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Keywords:

  • Enteroccoccus faecalis ;
  • healthcare-associated infection;
  • infective endocarditis;
  • prognosis;
  • vancomycin resistance

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Transparency Declaration
  9. References
  10. Supporting Information

Enterococci are reportedly the third most common group of endocarditis-causing pathogens but data on enterococcal infective endocarditis (IE) are limited. The aim of this study was to analyse the characteristics and prognostic factors of enterococcal IE within the International Collaboration on Endocarditis. In this multicentre, prospective observational cohort study of 4974 adults with definite IE recorded from June 2000 to September 2006, 500 patients had enterococcal IE. Their characteristics were described and compared with those of oral and group D streptococcal IE. Prognostic factors for enterococcal IE were analysed using multivariable Cox regression models. The patients' mean age was 65 years and 361/500 were male. Twenty-three per cent (117/500) of cases were healthcare related. Enterococcal IE were more frequent than oral and group D streptococcal IE in North America. The 1-year mortality rate was 28.9% (144/500). E. faecalis accounted for 90% (453/500) of enterococcal IE. Resistance to vancomycin was observed in 12 strains, eight of which were observed in North America, where they accounted for 10% (8/79) of enterococcal strains, and was more frequent in Efaecium than in Efaecalis (3/16 vs. 7/364 , p 0.01). Variables significantly associated with 1-year mortality were heart failure (HR 2.4, 95% CI 1.7—3.5, p <0.0001), stroke (HR 1.9, 95% CI 1.3—2.8, p 0.001) and age (HR 1.02 per 1-year increment, 95% CI 1.01—1.04, p 0.002). Surgery was not associated with better outcome. Enterococci are an important cause of IE, with a high mortality rate. Healthcare association and vancomycin resistance are common in particular in North America.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Transparency Declaration
  9. References
  10. Supporting Information

Enterococci are reportedly the third most common group of endocarditis-causing pathogens after streptococci and staphylococci. A few, relatively small, case series of enterococcal infective endocarditis (IE) have been published [1-9]. Based on these studies, the most distinctive features of enterococcal IE are that they more frequently affect elderly and prosthetic valve patients [3, 5, 8], and are more often nosocomially acquired than other forms of IE [2, 7]. Nosocomial acquisition appears to worsen outcome. The mortality rate is intermediate to that of streptococcal and staphylococcal IE [1, 2, 4, 8]. Patients with prosthetic valve enterococcal IE are more likely to develop intracardiac abscesses and less likely to have detectable vegetations on echocardiography than patients with native valve enterococcal IE [3]. In contrast, native and prosthetic valve enterococcal IE do not appear to differ in rate of complications, need for surgery or mortality [1].

To date, all but two [4, 6] of these case series were collected retrospectively and some are more than 20 years old [9]. The aim of this study was to analyse the current characteristics and prognostic factors of enterococcal IE within the International Collaboration on Endocarditis – Prospective Cohort Study (ICE-PCS), which forms the largest series of IE ever collected prospectively.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Transparency Declaration
  9. References
  10. Supporting Information

International Collaboration on Endocarditis – Prospective Cohort Study

Data from the ICE-PCS were used for this study. The background and inclusion criteria of this prospective, multicentre, international registry of IE have been reported previously [10, 11]. Between June 2000 and September 2006, 4794 patients from 64 centres in 28 countries were enrolled. The ICE-PCS database is maintained at the Duke Clinical Research Institute, the coordinating centre for ICE studies. Informed consent (oral/written) was obtained from all patients according to local institutional review boards or ethics committee guidelines at all sites.

Patient selection and data collection

Patients were identified prospectively using site-specific procedures to ensure consecutive enrollment. Patients were enrolled in the ICE-PCS if they met criteria for possible or definite IE based on the modified Duke criteria [12]. Only patients with definite IE were included in the current study. To preserve the assumption of independence of observations, only the first episode of IE recorded for an individual patient was used in the analysis.

The method of data collection for the ICE-PCS has been previously reported [11]. Briefly, all sites used a standard case report form to collect data. It included 275 variables and was developed by the ICE according to standard definitions. Data were collected during the index hospitalization and then entered at the coordinating centre or by site investigators using an Internet-based data entry system. Microbial species identifications were performed locally in each medical centre according to its own procedures. All sites obtained information on 1-year survival through the civil registry office, medical records and/or patient contact when necessary.

Definitions and case groups

Definitions of the variables included in the ICE-PCS case report form have been previously reported [11].

Community-acquired IE was defined as IE diagnosed at the admission time (or within the first 48 h) in a patient who did not fulfill the criteria for healthcare-associated infection. Healthcare-associated IE was defined as nosocomial IE or non-nosocomial healthcare-associated IE. Nosocomial IE was defined as IE that developed in a patient who was hospitalized for more than 48 h before the onset of signs or symptoms consistent with IE. Non-nosocomial healthcare-associated IE was defined as IE diagnosed within 48 h of admission in an outpatient with extensive healthcare contact, as reflected by any of the following criteria: (i) receipt of intravenous therapy, wound care or specialized nursing care at home within the 30 days before the onset of IE; (ii) attendance at a hospital or haemodialysis clinic or receipt of intravenous chemotherapy within the 30 days before the onset of IE; (iii) hospitalization in an acute care hospital for 2 or more days in the 90 days before the onset of IE; or (iv) residence in a nursing home or long-term care facility.

