Open Access

Infective endocarditis requiring ICU admission: epidemiology and prognosis

  • Olivier Leroy1Email author,
  • Hugues Georges1,
  • Patrick Devos2,
  • Steve Bitton3,
  • Nathalie De Sa4,
  • Céline Dedrie5,
  • Sébastien Beague6,
  • Pierre Ducq7,
  • Claire Boulle-Geronimi8,
  • Damien Thellier1,
  • Fabienne Saulnier3 and
  • Sebastien Preau3
Annals of Intensive Care20155:45

https://doi.org/10.1186/s13613-015-0091-7

Received: 22 September 2015

Accepted: 17 November 2015

Published: 1 December 2015

Abstract

Background

Very few studies focused on patients with severe infective endocarditis (IE) and multiple complications leading to Intensive Care Unit (ICU) admission. Studied primary outcomes depended on the series and multiple prognostic factors have been identified. Our goal was to determinate characteristics of patients, in-hospital mortality and independent prognostic factors in an overall population of patients admitted to ICU for a left-sided, definite, active and severe IE.

Methods

Retrospective study performed in 9 ICUs during an 11-year period.

Results

Data of 248 patients (mean age = 62.4 ± 13.3 years; 63.7 % male) were studied. Native and prosthetic valves were involved in 195 and 53 patients, respectively. Causative pathogens, identified in 225 patients, were mainly streptococci (45.6 %) and staphylococci (43.4 %). On ICU admission, 127 patients exhibited extra-cardiac involvement. Ninety-five patients had one or more neurological complications, as followed: ischemic stroke (n = 66), cerebral hemorrhage (n = 31), meningitis (n = 16), brain abscess (n = 16), and intracranial mycotic aneurysm (n = 10). Criteria prompting to cardiac surgery appeared during ICU stay for 186 patients and between ICU and hospital discharges in 5 patients. Due to contra-indications, surgery required by IE was only performed during hospitalization in 125 patients. Moreover, surgery was considered adequate according to usual guidelines in 76 of 191 patients with indication(s) of valvular surgery: for patients with surgical procedure considered as emergency (n = 69), 17 surgical procedures underwent within the first 24 h following indication; for patients with urgent surgical indication (n = 102), surgery was performed during the first week following indication in 40 patients; finally, elective surgery (n = 20) was performed for 19 patients. During hospitalization, 103 (41.5 %) patients died. Four independent prognostic factors were identified: SAPS II > 35 (AOR = 2.604; 95 % CI: 1.320–5.136; p = 0.0058), SOFA > 8 (AOR = 3.327; 95 % CI: 1.697–6.521; p = 0.0005), IE due to methicillin resistant Staphylococcus aureus (AOR = 4.981; 95 %CI = 1.433–17.306; p = 0.0115) and native IE (AOR = 0.345; 95 % CI: 0.169–0.703; p = 0.0034).

Conclusions

Mortality in patients admitted to ICU for left-sided IE remains high, especially in cases of endocarditis due to methicillin resistant Staphylococcus aureus, when organ failures occur and ICU scores are high.

Keywords

Critical care medicineInfective endocarditisCardiac surgeryInfectious diseasesPrognostic

Background

The annual incidence of infective endocarditis (IE) in France at the beginning of the 21st century is around 33 cases per million inhabitants [1]. Despite advances in diagnosis and medico-surgical treatment, the in-hospital mortality rate remains high, since ranging from 15 to 22 % [13]. Most recent data underline that now Staphylococcus aureus is the most common cause of IE and that approximately 50 % of patients underwent early valve replacement or repair [2, 3].

Many complications can arise during the evolution of IE. Some are inaugural, the others come as the diagnosis has already been raised. Most of them can justify the admission of the patient in intensive care unit (ICU). Unfortunately, very few studies focused on patients with severe IE and multiple complications leading to ICU admission [47]. Therefore, we conducted a multicenter retrospective analysis of all consecutive critical left-sided IE patients to determinate characteristics of patients, in-hospital mortality and independent prognostic factors in the overall population.

Patients and methods

Study design and patients

In 9 ICUs of 7 hospitals (Boulogne sur Mer, Douai, Dunkerque, Valenciennes, Lille, Roubaix, and Tourcoing) in Nord-Pas de Calais, an area from North of France, the charts of all consecutive patients admitted to the ICU with a diagnosis of IE between January 2002 and December 2012 were reviewed (OL, HG, SBi, ND, CD, SBe, PDu, CBG and SP). Information collected from medical records was anonymously entered into a database and reviewed for data entry errors and/or inconsistencies (OL, HG, SBi and SP). In agreement with French regulations concerning observational studies that do not modify existing diagnosis or therapeutic strategies, no ethics committee approval was required to conduct the study.

