framil M, Lado Lado F (2007) Infective endocarditis in an internal medicine ward. Rev Med Chil 135: 11-16. PubMed: 17369978.
  82. 82. Hill EE, Herijgers P, Claus P, Vanderschueren S, Herregods MC et al. (2007) Infective endocarditis: changing epidemiology and predictors of 6-month mortality: a prospective cohort study. Eur Heart J 28: 196-203. PubMed: 17158121.
  83. 83. Hricak V, Liska B, Kovackova J, Mikusova J, Fischer V et al. (2007) Trends in risk factors and etiology of 606 cases of infective endocarditis over 23 years (1984-2006) in slovakia. J Chemother 19: 198-202. PubMed: 17434830.
  84. 84. Hsu CN, Wang JY, Tseng CD, Hwang JJ, Hsueh PR et al. (2006) Clinical features and predictors for mortality in patients with infective endocarditis at a university hospital in Taiwan from 1995 to 2003. Epidemiol Infect 134: 589-597. doi: PubMed: 16238819.
  85. 85. Huang TY, Tseng HK, Liu CP, Lee CM (2009) Comparison of the clinical manifestations of infective endocarditis between elderly and young patients - a 3-year study. J Microbiol Immunol Infect 42: 154-159. PubMed: 19597648.
  86. 86. Husebye T, Smith G, von der Lippe E, Jacobsen D, Fjeld NB (1998) Infectious endocarditis at Ulleval hospital 1988-94. Echocardiographic investigation. Tidsskr nor Laegeforen 118: 222-225. PubMed: 9485616.
  87. 87. Jaffe WM, Morgan DE, Pearlman AS, Otto CM (1990) Infective endocarditis, 1983-1988: echocardiographic findings and factors influencing morbidity and mortality. J Am Coll Cardiol 15: 1227-1233. doi: PubMed: 2184183.
  88. 88. Jain V, Yang MH, Kovacicova-Lezcano G, Juhle LS, Bolger AF et al. (2008) Infective endocarditis in an urban medical center: association of individual drugs with valvular involvement. J Infect 57: 132-138. doi: PubMed: 18597851.
  89. 89. Jalal S, Khan KA, Alai MS, Jan V, Iqbal K et al. (1998) Clinical spectrum of infective endocarditis: 15 years experience. Indian Heart J 50: 516-519. PubMed: 10052275.
  90. 90. Julander I (1987) Septicemia and endocarditis, 1965-1980, in a Swedish university hospital for infectious diseases. Infection 15: 177-183. doi: PubMed: 3610322.
  91. 91. Kanafani ZA, Mahfouz TH, Kanj SS (2002) Infective endocarditis at a tertiary care centre in Lebanon: predominance of streptococcal infection. J Infect 45: 152-159. doi: PubMed: 12387770.
  92. 92. Kazanjian P (1993) Infective endocarditis: Review of 60 cases treated in community hospitals. Infect Dis Clin Pract 2: 41-46. doi:
  93. 93. Khanal B, Harish BN, Sethuraman KR, Srinivasan S (2002) Infective endocarditis: report of a prospective study in an Indian hospital. Trop Doct 32: 83-85. PubMed: 11931207.
  94. 94. Kim EL, Ching DL, Pien FD (1990) Bacterial endocarditis at a small community hospital. Am J Med Sci 299: 87-93. doi: PubMed: 2301455.
  95. 95. King JW, Shehane RR, Lierl J (1986) Infectious endocarditis at three hospitals in the same city: two study periods a decade apart. South Med J 79: 151-158. doi: PubMed: 3945844.
  96. 96. Kiwan YA, Hayat N, Vijayaraghavan DG, Das Chugh T, Khan N et al. (1990) Infective endocarditis: a prospective study of 60 consecutive cases. Mater Med Pol 22: 173-175. PubMed: 2132422.
