Clinical and pathogen features of infective endocarditis:A retrospective study of 111 episodes in a teaching hospital in southwest China

Background Infective endocarditis (IE) is a health-threaten infectious disease. Diverse and complicated etiology and causative microorganisms make IE dicult to diagnose and treat. As we know, current investigations of clinical and pathogen features of IE in West china are scarce. In this study, we aimed to investigate the epidemiology and pathogen characteristic of IE in our region. Methods A retrospective analysis of clinical and laboratory data was performed from all blood culture positive IE patients between 2012 to 2017 in Westchina Hospital of Sichuan University (cid:0) The diagnosis is traditionally based on the modied Duke criteria. Results The mean age of the patient cohort was 40.7±21.5 years (ranging from 2-78); 73 cases (65.2%) were males and 39 cases (34.8%) were females. Of the 111 cases, 100 were native valve endocarditis (NVE) while 11 were prosthetic valve endocarditis (PVE), 87 cases (78.4%) were left-heart infection. Congenital heart disease (28.6%) and rheumatic heart disease (11.6%) were most common history of heart disease. Primary clinical manifestations were fever (87.5%) and heart murmur (78.6%).Streptococci spp (20.7%) was the most common organism, followed by Staphylococcus spp(17.9%). Streptococcus viridians showed no resistance to penicillin, erythromycin and clindamycin resistance rate were 47.4% and 40%. Benzocillin resistance rate of staphylococcus aureus to was 26.3%. Vancomycin or linezolid resistance staphylococcus aureus were not found. 75 patients died while 36 patients survived at last. With respect to risk factors, history of heart disease was the only prognostic risk factor (OR: 0.239, 95%CI 0.08-0.68) Conclusions Epidemiological and clinical characteristics of infective endocarditis are various and complex, distribution of pathogen is regional difference. Our research of infective endocarditis with bloodstream infection veried regional characteristics of infective

common history of heart disease. Primary clinical manifestations were fever (87.5%) and heart murmur (78.6%).Streptococci spp (20.7%) was the most common organism, followed by Staphylococcus spp (17.9%). Streptococcus viridians showed no resistance to penicillin, erythromycin and clindamycin resistance rate were 47.4% and 40%. Benzocillin resistance rate of staphylococcus aureus to was 26.3%. Vancomycin or linezolid resistance staphylococcus aureus were not found. 75 patients died while 36 patients survived at last. With respect to risk factors, history of heart disease was the only prognostic risk factor (OR: 0.239, 95%CI 0.08-0.68) Conclusions Epidemiological and clinical characteristics of infective endocarditis are various and complex, distribution of pathogen is regional difference. Our research of infective endocarditis with bloodstream infection veri ed regional characteristics of infective endocarditis. The variations we observed in the study will be of important value to clinical preventive medication in our region.

Background
Infective Endocarditis (IE is an infection of heart valves or a ventricular endocardium caused by bacteria, fungus and other microorganisms, such as viruses, rickettsia, chlamydia, and spirochetes. As a rapid and reproducible method, blood culture is the best way to acquire pathogen in patients with IE. A new guideline for the management of IE was published by the Annual Congress of the European Society of Cardiology (ESC) in 2009 1 ,which shows regional differences in the clinical characteristics of endocarditis. As the most famous hospital in southwest China, Westchina hospital receives and treats patients of han nationality and ethnic minorities in southwest China. The types of patients have their own characteristics compared with other regions. Since there is no large retrospective study on regional epidemic characteristics in southwest China, purpose of this study was to investigate clinical characteristics of infective endocarditis and the epidemiological characteristics of pathogens in this region.

Study sample
A retrospective analysis was performed of clinical data collected from 111 cases clinically diagnosed IE with positive blood culture at Westchina Hospital of Sichuan University from Jan 2012 to Dec 2017. The data of retrospective analysis included general information, history of heart disease, clinical manifestations and laboratory ndings (taken at the time of rst presentation at the hospital), pathogen and outcome.

Statistical method
All data were analyzed using the SPSS version 21.0 software (SPSS, Chicago, IL, USA). P-values less than 0.05 were considered statistically signi cant.