Adult patients were enrolled in the study if they had a left-sided, definite, active and severe IE requiring ICU admission. IE involving mitral and/or aortic valves was defined as left-sided. Patients with both left- and right-sided IE and left-sided IE associated with infection of a cardiac implantable electronic device (CIED) were considered as left-sided IE. Definite IE was defined according to modified Duke criteria [8]. Endocarditis was defined as active if the patient was admitted in ICU before or within the first 30 days of antimicrobial treatment. IE was considered as severe when associated with any of the following criteria: acute respiratory failure requiring mechanical ventilation, shock, Simplified Acute Physiology Score (SAPS) II ≥20 and Sepsis-related Organ Failure Assessment (SOFA) score ≥3.

Patients with right-sided IE or infection of a cardiac implantable electronic device without left valves involvement were not included as well as patients with IE acquired during ICU stay, or admitted in ICU after valve surgery for IE and, finally, those with possible IE.

Data collection and definitions

For each patient, IE was diagnosed when required modified Duke criteria were obtained. As all these criteria could not be present on ICU admission, there may be a delay between ICU admission and IE diagnosis that was determined. When IE was diagnosed, we collected for each patient information about demographics, pre-existing comorbidities, condition at ICU admission, initial valve status, origin of infection, microbiological data, echocardiographic data, and extra-cardiac involvement revealed by initial work-up. As this study was retrospective, the initial work-up was not standardized and radiological examinations were performed at the discretion of physicians. During the ICU stay, the antimicrobial treatment, the occurrence of complications, indications for surgery, timing of surgical procedure were recorded. Finally, outcome was evaluated.

Underlying conditions were evaluated by the Charlson score [9]. Severity of illness at ICU admission was assessed by the SAPS II, and SOFA score [10, 11]. Prosthetic valve IE was defined as infection occurring on any type of tissue or mechanical device. Hospital-acquired IE was defined as infection occurring more than 72 h after admission to the hospital or acquired in association with a significant invasive procedure performed during a recent hospitalization within 8 weeks of this hospitalization [12]. Microbiological diagnosis was assessed according to modified Duke criteria. Echocardiographic data recorded were regurgitant valve, vegetation length and location. Follow-up examinations were performed to monitor vegetation size and to detect the occurrence of complications. Antimicrobial therapy was considered adequate if it included antibiotic(s) usually proposed by current guidelines [13]. IE complications on ICU admission such as congestive heart failure, septic shock, and extra-cardiac involvement mainly due to systemic embolic events were defined according to current guidelines [13]. For neurological involvement, five complications were distinguished according to the results of brain imaging (magnetic resonance imaging and/or computerized tomography scanning) and cerebrospinal fluid analyses performed on initial work-up: ischemic stroke, cerebral hemorrhage, meningitis or meningeal reaction, brain abscess, and intracranial mycotic aneurysm.

Indications (heart failure, prevention of embolic events and uncontrolled infection) and timing of surgery (emergency, urgent and elective) were defined by current guidelines [13]. Surgery was considered adequate when surgical procedure was performed accordingly to such guidelines. In-hospital mortality was defined as death occurring within the same hospitalization as ICU admission, regardless of its cause.

Statistical analysis

Descriptive analyses were performed to check and summarize the data. Quantitative variables are reported as mean ± standard deviation. Qualitative variables are reported as number and percentage. Continuous variables were compared using the Student’s t test. Categorical variables were compared using the Chi-square test or Fisher’s exact test when Chi square was not appropriate. Differences between groups were considered to be significant for variables yielding a p value ≤0.05. A stepwise logistic regression analysis was performed to identify risk factors associated with in-hospital mortality, regardless of its cause. In order to identify independent risk factors for mortality, variables were included in the multivariate model if the p value was ≤0.05 in bivariate analysis. Adjusted odds ratios (AOR) were computed using logistic regression analysis including the independent predictors of mortality.

All statistical analyses were performed using SAS software, V9.1.

Results

During the study period, 352 patients with IE were admitted in one of the 9 ICUs of our group. We excluded 104 patients for the following reasons: right-sided IE or infection of a cardiac implantable electronic device without left valves involvement (n = 41); diagnosis of IE non definite (n = 34); non severe IE (n = 24); IE acquired during ICU stay (n = 5). Finally, 248 patients with severe, active, definite and left-sided IE were studied. Among them, two IE major criteria were present in 232 patients and one major criterion with 2 or 3 minor criteria was present in the remaining 16 patients. One hundred forty-eight (59.7 %) patients were admitted in a tertiary care hospital with a cardiac surgery department (Lille) and 100 (40.3 %) were admitted in a general hospital without any cardiac surgery department. The mean delay between ICU admission and IE diagnosis was 1.75 ± 3.74 days. Main patients’ characteristics on ICU admission and on IE diagnosis are summarized in Table 1.
Table 1