  97. 97. Knudsen JB, Fuursted K, Petersen E, Wierup P, Mølgaard H et al. (2009) Infective endocarditis: a continuous challenge. The recent experience of a European tertiary center. J Heart Valve Dis 18: 386-394. PubMed: 19852142.
  98. 98. Koegelenberg CF, Doubell AF, Orth H, Reuter H (2003) Infective endocarditis in the Western Cape Province of South Africa: a three-year prospective study. QJM 96: 217-225. doi: PubMed: 12615986.
  99. 99. Koga Y, Shibata J, Yamasaki T, Ohkita Y, Toshima H (1985) Medical management of infective endocarditis; limitations and indication for surgery. Jpn Circ J 49: 535-544. doi: PubMed: 4021066.
  100. 100. Krecki R, Drozdz J, Ibata G, Lipiec P, Ostrowski S et al. (2007) Clinical profile, prognosis and treatment of patients with infective endocarditis--a 14-year follow-up study. Pol Arch Med Wewn 117: 512-520.
  101. 101. Kurland S, Enghoff E, Landelius J, Nyström SO, Hambraeus A et al. (1999) A 10-year retrospective study of infective endocarditis at a university hospital with special regard to the timing of surgical evaluation in S. viridans endocarditis. Scand J Infect Dis 31: 87-91. doi: PubMed: 10381225.
  102. 102. Leblebicioglu H, Yilmaz H, Tasova Y, Alp E, Saba R et al. (2006) Characteristics and analysis of risk factors for mortality in infective endocarditis. Eur J Epidemiol 21: 25-31. doi: PubMed: 16450203.
  103. 103. Lederman MM, Sprague L, Wallis RS, Ellner JJ (1992) Duration of fever during treatment of infective endocarditis. Medicine (Baltimore) 71: 52-57. PubMed: 1549059.
  104. 104. Leitersdorf E, Friedman G, Gozal D, Appelbaum A, Sacks T (1983) Infective endocarditis in Jerusalem. A comparative analysis of native and prosthetic valve endocarditis. Isr J Med Sci 19: 491-494. PubMed: 6862853.
  105. 105. Letaief A, Boughzala E, Kaabia N, Ernez S, Abid F et al. (2007) Epidemiology of infective endocarditis in Tunisia: a 10-year multicenter retrospective study. Int J Infect Dis 11: 430-433. doi: PubMed: 17331773.
  106. 106. Lien EA, Solberg CO, Kalager T (1988) Infective endocarditis 1973-1984 at the Bergen University Hospital: clinical feature, treatment and prognosis. Scand J Infect Dis 20: 239-246. doi: PubMed: 3406663.
  107. 107. Lode H, Harnoss CM, Wagner J, Biamino G, Schröder R (1982) Infectious endocarditis: clinical findings, therapy and course in 103 patients. Dtsch Med Wochenschr 107: 967-974. doi: PubMed: 7084062.
  108. 108. López-Dupla M, Hernández S, Olona M, Mercé J, Lorenzo A et al. (2006) Clinical characteristics and outcome of infective endocarditis in individuals of the general population managed at a teaching hospital without cardiac surgery facilities. Study of 120 cases. Rev Esp Cardiol 59: 1131-1139. doi: PubMed: 17144988.
  109. 109. Lou XF, Yang DY, Liu ZY, Wang HL, Li TS (2009) Clinical analysis of 120 cases of infective endocarditis. Zhonghua Nei Ke Za Zhi 48: 35-38. PubMed: 19484975.
  110. 110. Loupa C, Mavroidi N, Boutsikakis I, Paniara O, Deligarou O et al. (2004) Infective endocarditis in Greece: a changing profile. Epidemiological, microbiological and therapeutic data. Clin Microbiol Infect 10: 556-561. doi: PubMed: 15191385.