In an effort to group centres with geographical and sociodemographic similarities, five meta-regions were defined as follows: North America, South America, Northern Europe, Southern Europe/Middle East/Africa and Australia/New Zealand/Asia (see supporting data).

The group of enterococcal IE included all cases of IE due to E. faecalis, E. faecium, E. durans, E. avium, E. casseliflavus or E. gallinarum, as well as enterococci that could not be further identified to the species level. For comparative analyses, we formed two additional groups of IE, oral streptococci IE and group D streptococci IE. Table 1 shows the list of organisms that are included in these two groups. We did this because enterococci, oral and group D streptococci all belong to the Streptococcaceae family.

Table 1. List of pathogens included in the three groups of pathogens used for comparative analysis
Enterococci N Oral streptococci N Group D streptococci N
  1. a

    S. bovis’ refers to the results of species identification according to the former, outdated classification of group D streptococci.

  2. b

    Not identified to species level.

E. faecalis 453 S. mitis 79 S. bovis a 270
E. faecium 19 S. mutans 64 S. gallolyticus 17
E. durans 6 S. oralis 42 S. equinus 2
E. casseliflavus 2 S. sanguis 31 S. pasteurianus 1
E. gallinarum 1 S. salivarius 23Group D NISb3
Enterococci NISb19 S. gordonii 12
S. anginosus 17
S. constellatus 5
S. intermedius 5
S. milleri group NISb4
S. acidominimus 7
S. parasanguis 1
S. viridans NISb533
TOTAL500 823 293

Statistical analysis

Data are presented as mean (SD) for continuous variables and as percentages for categorical variables. Simple comparisons were made using Kruskal–Wallis, chi-squared or Fisher exact tests as appropriate.

Multivariable Cox regression analysis was used to identify factors associated with in-hospital mortality. The endpoint was the status (dead vs. alive) 1 year after discharge from hospital. The following variables were evaluated for their potential impact on prognosis: age, sex, ICE meta-regions, Charlson index, diabetes mellitus, cancer, haemodialysis, valve prosthesis before IE, nosocomial acquisition, heart failure (defined by NYHA class 3 or 4), stroke, development of at least one paravalvular complication, and cardiac surgery. The latter variable was assigned a time-dependent format, as recommended for assessing the impact of cardiac surgery on outcome [13]. For multivariable analysis, variables entered into the model were those with a p-value ≤0.05 in bivariable analysis. A stepwise variable selection was then performed, with an enter p-value of 0.05 and a remove p-value of 0.05. Two age- and sex-adjusted models were built up: one within the group of enterococcal IE to identify prognostic factors associated with this condition and one across the three pooled groups to assess the impact of enterococci vs. oral streptococci and vs. group D streptococci on IE prognosis.

For all tests, statistical significance was determined at the 0.05 level. All statistical analyses were performed using SAS software (version 9.2, SAS Institute, Cary, NC, USA).

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Transparency Declaration
  9. References
  10. Supporting Information

A total of 1616 patients with definite streptococcal or enterococcal IE were identified according to the selection criteria (Fig. 1). There were 500 cases of enterococcal IE (30.9%), 823 cases of oral streptococcal IE (51.0%) and 293 cases of group D streptococcal IE (18.1%). The distribution of species is shown in Table 1.

image

Figure 1. Patients' selection flow-chart.

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Of the 500 patients with enterococcal IE, 361 (72.6%) were male. The patients' mean age was 65.5 (15.3) years. The proportion of healthcare-associated IE was 117/500 (23.4%) (65/500 nosocomial and 52/500 non-nosocomial). Patients undergoing chronic haemodialysis accounted for 41/500 (8.4%). IE developed on native valves in 324/488 (66.4%) patients and on prosthetic valves in 142/488 (29.1%) patients. In the remaining 34 patients, the location of IE was either extravalvular or unknown. In terms of clinical manifestations, the only significant difference between E. faecalis and E. faecium IE consisted of a higher incidence of stroke in E. faecalis IE (16% vs. 0%, p 0.05). Two hundred and nine of the 497 patients (42.1%) underwent valve surgery during the initial hospital stay. Patients with prosthetic valve IE were less often operated on than patients with native valve IE (49/142 vs. 151/321, p 0.012). Non-operated patients were older than operated ones (68.5 vs. 62 years, p <0.001).