Main patients’ characteristics on ICU admission and on IE diagnosis

Patients’ characteristics

 

Age (years)

62.4 ± 13.3

Sex: M/F

158/90

Charlson score

4.58 ± 2.70

SAPS II

36.7 ± 16.7

SOFA score

7.0 ± 3.7

Main indications for ICU admission

 Septic shock

54 (21.8)

 Severe valvular regurgitation

46 (18.55)

 Cardiogenic shock

39 (15.7)

 Acute renal failure

36 (14.5)

 Acute respiratory failure requiring mechanical ventilation

28 (11.3)

 Neurological complications

17 (6.85)

Community-acquired/hospital-acquired IE

215 (86.7)/33 (13.3)

Native valve/prosthetic valve IE

195 (78.6)/53 (21.4)

Valve involvement

 Aortic

156

 Mitral

152

 Tricuspid

9

 Pulmonary

1

 Multiple valve involvement

66

  Aortic plus mitral valves

53

  Aortic plus tricuspid valves

3

  Aortic plus pulmonary valves

1

  Aortic plus mitral plus tricuspid valves plus CIED

1

  Aortic plus mitral valves plus CIED

3

  Aortic valve plus CIED

1

  Mitral plus tricuspid valves

3

  Mitral plus tricuspid valves plus CIED

1

Portal of entry of IE

126 (50.8)

 Skin or soft tissue

36

 Dental

24

 Upper respiratory tract

9

 Genitourinary tract

13

 Digestive tract

23

 Intra-venous drug abuse

2

 Cardiovascular procedure or vascular access

19

The results are given as n (%) or median ± SD

When indicated SAPS II Simplified Acute Physiologic Score II, SOFA sepsis-related organ failure assessment score, CIED cardiac implantable electronic device

Echocardiographic examinations revealed mitral vegetation(s) in 137 patients. Vegetations were large (>10 mm) in 67 patients and very large (>15 mm) in 41 patients. Mitral regurgitation was severe (3 to 4+) in 56 patients. One hundred and twenty-three patients exhibited aortic vegetation(s). They were large and very large in 51 and 24 patients, respectively. Aortic regurgitation was severe in 66 patients. An annular abscess was observed in 67 patients. Six patients had a pericardial effusion. Finally, the mean value of left ventricular ejection fraction was 55.0 ± 11.6 %. It was <35 % in 16 patients, >35 % and <50 % in 82, >50 % in 144, and finally not determined in 6.

Causative pathogen was identified in 225 (90.7 %) patients. Blood and leaflet cultures were positive in 222 and 25 cases, respectively. Two hundred and thirty-five causative pathogens were identified. IE was polymicrobial in 9 patients. The most common pathogens were streptococci (45.6 %), and staphylococci (43.4 %) (Table 2).
Table 2

Causative microorganisms (n = 235) isolated from cases of active IE

Micro organism

N (%)

Streptococcus spp.

107 (45.6)

 Beta-haemolytic Streptococcus (groups A, B, C and G)

27

 Oral Streptococcus

24

 Enterococcus spp.

24

 Group D Streptococcus

19

 Streptococcus pneumoniae

13

Staphylococcus aureus

90 (38.3)

 Methicillin-susceptible

74

 Methicillin-resistant

16

Coagulase-negative Staphylococcus

12 (5.1)

Gram-negative bacilli

14 (6.0)

 Haemophilus influenzae

2

 Enterobacteriaceae

11

 Pasteurella multocida

1

Gram positive bacilli

1 (0.4)

Candida spp. and Aspergillus spp.

4 (1.7)

Other

7 (3.05)

On ICU admission and during the initial course of IE, 127 patients (51.2 %) exhibited extra-cardiac involvement. Main involved organ was the central nervous system. According to neurological investigations performed on 184 patients (74.2 %) (computerized tomography scanning n = 160, magnetic resonance imaging, and cerebrospinal fluid analyses n = 25), 139 neurological complications were found in 95 patients, as followed: ischemic stroke (n = 66), cerebral hemorrhage (n = 31), meningitis (n = 16), brain abscess (n = 16), and intracranial mycotic aneurysm (n = 10). Moreover, according to chest (n = 105), bone (n = 75) and abdominal (n = 144) computerized tomography scans, abdominal ultrasonography (n = 34), lung (n = 8) and bone (n = 13) scans, and bone magnetic resonance imaging (n = 24), systemic embolic or metastatic infective events involving spleen (n = 33), bone and joints (n = 22), kidneys (n = 21), lung (n = 3) and liver (n = 3) were found.