  111. 111. Lowes JA, Hamer J, Williams G, Houang E, Tabaqchali S et al. (1980) 10 Years of infective endocarditis at St. Bartholomew's Hospital: analysis of clinical features and treatment in relation to prognosis and mortality. Lancet 1: 133-136. PubMed: 6101466.
  112. 112. Lupis F, Giordano S, Pampinella D, Scarlata F, Romano A (2009) Infective endocarditis: review of 36 cases. Infez Med 17: 159-163. PubMed: 19838087.
  113. 113. Manzano MC, Vilacosta I, San Román JA, Aragoncillo P, Sarriá C et al. (2007) Acute coronary syndrome in infective endocarditis. Rev Esp Cardiol 60: 24-31. doi: PubMed: 17288952.
  114. 114. Math RS, Sharma G, Kothari SS, Kalaivani M, Saxena A et al. (2011) Prospective study of infective endocarditis from a developing country. Am Heart J 162: 633-638. doi: PubMed: 21982654.
  115. 115. Souto Meirino CA, Cotter Lemus LE, Assad Gutierrez J, Anorve Gallardo A, Rosete Suarez G (1997) [Infectious endocarditis at the National Institute of Cardiology "Ignacio Chavez". Five year's experience (1990-1994)]. Arch Inst Cardiol Mex 67: 46-50.
  116. 116. Mesa JM, Larrea JL, Oliver J, Cortina JM, Moreno I et al. (1990) Infective endocarditis. Medicosurgical experience in a series of 137 patients. Rev Esp Cardiol 43: 142-152. PubMed: 2333399.
  117. 117. Mills J, Utley J, Abbott J (1974) Heart failure in infective endocarditis: predisposing factors, course, and treatment. Chest 66: 151-157. doi: PubMed: 4852232.
  118. 118. Morelli S, De Marzio P, Voci P, Troisi G (1994) Infective endocarditis. Recent progress in its epidemiology, clinical picture and therapy. Comments on cases. Recenti Prog Med 85: 368-374. PubMed: 8079037.
  119. 119. Mouly S, Ruimy R, Launay O, Arnoult F, Brochet E et al. (2002) The changing clinical aspects of infective endocarditis: descriptive review of 90 episodes in a French teaching hospital and risk factors for death. J Infect 45: 246-256. doi: PubMed: 12423613.
  120. 120. Murdoch DR, Corey GR, Hoen B, Miró JM, Fowler VG Jr. et al. (2009) Clinical presentation, etiology, and outcome of infective endocarditis in the 21st century: the International Collaboration on Endocarditis-Prospective Cohort Study. Arch Intern Med 169: 463-473. doi: PubMed: 19273776.
  121. 121. Nadji G, Goissen T, Brahim A, Coviaux F, Lorgeron N et al. (2008) Impact of early surgery on 6-month outcome in acute infective endocarditis. Int J Cardiol 129: 227-232. doi: PubMed: 17999936.
  122. 122. Nakamura K, Koyanagi H, Hirosawa K (1982) Spectrum of the infective endocarditis in the past five years. Jpn Circ J 46: 352-361. doi: PubMed: 6896350.
  123. 123. Nashmi A, Memish ZA (2007) Infective endocarditis at a tertiary care centre in Saudi Arabia: review of 47 cases over 10 years. East Mediterr Health J 13: 64-71. PubMed: 17546907.
  124. 124. Netzer RO, Zollinger E, Seiler C, Cerny A (2000) Infective endocarditis: clinical spectrum, presentation and outcome. An analysis of 212 cases 1980-1995. Heart 84: 25-30. doi: PubMed: 10862581.
  125. 125. Nigro FS, Buonopane G, Giglio S, Maio P, Matarazzo M et al. (2001) Infective endocarditis: a retrospective analysis of inpatient cases. Infez Med 9: 232-236. PubMed: 12087211.