The 1-year mortality rate was 144/498 (28.9%), and higher in prosthetic valve IE than in native valve IE (55/142 vs. 80/322, p 0.002). The 1-year mortality rate did not differ between operated and non-operated patients in the overall enterococcal IE (56/219 vs. 88/278, p 0.14). Nor did it differ in native (32/144 vs. 48/177, p 0.3) or prosthetic (17/46 vs. 38/96, p 0.76) valve IE subgroups.

Overall, resistance to ampicillin and vancomycin was observed in 18 and 12 enterococcal strains, respectively. Seven of the 11 vancomycin-resistant strains were isolated from nosocomially-acquired IE, whereas this was the case for only 49/386 (13%) vancomycin-susceptible strains (p 0.004) (the place of acquisition was unknown or missing in one case of vancomycin-resistant IE and in 17 cases of vancomycin-susceptible IE). Eight of the 12 vancomycin-resistant strains (66.7%) were observed in North America, where they accounted for 10% of enterococcal strains. In contrast, no vancomycin resistance was observed in South Africa and Australia/New Zealand and the percentages of vancomycin resistance were only 1.0% (1/105 strains) in Northern Europe and 2.7% (3/111 strains) in Southern Europe/Middle East/Africa. The overall rate of high-level resistance to aminoglycoside was 111/290 (38%). It was lower in North America (12/54, 22%) than in the other four meta-regions (p 0.0002).

In addition, resistance to ampicillin and resistance to vancomycin were observed more often in E. faecium than in E. faecalis strains (9/16 vs. 8/404, p <0.0001 and 3/16 vs. 7/364, p 0.01, respectively). Resistance to aminoglycoside was not different between the two species. The 1-year mortality rate was higher in vancomycin-resistant than in vancomycin-susceptible enterococcal IE (7/12 vs. 110/384, p 0.03). Patients treated with an aminoglycoside-containing regimen presented a lower 1-year mortality rate than patients treated without aminoglycoside (57/218 vs. 29/68, p 0.01).

The comparative characteristics of enterococcal, oral streptococcal and group D streptococcal IE are summarized in Fig. 2 and Table 2. Enterococcal IE were more common than oral and group D streptococcal IE in North America, where they accounted for 50.3% of the cases when pooling the three groups. In all four other meta-regions, the ranking was more conventional, with oral streptococci, enterococci and group D streptococci occurring in descending order (Fig. 2). Comparison of the three organism groups demonstrated the following characteristics of enterococcal IE. Enterococcal IE more often developed in relation to healthcare intervention and in elderly patients with co-morbid conditions, as exhibited by a higher proportion of patients with diabetes or receiving haemodialysis and by a higher Charlson index. Patients with enterococcal IE more often had a prior history of IE, a prosthetic valve or an implanted intracardiac device. The course of the disease did not differ significantly in terms of frequency and type of complications, although the time between first symptoms and admission was significantly shorter in enterococcal IE, which may reflect a more aggressive course of the disease and/or a more rapid diagnosis of healthcare-associated cases. The 1-year mortality rate was significantly higher for enterococcal than for streptococcal IE (Table 2).

Table 2. Main characteristics of enterococcal IE compared with those of oral and group D streptococcal IE
 Enterococci n = 500 30.9%Oral streptococci n = 823 51.0%Group D streptococci n = 293 18.1%p value
  1. IE, infective endocarditis.

  2. Percentages are based on the missing data.

Age (years), mean [SD]65.5 (15.3)54.6 (18.4)65.2 (12.4)<0.0001
Male sex, N (%)361 (72.6)584 (71.0)218 (74.7)0.46
History of IE, N (%) 62 (12.5) 86 (10.5) 21 (7.2)0.07
Admission delay > 1 month, N (%)172 (36.8)350 (44.9)142 (51.4)<0.0001
Haemodialysis, N (%) 41 (8.4) 11 (1.4) 6 (2.1)<0.0001
Diabetes, N (%)110 (22.4) 90 (11.1) 56 (19.3)<0.0001
Cancer, N (%) 55 (11.2) 67 (8.3) 34 (11.7)0.11
Charlson index, mean [SD] 1.7 (1.8) 1.0 (1.5) 1.3 (1.5)<0.0001
Place of acquisition, N (%)<0.0001
Community352 (70.4)758 (92.1)280 (95.6)
Healthcare, nosocomial 65 (13.0) 12 (1.5) 3 (1.0)
Healthcare, non-nosocomial 52 (10.4) 25 (3.0) 4 (1.4)
Multiple, unknown, missing 31 (6.2) 28 (3.4) 6 (2.0)
Intracardiac device, N (%) 61 (12.4) 31 (3.8) 21 (7.2)<0.0001
Type of IE, N (%)<0.0001
Native valve324 (66.4)641 (80.9)216 (75.8)
Prosthetic valve142 (29.1)130 (16.4) 62 (21.8)
Other 22 (4.5) 21 (2.7) 7 (2.5)
Location of vegetation, N (%)0.18
Left-sided only380 (80.3)643 (83.0)241 (87.6)
Right-sided only 26 (5.5) 27 (3.5) 6 (2.2)
Left + right11 (2.3) 14 (1.8) 4 (1.5)
Elsewhere 16 (3.4) 18 (2.3) 4 (1.5)
No vegetation 40 (8.5) 73 (9.4) 20 (7.3)
Missing information 27 (5.4) 48 (5.8) 18 (6.1)
Stroke, N (%) 78 (16.0)118 (14.7) 38 (13.3)0.59
Embolic event, N (%) 94 (19.3)147 (18.3) 70 (24.4)0.08
Heart failure, N (%) 94 (18.8)139 (16.9) 56 (19.1)0.90
Intracardiac abscess, N (%) 57 (11.8)110 (13.6) 33 (11.5)0.51
Paravalvular complications in prosthetic valve IE, N (%) 53 (10.8) 41 (5.1) 15 (5.2)0.0002
Valve surgery within 60 days, N (%)209 (42.1)380 (46.5)137 (47.2)0.22
One-year mortality, N (%)144 (28.9)120 (14.6) 52 (17.8)<0.0001
image