All patients received an antimicrobial treatment. This treatment was adequate in 206 (83.1 %) patients. During ICU stay, surgery was indicated for 186 (75 %) patients. The timing of surgical procedure was considered as emergency in 69 (37.1 %) patients, urgent in 102 (54.9 %) patients and elective in 15 (8 %) patients. Main indications and contra-indications for surgery are summarized in Table 3. Surgery was performed in 99 patients during the ICU stay (Table 4). Among the 101 patients without contra-indications to surgery, 84 (83.2 %) patients underwent surgery during ICU stay. Among the 85 patients with contra-indications, surgery was nonetheless performed in 15 (17.6 %) patients. In these latter patients, contra-indications were hemorrhagic stroke (n = 10), multiple organ failure (n = 3) and severe underlying diseases (n = 2). It could be noticed that only two of them, exhibiting multiple organ failure, died. Moreover, 21 patients with surgery indicated during ICU stay and 5 patients with ultimately appeared indication underwent surgical procedure between ICU and hospital discharges. Thus, during hospitalization, a surgical procedure was required by IE in 191 patients and was performed for 125 patients. Surgical procedure was required more often for patients admitted in a tertiary care hospital with a cardiac surgery department (n = 127/148) than for admitted in a general hospital without any cardiac surgery department (n = 64/100) (p < 0.001).
Table 3

Main Indications and contra-indications for valvular surgery during ICU stay

Timing of surgery

Indications

Number of patients with contra-indications

Contra-indications

Emergency n = 69

Cardiogenic shock n = 41

Refractory pulmonary oedema n = 28

33 (47.8 %)

Multiple organ failure n = 16

Hemorrhagic stroke n = 8

Severe underlying diseases n = 7

Risk of extra cerebral hemorrhage n = 2

Urgent n = 102

Very large vegetations = 43

Large vegetations and embolic episodes n = 21

Annular abscess n = 27

Uncontrolled infection n = 8

Severe acute regurgitation n = 3

50 (49 %)

Risk of cerebral hemorrhage n = 22

Multiple organ failure n = 16

Severe underlying diseases n = 11

Risk of extra cerebral haemorrhage n = 1

Elective n = 15

Severe regurgitation without heart failure n = 12

Severe prosthetic dehiscence n = 3

2 (13.3 %)

Severe underlying diseases n = 1

Multiple organ failure n = 1

Table 4

In hospital mortality according to surgery during ICU stay and in-hospital mortality

Timing of surgery

Number of patients

Number of patients with surgery performed during ICU stay

In hospital mortality n (%)

Number of patients with surgery not performed during ICU stay

In hospital mortality n (%)

Patients with contra-indications to surgery n = 85

 Emergency

33

6

1 (16.7 %)

27

25 (92.6 %)

 Urgent

50

8

1 (12.5 %)

42

30 (71.4 %)

 Elective

2

1

0

1

0

Patients without contra-indications to surgery n = 101

 Emergency

36

36

6 (16.6 %)

0

0

 Urgent

52

41

11 (21.2 %)

11

0

 Elective

13

7

0

6

2 (33.3 %)

For patients with surgical procedure considered as emergency (n = 69), 17 surgical procedure underwent within the first 24 h following indication. For patients with urgent surgical indication (n = 102), surgery was performed during the first week following indication in 40 patients. Finally elective surgery (n = 20) was performed for 19 patients. So, surgery was considered adequate according to usual guidelines in 76 of 191 (39.8 %) patients with indication(s) of valvular surgery. Surgery was more often adequate for patients admitted in a tertiary care hospital with a cardiac surgery department (n = 57/127) than for patients in a general hospital without any cardiac surgery department (n = 19/64) (p < 0.001).

During hospitalization, 103 (41.5 %) patients died. Main significant factors associated with in-hospital mortality in bivariate analysis are reported in Table 5. Factors assessing severity of underlying diseases and/or IE on ICU admission were associated with a significant increased mortality as well as prosthetic and staphylococcal IE. Conversely, native IE, IE due to Streptococcus and therapeutic measures such as surgery during ICU stay, adequate surgery and adequate antimicrobial treatment were associated with a significant decreased mortality. Multivariate analysis including all significant variables in bivariate analysis (p < 0.05), except surgery during ICU stay, surgery (overall) and adequate surgery, identified 4 independent prognostic factors. They were SAPS II > 35 (AOR = 2.604; 95 % CI: 1.320–5.136; p = 0.0058), SOFA > 8 (AOR = 3.327; 95 % CI: 1.697–6.521; p = 0.0005), IE due to methicillin resistant Staphylococcus aureus (AOR = 4.981; 95 %CI = 1.433–17.306; p = 0.0115) and native valve IE (AOR = 0.345; 95 % CI: 0.169–0.703; p = 0.0034).
Table 5

Bivariate analysis of risk factors for in-hospital mortality

Factor

Survivors n = 145

Non-survivors n = 103

p

Charlson score

4.18 ± 2.80

5.15 ± 2.46

0.003

SAPS II

30.99 ± 13.16

44.60 ± 17.95

<0.0001

SAPS II > 35

43 (38.4 %)