  126. 126. Nihoyannopoulos P, Oakley CM, Exadactylos N, Ribeiro P, Westaby S et al. (1985) Duration of symptoms and the effects of a more aggressive surgical policy: two factors affecting prognosis of infective endocarditis. Eur Heart J 6: 380-390. PubMed: 4043095.
  127. 127. Nunes MC, Gelape CL, Ferrari TC (2010) Profile of infective endocarditis at a tertiary care center in Brazil during a seven-year period: prognostic factors and in-hospital outcome. Int J Infect Dis 14: e394-e398. doi: PubMed: 19800277.
  128. 128. Okada K, Uchida Y, Sawae Y (1998) Infective endocarditis--a review of 21 cases in last 10 years. Fukuoka Igaku Zasshi 89: 34-43. PubMed: 9549176.
  129. 129. Olaison L, Hogevik H (1996) Comparison of the von Reyn and Duke criteria for the diagnosis of infective endocarditis: a critical analysis of 161 episodes. Scand J Infect Dis 28: 399-406. doi: PubMed: 8893406.
  130. 130. Olds J (1991) Infective endocarditis in Iowa. Iowa Med 81: 218-221. PubMed: 1869427.
  131. 131. Expósito Ordóñez E, de la Morena Valenzuela G, Gómez Gómez J, Ruipérez Abizanda JA, Sánchez Villanueva JG et al. (1998) Epidemiological changes in infectious endocarditis. A prospective study, 1992-96. An Med Interna 15: 642-646. PubMed: 9972598.
  132. 132. Pachirat O, Chetchotisakd P, Klungboonkrong V, Taweesangsuksakul P, Tantisirin C et al. (2002) Infective endocarditis: prevalence, characteristics and mortality in Khon Kaen, 1990-1999. J Med Assoc Thai 85: 1-10. PubMed: 12075707.
  133. 133. Pazdernik M, Baddour LM, Pelouch R (2009) Infective endocarditis in the Czech Republic: eight years of experience at one of the country's largest medical centers. J Heart Valve Dis 18: 395-400. PubMed: 19852143.
  134. 134. Peat EB, Lang SD (1989) Infective endocarditis in a racially mixed community: a 10 year review of 78 cases. N Z Med J 102: 33-36. PubMed: 2739964.
  135. 135. Pelletier LL Jr., Petersdorf RG (1977) Infective endocarditis: a review of 125 cases from the University of Washington Hospitals, 1963-72. Medicine (Baltimore) 56: 287-313. PubMed: 875718.
  136. 136. Proença R, Serrano A, Martins T, Machado J, Maltez F et al. (1999) Infective endocarditis. Acta Med Port 12: 381-386. PubMed: 10892441.
  137. 137. Quenzer RW, Edwards LD, Levin S (1976) A comparative study of 48 host valve and 24 prosthetic valve endocarditis cases. Am Heart J 92: 15-22. doi: PubMed: 961575.
  138. 138. Roca B, Marco JM (2007) Presentation and outcome of infective endocarditis in Spain: a retrospective study. Int J Infect Dis 11: 198-203. doi: PubMed: 16797198.
  139. 139. Romero-Vivas J, Romero-Vivas F, Bouza E, Martinez-Beltran J, Rodriguez-Creixems M et al. (1985) Infectious endocarditis. 5 years' experience. Med Clin (Barc) 84: 637-642.
  140. 140. Rostagno C, Rosso G, Puggelli F, Gelsomino S, Braconi L, et al. (2010) Active infective endocarditis: Clinical characteristics and factors related to hospital mortality. Cardiol J 17: 566-573.
  141. 141. Ruiz Júnior E, Schirmbeck T, Figueiredo LT (2000) A study of infectious endocarditis in Ribeirao Preto, SP-Brazil. Analysis of cases occurring between 1992 and 1997. Arq Bras Cardiol 74: 217-231. PubMed: 10951825.