Figure 2. Percentages of enterococci, oral streptococci and group D streptococci as the causative agents of IE among the five ICE meta-regions.

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The variables that were analysed as potential prognostic factors for enterococcal IE are listed in Table 3. After bivariable analysis, six variables were then selected for the age- and sex-adjusted multivariable model. Finally, three variables were identified as significantly and independently associated with 1-year mortality. These were heart failure (HR 2.43 vs. no heart failure, 95% CI 1.71—3.45, p <0.0001), stroke (HR 1.90 time-dependent, 95% CI 1.28—2.82, p 0.001) and age (HR 1.02 per 1-year increment, 95% CI 1.01—1.04, p 0.002). Valve surgery, as a time-dependent variable, had no impact on prognosis. The same analyses were redone on the subgroup of E. faecalis IE and led to essentially the same results (i.e. the same prognostic factors were identified and associated with similar HRs (data not shown)).

Table 3. Results of prognosis analysis by Cox regression analysis within the group of enterococcal IE. The multivariable model is adjusted for age and sex. The endpoint is 1-year mortality
  Bivariable analysis Multivariable analysis
HR 95% CI HR 95% CI
  1. The variables selected as psoguotic factors are shown in bold.

Age, per 1-year increment 1.02 1.01–1.03 1.02 1.01–1.04
Sex, male vs. female0.720.49–1.07
Charlson index, per 1-unit increment 1.29 1.11–1.50
Haemodialysis, yes vs. no1.150.65–2.04
Diabetes, yes vs. no1.370.95–1.98
Cancer, yes vs. no 1.62 1.04–2.53
Nosocomial acquisition, yes vs. no0.860.53–1.42
Stroke (time-dependent) 2.00 1.36–2.94 1.90 1.28–2.82
Heart failure, yes vs. no 2.47 1.75–3.50 2.43 1.71–3.45
Paravalvular complications 1.48 1.06–2.06
Surgery (time-dependent)1.040.74–1.46

In order to assess the role of enterococci as a potential prognostic factor, we built a multivariable model based on the pooled 1616 cases of IE. This model identified the same prognostic factors as in the previous step and three additional factors: diabetes, presence of a prosthetic valve before IE, and causative microorganism. The model thus demonstrated a significantly lower risk of death for oral streptococcal IE (HR 0.62, 95% CI 0.45—0.87) and group D streptococcal IE (HR 0.65, 95% CI 0.50–0.85), as compared with enterococcal IE (Table 4).

Table 4. Identification of prognostic factors by Cox regression analysis in the pooled three groups of IE. The multivariable model is adjusted for age and sex. The endpoint is 1-year mortality
  Bivariable analysis Multivariable analysis
HR 95% CI HR 95% CI
  1. The variables selected as psoguotic factors are shown in bold.

Age, per 1-year increment 1.03 1.02–1.04 1.02 1.01–1.03
Sex, male vs. female0.950.74–1.22
Charlson index, per 1-unit increment 1.42 1.27–1.57
Haemodialysis, yes vs. no 1.91 1.20–3.03
Diabetes, yes vs. no 1.63 1.25–2.12 1.43 1.09–1.88
Cancer, yes vs. no 1.94 1.44–2.62
Valve prosthesis before IE, yes vs. no 1.82 1.44–2.29
Nosocomial acquisition, yes vs. no1.521.00–2.33
Stroke (time-dependent) 2.31 1.78–2.99 2.23 1.71–2.91
Heart failure, yes vs. no 2.88 2.29–3.63 2.77 2.15–3.57
Paravalvular complications 1.71 1.37–2.14
Surgery (time-dependent)1.070.85–1.35
Causative microorganism
Enterococci11
Oral streptococci 0.46 0.36–0.58 0.62 0.45–0.87
Group D streptococci 0.54 0.39–0.74 0.65 0.50–0.85

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Transparency Declaration
  9. References
  10. Supporting Information