69 (61.6 %)

<0.0001

SOFA score

5.65 ± 2.77

8.93 ± 3.91

<0.0001

SOFA score >8

30 (33 %)

61 (67 %)

<0.0001

Glasgow Coma Score <9

7 (17.9 %)

32 (82.1 %)

<0.0001

ICU admission for septic shock

17 (31.5 %)

37 (68.5 %)

<0.0001

ICU admission for cardiogenic shock

16 (41 %)

23 (59 %)

0.016

ICU admission for acute respiratory failure

22 (78.6 %)

6 (21.4 %)

0.02

ICU admission for severe valvular regurgitation

40 (87 %)

6 (13 %)

<0.0001

Mitral IE

80 (52.6 %)

72 (47.4 %)

0.02

Native IE

121 (62.05 %)

74 (37.95 %)

0.03

Prosthetic IE

24 (45.3 %)

29 (54.7 %)

0.03

Annular abscess

31 (46.3 %)

36 (53.7 %)

0.02

Severe aortic regurgitation

50 (75.8 %)

16 (24.2 %)

0.0009

Left ventricular ejection fraction (%)

57 ± 11

52 ± 13

0.005

IE due to Streptococcus spp.

72 (67.3 %)

35 (32.7 %)

0.01

IE due to MSSA

36 (48.70 %)

38 (51.3 %)

0.04

IE due to MRSA

4 (25 %)

12 (75 %)

0.005

Adequate antimicrobial treatment

127 (61.7 %)

79 (38.3 %)

0.02

Surgery during ICU stay

80 (80.8 %)

19 (19.2 %)

<0.0001

Surgery (overall)

102 (81.6 %)

23 (18.4 %)

<0.0001

Adequate surgery

65 (85.5 %)

11 (14.5 %)

<0.0001

MSSA methicillin-susceptible Staphylococcus aureus, MRSA methicillin-resistant Staphylococcus aureus

To focus on the 16 patients with IE due to methicillin resistant Staphylococcus aureus, we could add that 12 had a native valve IE. Infection was hospital-acquired in 8 cases. Main portal of entry were skin or soft tissue (n = 4) and vascular access infections (n = 4). On ICU admission, the mean SAPS II was 44.6 ± 23.7 and 7 patients exhibited septic shock. Annular abscess was observed in 7 patients and neurological complications occurred in 7 patients. Antimicrobial treatment was considered inadequate in 4 patients (vancomycin without gentamicin in 2 cases of native valve IE and vancomycin + gentamicin without rifampin in 2 cases of prosthetic valve IE). Surgery was indicated for 11 patients (emergency n = 3; urgent n = 7; elective n = 1) but was adequate in only 3 patients. During hospitalization, 12 patients died (in ICU, n = 10).

Discussion

We report the results of a retrospective multicenter study on 248 patients with severe, active, definite and left-sided IE requiring ICU admission. Main causative pathogens are equally represented by streptococci and staphylococci. During ICU stay, surgery was indicated for 75 % of patients but only 53 % of them underwent surgical procedures during ICU stay. Overall in-hospital mortality was 41.5 %. Independent factors associated with prognosis were SAPS II on ICU admission >35, SOFA on ICU admission >8, IE due to methicillin resistant Staphylococcus aureus and native IE.

Current data suggest that staphylococci are the most common causative pathogens of IE. In the overall population of adults with definite IE admitted to hospital, S. aureus accounted for 26.6–36.2 % of causal agents [2, 14]. In series including only adult patients admitted to ICU with infective endocarditis, S. aureus represented 45–56 % of identified causative organisms [4, 7]. Our results could appear surprising since even if staphylococci are involved in 43.4 % of patients, they are less frequent causative organisms than streptococci involved in 45.6 % of patients. However, they are similar to those reported more than 10 years ago by Hoen et al. in France and Hasbun et al. in USA [15, 16]. In these series having included patients in 1999 and between 1990 and 2000, streptococci are involved in 48 and 58 %, respectively. We have no clear explanation about these microbiological differences between our study and those reporting data from patients admitted in ICU [4, 7]. Nevertheless, studied patients could be a little different. In the study from Mourvillier and colleagues, prosthetic valve IE are more frequent than in our series (40.6 vs. 21.4 %) and, if we focused only on native IE, streptococci and staphylococci are equally involved as causative organisms [4]. In the study reported by Samol and colleagues, 31 % of patients had right-sided endocarditis and it is well known that S. aureus is then the most common pathogen [7, 17].