  142. 142. Sanabria TJ, Alpert JS, Goldberg R, Pape LA, Cheeseman SH (1990) Increasing frequency of staphylococcal infective endocarditis. Experience at a university hospital, 1981 through 1988. Arch Intern Med 150: 1305-1309. doi: PubMed: 2353863.
  143. 143. Sandre RM, Shafran SD (1996) Infective endocarditis: review of 135 cases over 9 years. Clin Infect Dis 22: 276-286. doi: PubMed: 8838184.
  144. 144. Issa VS, Fabri J Jr., Pomerantzeff PM, Grinberg M, Pereira-Barreto AC et al. (2003) Duration of symptoms in patients with infective endocarditis. Int J Cardiol 89: 63-70. doi: PubMed: 12727006.
  145. 145. Seibaek MB, Olsen E, Høier-Madsen K, Hansen PF (1994) Bacterial endocarditis at a county hospital department, 1983-1992. Prognosis in relation to bacteriology, disease localization and treatment. Ugeskr Laeger 156: 6028-6032. PubMed: 7992444.
  146. 146. Sekido M, Takano T, Takayama M, Hayakawa H (1999) Survey of infective endocarditis in the last 10 years: analysis of clinical, microbiological and therapeutic features. J Cardiol 33: 209-215. PubMed: 10225203.
  147. 147. Shinebourne EA, Cripps CM, Hayward GW, Shooter RA (1969) Bacterial endocarditis 1956-1965: analysis of clinical features and treatment in relation to prognosis and mortality. Br Heart J 31: 536-542. doi: PubMed: 5351286.
  148. 148. Shively BK, Gurule FT, Roldan CA, Leggett JH, Schiller NB (1991) Diagnostic value of transesophageal compared with transthoracic echocardiography in infective endocarditis. J Am Coll Cardiol 18: 391-397. doi: PubMed: 1856406.
  149. 149. Siddiq S, Missri J, Silverman DI (1996) Endocarditis in an urban hospital in the 1990s. Arch Intern Med 156: 2454-2458. doi: PubMed: 8944738.
  150. 150. Singham KT, Anuar M, Puthucheary SD (1980) Infective endocarditis 1968-1977: an Asian experience. Ann Acad Med Singapore 9: 435-439. PubMed: 7247329.
  151. 151. Strate M, Nielsen JS (1987) Infectious endocarditis. A retrospective analysis of 34 cases. Ugeskr Laeger 149: 3031-3033. PubMed: 3433500.
  152. 152. Sucu M, Davutoğlu V, Ozer O, Aksoy M (2010) Epidemiological, clinical and microbiological profile of infective endocarditis in a tertiary hospital in the South-East Anatolia Region. Turk Kardiyol Dern Ars 38: 107-111. PubMed: 20473012.
  153. 153. Svanbom M, Strandell T (1978) Bacterial endocarditis. I. A prospective study of etiology, underlying factors and foci of infection. Scand J Infect Dis 10: 193-202. PubMed: 715383.
  154. 154. Sy RW, Chawantanpipat C, Richmond DR, Kritharides L (2011) Development and validation of a time-dependent risk model for predicting mortality in infective endocarditis. Eur Heart J 32: 2016-2026. doi: PubMed: 19329801.
  155. 155. Tariq M, Alam M, Munir G, Khan MA, Smego RA Jr. (2004) Infective endocarditis: a five-year experience at a tertiary care hospital in Pakistan. Int J Infect Dis 8: 163-170. doi: PubMed: 15109591.
  156. 156. Terpenning MS, Buggy BP, Kauffman CA (1987) Infective endocarditis: clinical features in young and elderly patients. Am J Med 83: 626-634. doi: PubMed: 3674051.
  157. 157. Thalme A, Westling K, Julander I (2007) In-hospital and long-term mortality in infective endocarditis in injecting drug users compared to non-drug users: a retrospective study of 192 episodes. Scand J Infect Dis 39: 197-204. doi: PubMed: 17366047.