This study confirms that E. faecalis accounts for about 90% of enterococcal IE, as previously reported [3]. Overall, enterococcal IE forms the third most important group of IE after streptococcal and staphylococcal IE. Interestingly, in this study, enterococcal IE was more frequent than both oral and group D streptococcal IE in North America, which may be related to the higher proportion of healthcare-associated IE in this part of the world [14], a hypothesis supported by the significantly higher rate of resistance to ampicillin and vancomycin for enterococci in North America as compared with the rest of the world. The present study also confirms that enterococcal IE is less often community acquired or involving native valves than previously reported. We actually found that among enterococcal IE, almost 25% were healthcare-associated IE, especially nosocomial, and 30% were prosthetic valve IE. In addition, enterococcal IE mainly affects elderly and debilitated patients. Interestingly, this newer profile was not associated with a higher rate of complications compared with oral or group D streptococcal IE. The in-hospital mortality rate of enterococcal IE, although significantly higher than in streptococcal IE despite a shorter delay to diagnosis, remained within the range of 11–18% observed in previous series [1, 2, 4]. In terms of prognosis, we failed to identify any factors specific to enterococcal IE, whose prognosis was mainly affected by age, occurrence of stroke and heart failure. However, we found that Enterococcus as the cause of IE was an adverse independent prognostic factor for mortality within the group of IE due to Streptococcaceae. In addition, after integration into the model of the 1471 cases of Staphylococcus aureus IE contained in the ICE-PCS database (data not shown), we found that Staphylococcus aureus as the cause of IE was associated with a higher risk of death (HR 1.6, 95% CI 1.3—2), which confirmed the lower risk of death associated with oral and group D streptococci.

The major strength of this study is that it assembled the largest series of prospectively collected cases of enterococcal IE ever published. Cases were collected recently and rapidly (the first 6 years of the 21st century), providing an accurate view of the current profile of this disease.

A limitation of our study is the fact that case collection was tertiary care centre-based and not population-based. This may have introduced a referral bias towards a selection of more severe cases than the ‘average’. However, in a large prospective population-based study of IE conducted recently, where enterococcal IE represented 10.5% (n = 52) of the 497 cases of IE collected, enterococcal IE was the third most frequent group of IE, occurred more frequently in patients with prosthetic valves, and was more prone to be nosocomially acquired than oral or group D streptococcal IE [15]. Therefore we can reasonably assume that this ICE-PCS series is representative of enterococcal IE in clinical practice. Another limitation is the fact that the impact of the antibiotic regimens on prognosis could not be analysed because the ICE-PCS database contains few details about the treatment: overall planned duration and predominant antibiotics used. Furthermore, this information was missing in about half of the study population, which could bias results. Finally, bacteriological identification techniques were not standardized because each centre used its own procedures. This explains the high rate of ‘viridans’ streptococci.

Enterococcal infection is an increasingly important cause of IE with a high mortality rate. Those affected include the elderly and patients with prosthetic valves or intracardiac devices. Healthcare association is common, in particular in North America, where emerging resistance to vancomycin is a matter of concern.

Acknowledgments

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Transparency Declaration
  9. References
  10. Supporting Information