In our study, a surgical procedure required by IE was performed during hospitalization for 125 patients (50.4 %). In series focusing on patients admitted to ICU for IE, 35–52 % of patients underwent surgery [4, 6, 7]. Rather than these gross percentages, an important point is, in our mind, the percentage of performed surgical procedures among patients for which indications for surgery emerge during ICU stay. Literature data are unfortunately scarce. In our series, surgery was indicated for 186 (75 %) patients but only 99 (53 %) of them underwent surgical procedures during ICU stay. In the study reported by Mirabel et al., the percentage appears higher since 100 of 158 patients with recommended surgical procedure underwent surgery [6]. Unfortunately, in this series, the timing of surgical procedure (emergency, urgent and elective) was only reported for patients undergoing surgery. So, it was not possible to determine the adequacy of surgery according to the timing, and consequently, to compare these results with ours. It’s a shame because it would have been interesting to known if the low percentage of adequate surgery observed in our series when timing was considered as emergency or urgent was also observed in other studies. In our series, it could be also noticed that among the 85 patients with contra-indications to surgery, 15 underwent nonetheless surgery and that 13 of them survived. Finally, surgery was more often adequate for patients admitted in a tertiary care hospital with a cardiac surgery department than for patients in a general hospital without any cardiac surgery department. Such a result reinforces recent recommendations for referring complicated IE patients to tertiary care hospitals in which a collaborative approach of IE involving notably a cardiac surgeon is possible [18].

The impact of surgery on IE prognosis was the subject of numerous studies. Despite some conflicting results, surgical therapy appears most often associated with an improved early and late survival both in the overall population of patients than in patients admitted to ICU [4, 6, 7, 1925]. In our series, in-hospital mortality was 41.5 %. In similar series, mortality rates varied between 30 and 45 %, and apart surgery, identified independent prognostic factors were septic shock, cerebral emboli, immunosuppression, neurological failure, severe comorbidities, S. aureus IE and SAPS II [4, 5, 7]. Most of these factors appear in our series as significant prognostic factors in bi variate analysis. Among them, we could notice that IE due to Streptococcus spp. were associated with a lower mortality than IE due to Staphylococcus spp. and that adequacy of antimicrobial and of surgical treatment also appeared as factors associated with survival. However, in our study, we willingly chose to not enter in multivariate analysis the significant factors about surgery identified in bivariate analysis (surgery during ICU stay, surgery and adequate surgery) since the overall population was not affected by these prognostic factors. Our multivariate analysis identified 4 independent factors. They were SAPS II > 35 (AOR = 2.604), SOFA > 8 (AOR = 3.327), IE due to methicillin resistant Staphylococcus aureus (AOR = 4.981) and native IE (AOR = 0.345). The fact that scores assessing severity and/or organ failure on ICU admission are independent prognostic factors is not surprising since they are usually found in all studies focusing on prognostic of ICU patients. The protective role of the native character of endocarditis is not, in our opinion, surprising since the deleterious role of the prosthetic character of endocarditis is well known [3]. In example, in the study reported by Murdoch et al. including 2781 patients from the International Collaboration on Endocarditis–Prospective Cohort Study, prosthetic valve involvement appears as an independent factor associated with mortality [2]. The deleterious role of an infection due to methicillin-resistant Staphylococcus aureus could appear more surprising since it has not yet been found in previous studies. However, in our opinion, it was not really studied. In the study reported by Murdoch, 869 patients exhibited a S. aureus IE but no data about sensitivity to methicillin was reported [2]. In a French study reporting data about 497 adults with Duke-Li–definite IE, 180 patients had a S. aureus IE [14]. Resistance to methicillin was observed in 13.6 % of S. aureus. Unfortunately, no data about impact of resistance to methicillin were provided. Finally, to the best of our knowledge, the study reported by Fowler et al. is one of the few studies providing prognostic data according to sensitivity to methicillin of S. aureus [26]. Among 1779 patients from the International Collaboration on Endocarditis–Prospective Cohort Study, the authors identified 424 patients with definite S aureus IE and no history of active IDU. Among them, 141 (33.3 %) were infected with methicillin resistant S. aureus. These patients tended to have higher mortality (29.8 vs. 23.3 %; p = 0.14) than those infected with a methicillin susceptible strain.

Our study has several limitations. First, all data were collected retrospectively. Second, it was a multicenter study. As a consequence of these 2 points, diagnostic methods, screening for complications and therapeutic measures were not standardized. Moreover, only one of the seven hospitals participating in the study had cardiac surgery units. It could thus be assumed that the access to cardiac surgery has not been the same for all patients, the most distant patients from surgical units being the least likely to benefit from emergency or urgent surgery. Similarly, a multidisciplinary approach could not be optimal for these later patients. Third, independent prognostic factors were identified by a stepwise logistic regression analysis. No case–control analysis was performed to evaluate the performance of identified factors. Fourth, our analysis was unable to establish a causal relationship between some therapeutic measures such as adequate antimicrobial treatment and survival. In a previous work, we demonstrated that such a treatment was an independent prognostic factor associated with survival [27]. Finally, we have only information on in-hospital mortality and long-term outcome was unknown.