  158. 158. Thornton JB, Alves JC (1981) Bacterial endocarditis. A retrospective study of cases admitted to the University of Alabama Hospitals from 1969 to 1979. Oral Surg Oral Med Oral Pathol 52: 379-383. doi: PubMed: 6946359.
  159. 159. Tornos P, Iung B, Permanyer-Miralda G, Baron G, Delahaye F et al. (2005) Infective endocarditis in Europe: lessons from the Euro heart survey. Heart 91: 571-575. doi: PubMed: 15831635.
  160. 160. Tran CT, Kjeldsen K (2006) Endocarditis at a tertiary hospital: reduced acute mortality but poor long term prognosis. Scand J Infect Dis 38: 664-670. doi: PubMed: 16857612.
  161. 161. Tuğcu A, Yildirimtürk O, Baytaroğlu C, Kurtoğlu H, Köse O et al. (2009) Clinical spectrum, presentation, and risk factors for mortality in infective endocarditis: a review of 68 cases at a tertiary care center in Turkey. Turk Kardiyol Dern Ars 37: 9-18. PubMed: 19225248.
  162. 162. Venezio FR, Westenfelder GO, Cook FV, Emmerman J, Phair JP (1982) Infective endocarditis in a community hospital. Arch Intern Med 142: 789-792. doi: PubMed: 7073419.
  163. 163. Verheul HA, van den Brink RB, van Vreeland T, Moulijn AC, Düren DR et al. (1993) Effects of changes in management of active infective endocarditis on outcome in a 25-year period. Am J Cardiol 72: 682-687. doi: PubMed: 8249845.
  164. 164. Vlessis AA, Hovaguimian H, Jaggers J, Ahmad A, Starr A (1996) Infective endocarditis: ten-year review of medical and surgical therapy. Ann Thorac Surg 61: 1217-1222. doi: PubMed: 8607686.
  165. 165. Von Reyn CF, Levy BS, Arbeit RD, Friedland G, Crumpacker CS (1981) Infective endocarditis: an analysis based on strict case definitions. Ann Intern Med 94: 505-518. doi: PubMed: 7011141.
  166. 166. Wang HL, Sheng RY (2004) A clinical analysis of 70 cases of infective endocarditis. Zhonghua Nei Ke Za Zhi 43: 33-36. PubMed: 14990019.
  167. 167. Watanakunakorn C, Burkert T (1993) Infective endocarditis at a large community teaching hospital, 1980-1990. A review of 210 episodes. Medicine (Baltimore) 72: 90-102.
  168. 168. Wells AU, Fowler CC, Ellis-Pegler RB, Luke R, Hannan S, et al. (1990) Endocarditis in the 80s in a general hospital in Auckland, New Zealand. Q J Med 76: 753-762.
  169. 169. Welsby PD (1977) Infective endocarditis -- a retrospective study. Practitioner 218: 382-387. PubMed: 846928.
  170. 170. Weng MC, Chang FY, Young TG, Ding YA (1996) Analysis of 109 cases of infective endocarditis in a tertiary care hospital. Zhonghua Yi Xue Za Zhi (Taipei) 58: 18-23.
  171. 171. Werner GS, Schulz R, Fuchs JB, Andreas S, Prange H et al. (1996) Infective endocarditis in the elderly in the era of transesophageal echocardiography: clinical features and prognosis compared with younger patients. Am J Med 100: 90-97. doi: PubMed: 8579094.
  172. 172. Witchitz S, Reidiboym M, Bouvet E, Wolff M, Vachon F (1992) Outcome of prognostic factors of infectious endocarditis over a 16 year period. Apropos of 471 cases. Arch Mal Coeur Vaiss 85: 959-965. PubMed: 1449342.
  173. 173. Wong CW, Porter G, Tisch J, Young C (2009) Outcome and prognostic factors on 57 cases of infective endocarditis in a single centre. N Z Med J 122: 54-62. PubMed: 19859092.