ICE investigators: Argentina: Liliana Clara, MD, Marisa Sanchez, MD (Hospital Italiano), Francisco Nacinovich, MD, Pablo Fernandez Oses, MD, Ricardo Ronderos, MD, Adriana Sucari, MD, Jorge Thierer, MD (Instituto Cardiovascular), José Casabé, MD, PhD, Claudia Cortes, MD, (Hospital Universitario de la Fundaciòn Favaloro), Javier Altclas, MD, Sanatorio, Silvia Kogan, MD (Sanatorio de la Trinidad Mitre). Australia: Denis Spelman, MD (Alfred Hospital). Eugene Athan, MD, Owen Harris, MBBS, (Barwon Health), Karina Kennedy, MBBS, Ren Tan, MBBS (Canberra Hospital), David Gordon, MBBS, PhD, Lito Papanicolas, MBBS (Flinders Medical Centre), Damon Eisen, MBBS, MD, Leeanne Grigg, MBBS, Alan Street, MBBS (Royal Melbourne Hospital), Tony Korman, MD, Despina Kotsanas, BSc (Hons) (Southern Health), Robyn Dever, MD, Phillip Jones, MD, Pam Konecny, MD, Richard Lawrence, MD, David Rees, MD, Suzanne Ryan, MHSc (St George Hospital), Michael P. Feneley, MD, John Harkness, MD, Phillip Jones, MD, Suzanne Ryan, MHSc (St Vincent's). Austria: Phillip Jones, MD, Suzanne Ryan, MHSc (Sutherland), Phillip Jones, MD, Jeffrey Post, MD, Porl Reinbott, Suzanne Ryan, MHSc (The University of New South Wales), Rainer Gattringer, MD, Franz Wiesbauer, MD (Vienna General Hospital). Brazil: Adriana Ribas Andrade, Ana Cláudia Passos de Brito, Armenio Costa Guimarães, MD (Ana Neri Hospital), Max Grinberg, MD, PhD, Alfredo José Mansur MD, PhD, Rinaldo Focaccia Siciliano, MD, Tania Mara Varejao Strabelli, MD, Marcelo Luiz Campos Vieira, MD (Heart Institute (Incor), University of Sao Paulo Medical School), Regina Aparecida de Medeiros Tranchesi, MD, Marcelo Goulart Paiva, MD (Hospital 9 de Julho), Claudio Querido Fortes, MD (Hospital Universitario Clementino Fraga Filho/UFRJ), Auristela de Oliveira Ramos, MD (Instituto Dante Pazzanese de Cardiologia), Giovanna Ferraiuoli, MD, Wilma Golebiovski, MD, Cristiane Lamas, MD, PhD, Marisa Santos, MD, PhD, Clara Weksler, MD (Instituto Nacional de Cardiologi). Canada: James A. Karlowsky, MD, Yoav Keynan, MD, Andrew M. Morris, MD, Ethan Rubinstein, MD, LL.B (University of Manitoba). Chile: Sandra Braun Jones, MD, Patricia Garcia, MD (Hospital Clínico Pont. Universidad Católica de Chile). M Cereceda, MD, Alberto Fica, Rodrigo Montagna Mella, MD (Hospital Clinico Universidad de Chile). Croatia: Bruno Barsic, MD, PhD, Suzana Bukovski, MD, PhD Vladimir Krajinovic, MD, Ana Pangercic, MD, Igor Rudez, MD, Josip Vincelj, MD, PhD (University Hospital for Infectious Diseases). Czech Republic: Tomas Freiberger, MD, PhD, Jiri Pol, MD, Barbora Zaloudikova, MSc (Centre for Cardiovascular Surgery and Transplantation). Egypt: Zainab Ashour, MD, Amani El Kholy, MD, Marwa Mishaal, MD, Hussien Rizk, MD (Cairo University Medical School). France: Neijla Aissa, MD, Corentine Alauzet, MD, Francois Alla, MD, PhD, CHU, Catherine Campagnac, RN, Thanh Doco-Lecompte, MD, Christine Selton-Suty, MD (CHU Nancy-Brabois), Jean-Paul Casalta, MD, Pierre-Edouard Fournier, MD, Gilbert Habib, MD, Didier Raoult, MD, PhD, Franck Thuny, MD (Faculté de Médecine de Marseille), Francois Delahaye, MD, PhD, Armelle Delahaye, Francois Vandenesch, MD (Hospital Louis Pradel), Erwan Donal, MD, Pierre Yves Donnio, PhD, Christian Michelet, MD, PhD, Matthieu Revest, MD, Pierre Tattevin, MD, PhD, Jérémie Violette, MD (Pontchaillou University), Florent Chevalier, MD, Antoine Jeu, MD, Dan MD Rusinaru, MD, Claire Sorel, MD, Christophe Tribouilloy, MD, PhD (South Hospital Amiens), Yvette Bernard, MD, Catherine Chirouze, MD, Bruno Hoen, MD, PhD, Joel Leroy, MD, Patrick Plesiat, MD (University Medical Center of Besançon). Germany: Christoph Naber, MD, PhD, Carl Neuerburg (Universitaetskliniken Bergmannsheil Bochum), Bahram Mazaheri, PhD, Christoph Naber, MD, PhD, Carl Neuerburg (University Essen). Greece: Sofia Athanasia, MD, Efthymia Giannitsioti, MD (Attikon University General Hospital), Elena Mylona MD, Olga Paniara MD, PhD, Konstantinos Papanicolaou, MD, John Pyros MD, Athanasios Skoutelis MD, PhD (Evangelismos General Hospital of Athens). India: Gautam Sharma, MD (All India Institute of Medical Sciences), Johnson Francis, MD, DM, Lathi Nair, MD, DM, Vinod Thomas, MD, DM, Krishnan Venugopal, MD, DM (Medical College Calicut). Ireland: Margaret Hannan, MB, BCh BAO, MSc, John Hurley, MB, BCh (Mater Hospitals). Israel: Dan Gilon, MD, Sarah Israel, MD, Maya Korem, MD, Jacob Strahilevitz, MD (Hadassah-Hebrew University), Ethan Rubinstein, MD, LL.B, Jacob Strahilevitz, MD (Tel Aviv University School of Medicine). Italy: Roberta Casillo, MD, PhD, Susanna Cuccurullo, MSc, Giovanni Dialetto, MD, Emanuele Durante-Mangoni, MD, PhD, Mattucci Irene, MD, Enrico Ragone, MD, PhD, Marie Françoise Tripodi, MD, Riccardo Utili, MD, PhD (II Università