Results
General characteristics. A total of 100 patients with NVE and 11 patients with PVE were included in our study.73 patients were male (65.2%) and 38 patients were female (34.8%). The mean age was 40.7±21.5 years, with a range from 12-78 years. 1 patient had a history of intravenous drug use(IDU).51 patients (46.4%) had history of heart disease, include 32 congenital heart disease (CHD), 13 rheumatic heart disease(RHD) 2 coronary artery disease(CAD) and 4 valvulopathy.4 cases were hospital acquire infection (3 cases were infection after ap replacement, 1 case was infection caused by streptococcus sepsis), the remaining 107 cases were community acquire infection. The most common symptom of IE patients was fever(87.5%),followed by cardiac murmurs(78.6%) . (Table 1 were right heart vegetations, including 12 cases of tricuspid valve vegetations 6 cases of pulmonary valve vegetations and 2 cases of mesh vegetation. Descending aortic vegetations were found in 1 patient and no vegetations were found in 4 patients. (Table 1) Among the 46 patients with aortic valve vegetation, 82.6% were associated with mild, moderate and severe aortic valve regurgitation (10 cases, 7 cases and 21 cases, respectively).Among the 36 cases of mitral valve vegetations, 75.0% were associated with mild, moderate and severe mitral regurgitation (4 cases, 11 cases and 12 cases, respectively).In the 12 cases with tricuspid valve vegetations, 75% of them were associated with moderate and severe tricuspid regurgitation, which were 3 cases and 6 cases respectively. Among the 5 cases of pulmonary valve vegetations, 1 was severe, 1 was moderate and 1 was mild re ux. Among the 5 patients with multiple valve excrescences, 1 patient had severe mitral regurgitation and 4 patients had multiple valve regurgitation. The other 8 cases were 2 cases of ventricular septal mesh vegetation,1 case of descending aorta vegetation and 1 case of left atrial wall vegetation, 4 cases of no vegetation and 5 cases of no re ux.( gure 1) it can be seen that although the damaged valves are different, they are all dominated by severe re ux, which has a great impact on heart function.

Results
General characteristics. A total of 100 patients with NVE and 11 patients with PVE were included in our study.73 patients were male (65.2%) and 38 patients were female (34.8%). The mean age was 40.7±21.5 years, with a range from 12-78 years. 1 patient had a history of intravenous drug use(IDU).51 patients (46.4%) had history of heart disease, include 32 congenital heart disease (CHD), 13 rheumatic heart disease(RHD) 2 coronary artery disease(CAD) and 4 valvulopathy.4 cases were hospital acquire infection (3 cases were infection after ap replacement, 1 case was infection caused by streptococcus sepsis), the remaining 107 cases were community acquire infection. The most common symptom of IE patients was fever(87.5%),followed by cardiac murmurs(78.6%) . (Table 1 (Table 1) Among the 46 patients with aortic valve vegetation, 82.6% were associated with mild, moderate and severe aortic valve regurgitation (10 cases, 7 cases and 21 cases, respectively).Among the 36 cases of mitral valve vegetations, 75.0% were associated with mild, moderate and severe mitral regurgitation (4 cases, 11 cases and 12 cases, respectively).In the 12 cases with tricuspid valve vegetations, 75% of them were associated with moderate and severe tricuspid regurgitation, which were 3 cases and 6 cases respectively. Among the 5 cases of pulmonary valve vegetations, 1 was severe, 1 was moderate and 1 was mild re ux. Among the 5 patients with multiple valve excrescences, 1 patient had severe mitral regurgitation and 4 patients had multiple valve regurgitation. The other 8 cases were 2 cases of ventricular septal mesh vegetation,1 case of descending aorta vegetation and 1 case of left atrial wall vegetation, 4 cases of no vegetation and 5 cases of no re ux.( gure 1) it can be seen that although the damaged valves are different, they are all dominated by severe re ux, which has a great impact on heart function.

Microbiological ndings.
Streptococci spp (59.5%) and Staphylococcus spp (25.2%) were the most common pathogen found in bloodstream of IE patients ( Table 2). Isolation rate of Streptococci spp is higher than Staphylococcus spp in 100 NVE patients, and Staphylococcus spp is higher than Streptococci spp in 11 prosthetic valve endocarditis patients(P<0.05).
Staphylococcus aureus has no sensitive to penicillin, resistance rate of erythromycin and clindamycin were 52.5% and 33.3%, resistance rate of other antibiotics were not more than 30%, methicillin-resistant Staphylococcus aureus (MRSA) was 26.3%. Coagulase negative staphylococcus (CNS) had no sensitive to penicillin and methicillin-resistant coagulase negative staphylococcus (MRCNS) was 75%, and resistance rate of other antibiotics was not exceeding 30% (table 3). Resistance rate of Streptococcus viridans and streptococcus angina to erythromycin, azithromycin, clindamycin and tetracycline were over 30 %. ( table 4). Gram-Negative strains were only 7 cases and no statistical signi cance could be found.