  174. 174. Zamorano J, de Isla LP, Malangatana G, Almería C, Rodrigo JL et al. (2005) Infective endocarditis: mid-term prognosis in patients with good in-hospital outcome. J Heart Valve Dis 14: 303-309. PubMed: 15974522.
  175. 175. Benes J, Baloun R, Dzupová O (2011) Endocarditis 2007: Results of a multicentric study on occurrence and characteristics of infective endocarditis. Vnitr Lek 57: 147-154. PubMed: 21416854.
  176. 176. Benn M, Hagelskjaer LH, Tvede M (1997) Infective endocarditis, 1984 through 1993: a clinical and microbiological survey. J Intern Med 242: 15-22. doi: PubMed: 9260562.
  177. 177. Correa de Sa DD, Tleyjeh IM, Anavekar NS, Schultz JC, Thomas JM et al. (2010) Epidemiological trends of infective endocarditis: a population-based study in Olmsted County, Minnesota. Mayo Clin Proc 85: 422-426. doi: PubMed: 20435834.
  178. 178. Delahaye F, Goulet V, Lacassin F, Ecochard R, Selton-Suty C et al. (1995) Characteristics of infective endocarditis in France in 1991. A 1-year survey. Eur Heart J 16: 394-401. PubMed: 7789383.
  179. 179. Goulet V, Etienne J, Fleurette J, Netter R (1986) Infectious endocarditis in France. Epidemiological characteristics. Presse Med 15: 1855-1858. PubMed: 2947179.
  180. 180. Griffin MR, Wilson WR, Edwards WD, O'Fallon WM, Kurland LT (1985) Infective endocarditis. Olmsted County, Minnesota, 1950 through 1981. JAMA 254: 1199-1202. doi: PubMed: 4021062.
  181. 181. Hoen B, Alla F, Selton-Suty C, Béguinot I, Bouvet A et al. (2002) Changing profile of infective endocarditis: results of a 1-year survey in France. JAMA 288: 75-81. doi: PubMed: 12090865.
  182. 182. Hogevik H, Olaison L, Andersson R, Lindberg J, Alestig K (1995) Epidemiologic aspects of infective endocarditis in an urban population. A 5-year prospective study. Medicine (Baltimore) 74: 324-339. doi:
  183. 183. King JW, Nguyen VQ, Conrad SA (1988) Results of a prospective statewide reporting system for infective endocarditis. Am J Med Sci 295: 517-527. doi: PubMed: 3133947.
  184. 184. Nakatani S, Mitsutake K, Hozumi T, Yoshikawa J, Akiyama M et al. (2003) Current characteristics of infective endocarditis in Japan: an analysis of 848 cases in 2000 and 2001. Circ J 67: 901-905. doi: PubMed: 14578594.
  185. 185. Schnurr LP, Ball AP, Geddes AM, Gray J, McGhie D (1977) Bacterial endocarditis in England in the 1970's: a review of 70 patients. Q J Med 46: 499-512.
  186. 186. Scudeller L, Badano L, Crapis M, Pagotto A, Viale P (2009) Population-based surveillance of infectious endocarditis in an Italian region. Arch Intern Med 169: 1720-1723. PubMed: 19822831.
  187. 187. Smith RH, Radford DJ, Clark RA, Julian DG (1976) Infective endocarditis: a survey of cases in the South-East region of Scotland, 1969-72. Thorax 31: 373-379. doi: PubMed: 968793.
  188. 188. van der Meer JT, Thompson J, Valkenburg HA, Michel MF (1992) Epidemiology of bacterial endocarditis in The Netherlands. I. Patient characteristics. Arch Intern Med 152: 1863-1868. doi: PubMed: 1520052.
  189. 189. Whitby M, Fenech A (1985) Infective endocarditis in adults in Glasgow, 1976-81. Int J Cardiol 7: 391-403. doi: PubMed: 3886562.