In conclusion, mortality in patients admitted to ICU for left-sided IE remains high, especially in cases of endocarditis due to methicillin resistant Staphylococcus aureus and when organ failures occur and ICU scores are high.

Abbreviations

AOR: 

adjusted odds ratios

CI: 

confident interval

CIED: 

cardiac implantable electronic device

IE: 

infective endocarditis

ICU: 

intensive care unit

MSSA: 

methicillin-susceptible Staphylococcus aureus

MRSA: 

methicillin-resistant Staphylococcus aureus

SAPS II: 

simplified acute physiology score II

SD: 

standard deviation

SOFA: 

sequential organ failure assessment

Declarations

Authors’ contributions

FS and SP designed the study. OL, HG, SBi, ND, CD, SBe, PDu, CBG and SP collected data. PDe analyzed the data. OL, DT and SP wrote the article. All authors read and approved the final manuscript.

Competing interests

The authors declare that they have no competing interests.

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Authors’ Affiliations

(1)
Service de Réanimation Médicale et Maladies Infectieuses, Hôpital Chatiliez
(2)
Département de bio statistique, CHU de Lille
(3)
Pôle de Réanimation, Hôpital R. Salengro, CHU de Lille
(4)
Service de Réanimation Polyvalente, Centre Hospitalier Jean Bernard
(5)
Service de Réanimation Polyvalente, Hôpital Victor Provost
(6)
Service de Réanimation Polyvalente, Centre Hospitalier de Dunkerque
(7)
Service de Réanimation Polyvalente, Centre Hospitalier de Boulogne-sur-Mer
(8)
Service de Réanimation Polyvalente, Centre Hospitalier de Douai