di Napoli), Enrico Cecchi, MD, Francesco De Rosa, MD, Davide Forno, MD, Massimo Imazio, MD, Rita Trinchero, MD (Maria Vittoria Hospital), Alessandro Tebini, MD, Paolo Grossi, MD, PhD, Mariangela Lattanzio, MD, Antonio Toniolo, MD (Ospedale di Circolo Varese), Antonio Goglio, MD, Annibale Raglio, MD, DTM&H, Veronica Ravasio, MD, Marco Rizzi, MD, Fredy Suter, MD (Ospedali Riuniti di Bergamo), Giampiero Carosi, MD, Silvia Magri, MD, Liana Signorini, MD (Spedali Civili – Università di Brescia). Lebanon: Tania Baban, MD, Zeina Kanafani, MD, MS, Souha S.Kanj, MD, Mohamad Yasmine, MD (American University of Beirut Medical Center). Malaysia: Imran Abidin, MD (University of Malaya Medical Center), Syahidah Syed Tamin, MD (National Heart Institute). Mexico: Eduardo Rivera Martínez, MD, Gabriel Israel Soto Nieto, MD (Instituto Nacional de Cardiología Ignacio Chávez). Netherlands: Jan T.M. van der Meer, MD, PhD (University of Amsterdam). New Zealand: Stephen Chambers, MD, MSc (University of Otago), David Holland, MB, ChB, PhD (Middlemore Hospital), Arthur Morris, MD (Diagnostic Medlab), Nigel Raymond, MB, ChB (Wellington Hospital), Kerry Read, MB, ChB (North Shore Hospital), David R. Murdoch, MD, MSc, DTM&H (University of Otago). Romania: Stefan Dragulescu, MD, PhD, Adina Ionac, MD, PhD, Cristian Mornos, MD (Victor Babes University of Medicine and Pharmacy). Russia: O.M. Butkevich, PhD (Learning-Scientific Centre of Medical Centre of Russian Presidential Affairs Government Medical Centre of Russian), Natalia Chipigina, PhD, Ozerecky Kirill, MD, Kulichenko Vadim, Tatiana Vinogradova, MD, PhD (Russian Medical State University). Saudi Arabia: Jameela Edathodu, MBBS, Magid Halim, MBBS (King Faisal Specialist Hospital & Research Center). Singapore: Luh-Nah Lum, BSN, Ru-San Tan, MBBS (National Heart Centre). Slovenia: Tatjana Lejko-Zupanc, MD, PhD, Mateja Logar, MD, PhD, Manica Mueller-Premru, MD, PhD (Medical Center Ljublijana). South Africa: Patrick Commerford, MD, Anita Commerford, MD, Eduan Deetlefs, MD, Cass Hansa, MD, Mpiko Ntsekhe, MD (University of Cape Town and Groote Schuur Hospital). Spain: Manuel Almela, MD, Yolanda Armero, MD, Manuel Azqueta, MD, Ximena Castañeda, MD, Carlos Cervera, MD, Ana del Rio, MD, PhD, Carlos Falces, MD, Cristina Garcia-de-la-Maria, PhD, Guillermina Fita, MD, Jose M. Gatell, MD, PhD, Francesc Marco, MD, PhD, Carlos A. Mestres, MD, PhD, José M. Miró, MD, PhD, Asuncion Moreno, MD, PhD, Salvador Ninot, MD, Carlos Paré, MD, PhD, Joan Pericas, MD, Jose Ramirez, MD, PhD, Irene Rovira, MD, Marta Sitges, MD (Hospital Clinic – IDIBAPS, University of Barcelona, Barcelona, Spain), Ignasi Anguera, MD, PhD, Bernat Font, MD, Joan Raimon Guma, MD (Hospitál de Sabadell), Javier Bermejo, Emilio Bouza, MD, PhD, Miguel Angel Garcia Fernández, MD, Victor Gonzalez-Ramallo, MD, Mercedes Marín, MD, Patricia Muñoz, MD, PhD, Miguel Pedromingo, MD, Jorge Roda, Marta Rodríguez-Créixems, MD, PhD, Jorge Solis, MD (Hospital General Universitario Gregorio Marañón), Benito Almirante, MD, Nuria Fernandez-Hidalgo, MD, Pilar Tornos, MD (Hospital Universitari Vall d'Hebron), Arístides de Alarcón, Ricardo Parra (Hospital Universitario Virgen del Rocío). Sweden: Eric Alestig, MD, Magnus Johansson, MD, PhD, Lars Olaison, MD, PhD, Ulrika Snygg-Martin, MD (Sahlgrenska Universitetssjukhuset/Östra). Thailand: Orathai Pachirat, MD, Pimchitra Pachirat, MD, Burabha Pussadhamma, MD, Vichai Senthong, MD (Khon Kaen University). United Kingdom: Anna Casey, MBBS, Tom Elliott, PhD, DSc, Peter Lambert, BSc, PhD, DSc, Richard Watkin, MBBS (Queen Elizabeth Hospital), Christina Eyton, John L. Klein, MD (St Thomas' Hospital). United States of America: Suzanne Bradley, MD, Carol Kauffman, MD (Ann Arbor VA Medical Center), Roger Bedimo, MD, MS (Dallas VA Medical Center), Vivian H. Chu, MD, MHS, G. Ralph Corey, MD, Anna Lisa Crowley, MD, MHS, Pamela Douglas, MD, Laura Drew, RN, BSN, Vance G. Fowler, MD, MHS, Thomas Holland, MD, Tahaniyat Lalani, MBBS, MHS, Daniel Mudrick, MD, Zaniab Samad, MD, MHS, Daniel Sexton, MD, Martin Stryjewski, MD, MHS, Andrew Wang, MD, Christopher W. Woods, MD, MPH (Duke University Medical Center), Stamatios Lerakis, MD (Emory University), Robert Cantey, MD, Lisa Steed, PhD, Dannah Wray, MD, MHS (Medical University of South Carolina), Stuart A. Dickerman, MD (New York University Medical Center), Hector Bonilla, MD, Joseph DiPersio, MD, PhD, Sara-Jane Salstrom, RN (Summa Health System), John Baddley, MD, Mukesh Patel, MD (University of Alabama at Birmingham), Gail Peterson, MD, Amy Stancoven, MD (UT-Southwestern Medical Center), Luis Afonso, MD, Theresa Kulman, RN, Donald Levine, MD, Michael Rybak, PharmD, MPH (Wayne State University), Christopher H. Cabell, MD, MHS (Quintiles).