Prognosis
At last, 75 patients survived and 36 patients died In 111 patients of our study. Using a logistic regression analysis, we determined that history of heart disease was the only prognostic risk factors (OR: 0.239,95%CI 0.08-0.68)(table 5)

Discussion
The incidence rate of IE is between 2-7.9 per 100,000 people 2, 3 , and has remained stable 4 . Although relatively rare, IE continues to be characterized by increased morbidity and mortality and is now the third or fourth most common life-threatening infection syndrome. 5 In 2010, IE was associated with 1.58 million disability-adjusted life-years or years of healthy life lost, as a result of death and nonfatal illness or impairment worldwide 6 . The demographics of patients affected by IE have shifted in recent years, with an increase in mean patient age, an increase in the proportion of patients with prosthetic valves and other cardiac devices, and a decrease in the proportion of patients with rheumatic heart disease 6, 7 . The average age of the patients in this study was 40.7 years old, 49.1% of the patients were over 40 years old, and 65.2% of the patients were male and congenital heart disease (CHD) is the most common cardiac disease history that showed in IE patients, a same idea we could nd in the research of Fefer P, which considered no-rheumatic valvular heart disease of the elderly was the most common underlying factor. 8 In this study lung infection is the leading clinical features in IE patients without heart disease history,. It was similar to the studies of Aylin Tugcu. 9 .Electrocardiogram showed that valvular vegetations were mainly generated in the left heart, and most of them were accompanied with varying degrees regurgitation. Some infectious markers, such as CRP, erythrocyte sedimentation rate, and neutrophil, may contribute to early detection of the disease. 10 In this study, more than 50% patients accompany with WBC, N% ESR, PCT and CRP increased , infectious indicators may be used as an auxiliary basis for the diagnosis of infective endocarditis 4, 11. .However, due to the poor speci city of various infectious indicators 4 , pathogen culture and electrocardiogram are required as the nal basis for the diagnosis of IE 12 Staphylococcus spp is the most common cause of IE, followed by Streptococci spp 13,14 .Staphylococcus spp associate IE has became increasingly common in most industrialized countries because of increased medical intervention 5 ; meanwhile Streptococci spp has became less 15,16 . the presence of S. aureus bacteremia should be considered a major criterion, regardless of whether the infection is nosocomially acquired or whether a removable source of infection is present 17 . In the studies from Spain 18 , more than one third of IE cases were related to medical treatment, and the main pathogen of these patients was staphylococcus, however, pathogens may vary in different areas. 11,19,20 . in our study, the most common pathogen was Streptococcus viridans (20.7%), followed by staphylococcus aureus 18.0%.This prevalence pattern differs signi cantly from studies before. This may be related to economic development 21 . Patients of our research selected crowd in the southwest China where economic level and medical conditions is weak 5 , few patients had medical treatment. Study from Jerusalem 22 shows that staphylococcus often exists in medical care IE patients while more streptococci is found from community infection. Study from Lauren Hartman et al. showed that 23 staphylococcus aureus is the most common in patients with IDU-IE, while streptococcus is more common in patients without IDU-IE, only 1 patient had IDU history In our study. Above may be the reasons for the difference in distribution of pathogens. It is also reported21 that this difference may be due to adhesion molecules from Streptococcus viridans and staphylococcus aureus, which are related to the presence of surface adhesion factors on valve surfaces or in favor of bacterial colonization.
Indicate in European endocarditis management guidance, only for part of patients with congenital heart disease or valvular surgery, preventive use of antibiotics was necessary,10 Empirical treatment may include vancomycin or ampicillin/ Sulbactam and aminoglycosides24, but ultimately antibiotic treatment options need to be based on antibiotic sensitive test. In this study, neither staphylococcus nor streptococcus showed resistance to vancomycin, vancomycin could be used as a preventive treatment antibiotic. The resistance rate of staphylococcus and streptococcus to erythromycin, azithromycin, clindamycin and tetracycline are all over 30%, and it is not recommended to use in the experience of treatment.
To further explore the impact of the major death factors, the following information is included in the analysis model: gender, age ≥ 60 years, history of heart disease, PVE, Vegetative site and some lab data. Our results indicates that only history of heart disease is major risk factors for the prognosis of IE patients(OR:0.01,95%CI:0.08-0.68),while some study indicated that age ≥ 60 years (OR = 6.861, 0.94-50.1), congestive heart failure (OR = 8.854, 1.34-54.7), diabetes (OR = 7.224, 1.17-44.7), and Staphylococcus aureus or negative tuberculosis infection (OR = 18.81, 2.39-148.2) were major risk factors for the prognosis of IE patients. 21 This may be related to regional differences in studies.

Conclusions
Our study summarized the clinical and pathogenic characteristics of endocarditis patients in southwest China, and found that history of cardiac disease has an impact on the prognosis of patients

Consent for publication Not applicable
Availability of data and materials Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.
Competing interests the authors declare that they have no competing interests Funding These authors received no speci c grant from any founding agency in the public, commercial, ornot-for-pro t sectors.   Table 5 Death risk factor analysis in IE patients Figure 1 Blood re ux of Infective endocarditis patients.