References

  1. Duval X, Delahaye F, Alla F, Tattevin P, Obadia JF, Le Moing V, et al. Temporal trends in infective endocarditis in the context of prophylaxis guideline modifications: three successive population-based surveys. J Am Coll Cardiol. 2012. doi:10.1016/j.jacc.2012.02.029.PubMedGoogle Scholar
  2. Murdoch DR, Corey GR, Hoen B, Miró JM, Fowler VG Jr, Bayer AS, et al. Clinical presentation, etiology, and outcome of infective endocarditis in the 21st century: the International Collaboration on Endocarditis-Prospective Cohort Study. Arch Intern Med. 2009. doi:10.1001/archinternmed.2008.603.PubMed CentralPubMedGoogle Scholar
  3. Hoen B, Duval X. Infective endocarditis. N Engl J Med. 2013. doi:10.1056/NEJMc1307282.Google Scholar
  4. Mourvillier B, Trouillet JL, Timsit JF, Baudot J, Chastre J, Régnier B, et al. Infective endocarditis in the intensive care unit: clinical spectrum and prognostic factors in 228 consecutive patients. Intensive Care Med. 2004. doi:10.1007/s00134-004-2436-9.PubMedGoogle Scholar
  5. Sonneville R, Mirabel M, Hajage D, Tubach F, Vignon P, Perez P, et al. Neurologic complications and outcomes of infective endocarditis in critically ill patients: the ENDOcardite en REAnimation prospective multicenter study. Crit Care Med. 2011. doi:10.1097/CCM.0b013e3182120b41.Google Scholar
  6. Mirabel M, Sonneville R, Hajage D, Novy E, Tubach F, Vignon P, et al. Long-term outcomes and cardiac surgery in critically ill patients with infective endocarditis. Eur Heart J. 2014. doi:10.1093/eurheartj/eht303.PubMedGoogle Scholar
  7. Samol A, Kaese S, Bloch J, Görlich D, Peters G, Waltenberger J, et al. Infective endocarditis on ICU: risk factors, outcome and long-term follow-up. Infection. 2015. doi:10.1007/s15010-014-0715-0.PubMedGoogle Scholar
  8. Li JS, Sexton DJ, Mick N, Nettles R, Fowler VG Jr, Ryan T, et al. Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis. 2000;30:633–8.View ArticlePubMedGoogle Scholar
  9. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40:373–83.View ArticlePubMedGoogle Scholar
  10. Le Gall JR, Lemeshow S, Saulnier F. A new simplified acute physiology score (SAPS II) based on a European/North American multicenter study. JAMA. 1993;270:2957–63.View ArticlePubMedGoogle Scholar
  11. Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, et al. The SOFA (sepsis-related organ failure assessment) score to describe organ dysfunction/failure. Intensive Care Med. 1996;22:707–10.View ArticlePubMedGoogle Scholar
  12. Mouly S, Ruimy R, Launay O, Arnoult F, Brochet E, Trouillet JL, et al. The changing clinical aspects of infective endocarditis: descriptive review of 90 episodes in a French teaching hospital and risk factors for death. J Infect. 2002;45:246–56.View ArticlePubMedGoogle Scholar
  13. Habib G, Hoen B, Tornos P, Thuny F, Prendergast B, Vilacosta I, et al. Guidelines on the prevention, diagnosis, and treatment of infective endocarditis (new version 2009): the task force on the prevention, diagnosis, and treatment of infective endocarditis of the European Society of Cardiology (ESC). Endorsed by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and the International Society of Chemotherapy (ISC) for Infection and Cancer. Eur Heart J. 2009;30:2369–413.View ArticlePubMedGoogle Scholar
  14. Selton-Suty C, Célard M, Le Moing V, Doco-Lecompte T, Chirouze C, Iung B, et al. Preeminence of Staphylococcus aureus in infective endocarditis: a 1-year population-based survey. Clin Infect Dis. 2012. doi:10.1093/cid/cis199.PubMedGoogle Scholar
  15. Hoen B, Alla F, Selton-Suty C, Béguinot I, Bouvet A, Briançon S, et al. Changing profile of infective endocarditis: results of a 1-year survey in France. JAMA. 2002;288:75–81.View ArticlePubMedGoogle Scholar
  16. Hasbun R, Vikram HR, Barakat LA, Buenconsejo J, Quagliarello VJ. Complicated left-sided native valve endocarditis in adults: risk classification for mortality. JAMA. 2003;289:1933–40.View ArticlePubMedGoogle Scholar
  17. Akinosoglou K, Apostolakis E, Marangos M, Pasvol G. Native valve right sided infective endocarditis. Eur J Intern Med. 2013. doi:10.1016/j.ejim.2013.01.010.PubMedGoogle Scholar
  18. Habib G, Lancellotti P, Antunes MJ, Bongiorni MG, Casalta JP, Del Zotti F, et al. ESC Guidelines for the management of infective endocarditis. Eur Heart J. 2015. doi:10.1093/eurheartj/ehv319.Google Scholar
  19. Wolff M, Witchitz S, Chastang C, Régnier B, Vachon F. Prosthetic valve endocarditis in the ICU. Prognostic factors of overall survival in a series of 122 cases and consequences for treatment decision. Chest. 1995;108:688–94.View ArticlePubMedGoogle Scholar
  20. Wang A, Pappas P, Anstrom KJ, Abrutyn E, Fowler VG Jr, Hoen B, et al. The use and effect of surgical therapy for prosthetic valve infective endocarditis: a propensity analysis of a multicenter, international cohort. Am Heart J. 2005;150:1086–91.View ArticlePubMedGoogle Scholar
  21. Cabell CH, Abrutyn E, Fowler VG Jr, Hoen B, Miro JM, Corey GR, et al. Use of surgery in patients with native valve infective endocarditis: results from the International Collaboration on Endocarditis Merged Database. Am Heart J. 2005;150:1092–8.View ArticlePubMedGoogle Scholar
  22. Aksoy O, Sexton DJ, Wang A, Pappas PA, Kourany W, Chu V, et al. Early surgery in patients with infective endocarditis: a propensity score analysis. Clin Infect Dis. 2007;44:364–72.View ArticlePubMedGoogle Scholar
  23. Lalani T, Cabell CH, Benjamin DK, Lasca O, Naber C, Fowler VG Jr, et al. Analysis of the impact of early surgery on in-hospital mortality of native valve endocarditis: use of propensity score and instrumental variable methods to adjust for treatment-selection bias. Circulation. 2010. doi:10.1161/CIRCULATIONAHA.109.864488.PubMed CentralPubMedGoogle Scholar
  24. Thuny F, Beurtheret S, Mancini J, Gariboldi V, Casalta JP, Riberi A, et al. The timing of surgery influences mortality and morbidity in adults with severe complicated infective endocarditis: a propensity analysis. Eur Heart J. 2011. doi:10.1093/eurheartj/ehp089.PubMedGoogle Scholar
  25. Bannay A, Hoen B, Duval X, Obadia JF, Selton-Suty C, Le Moing V, 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. doi:10.1093/eurheartj/ehp008.PubMedGoogle Scholar
  26. Fowler VG Jr, Miro JM, Hoen B, Cabell CH, Abrutyn E, Rubinstein E, et al. Staphylococcus aureus endocarditis: a consequence of medical progress. JAMA. 2005;293:3012–21.View ArticlePubMedGoogle Scholar
  27. Fayad G, Vincentelli A, Leroy G, Devos P, Amr G, Prat A, et al. Impact of antimicrobial therapy on prognosis of patients requiring valve surgery during active infective endocarditis. J Thorac Cardiovasc Surg. 2014. doi:10.1016/j.jtcvs.2012.10.019.Google Scholar

Copyright

© Leroy et al. 2015

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