ICE Coordinating Center: Khaula Baloch, MPH, Vivian H. Chu, MD, MHS, G. Ralph Corey, MD, Christy C. Dixon, Vance G. Fowler, Jr, MD, MHS, Tina Harding, RN, BSN, Marian Jones-Richmond, Paul Pappas, MS, Lawrence P. Park, PhD, Thomas Redick, MPH, Judy Stafford, MS.

ICE Publications Committee: Kevin Anstrom, PhD, Eugene Athan, MD, Arnold S. Bayer, MD, Christopher H. Cabell, MD, MHS, Vivian H. Chu, MD, MHS, G. Ralph Corey, MD, Vance G. Fowler, Jr, MD, MHS, Bruno Hoen, MD, PhD, A W Karchmer MD, José M. Miró, MD, PhD, David R. Murdoch, MD, MSc, DTM&H, Daniel J. Sexton MD, Andrew Wang MD.

ICE Steering Committee: Arnold S. Bayer, MD, Christopher H Cabell, MD, MHS, Vivian Chu MD, MHS, G. Ralph Corey MD, David T. Durack, MD, D Phil, Susannah Eykyn, MD, Vance G. Fowler, Jr, MD, MHS, Bruno Hoen MD, PhD, José M. Miró, MD, PhD, Phillipe Moreillon, MD PhD, Lars Olaison, MD, PhD, Didier Raoult, MD, PhD, Ethan Rubinstein MD, LLB, Daniel J, Sexton, MD.

Investigator Grants: American Heart Association 0675027N (VHC), a Red Española de Investigación en Patología Infecciosa (REIPI RD06/0008) and the Fundación Privada Máximo Soriano Jiménez (Barcelona, Spain) (JMM, CGDM). Dr J. M. Miro was a recipient of an INT10/219 Intensification Research Grant (I3SNS & PRICS programs) from the Instituto de Salud Carlos III, Madrid (Spain) and the Departament de Salut de la Generalitat de Catalunya, Barcelona (Spain).

Transparency Declaration

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Transparency Declaration
  9. References
  10. Supporting Information

This work has not been funded. The ICE investigators received grants (American Heart Association 0675027N (VHC), a Red Española de Investigación en Patología Infecciosa” (REIPI RD06/0008) and the Fundación Privada Máximo Soriano Jiménez (Barcelona, Spain) (JMM, CGDM). Dr. JM Miro was a recipient of an INT10/219 Intensification Research Grant (I3SNS & PRICS programs) from the Instituto de Salud Carlos III, Madrid (Spain) and the Departament de Salut de la Generalitat de Catalunya, Barcelona (Spain)). The authors have no relationship (commercial or otherwise) that may constitute a dua or conflict of interest.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Transparency Declaration
  9. References
  10. Supporting Information
  • 1
    Fernandez Guerrero ML, Goyenechea A, Verdejo C, Roblas RF, de Górgolas M. Enterococcal endocarditis on native and prosthetic valves: a review of clinical and prognostic factors with emphasis on hospital-acquired infections as a major determinant of outcome. Medicine (Baltimore) 2007; 86: 363377.
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    Bannay A, Hoen B, Duval X et al. 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 2011; 32: 20032015.
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Supporting Information

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Transparency Declaration
  9. References
  10. Supporting Information
FilenameFormatSizeDescription
clm12166-sup-0001-SupportingData.docxWord document20KTable S1. Distribution of centres by countries and meta-regions in the ICE-PCS.

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