Over the past decades, the epidemiology of IE has changed due to changes in demographic characteristics and risk factors. Researches from developed countries have showed that the incidence of IE has increased in the past decades [4]. Cresti et al. [9] found the incidence was 4.6/100,000 person-years with a significant linear increase between 1998 and 2014. Keller et al. [10] found that the incidence of IE in Germany was 11.6/100,000 person-years between 2005 and 2015, and the incidence increased continuously during the study period, especially in the last five years. However, in our study, we found that the incidence of IE was between 0.33 and 0.72 patients per 1000 admissions and the incidence remained stable during the period, which was lower in comparison with the developed countries (approximately 1-1.3 patients per 1000 hospital admissions) [4, 9] .The difference in incidence of IE from different studies may be related to the geographical location of the study, the time period selected, and the difference in diagnostic techniques of different institutions.
In our study, we found that the mean age at the time of IE episodes were younger than those reported from developed countries, although the mean age increased during this period. The proportion of old patients with IE increased gradually in this period, which was more obvious in developed countries [9, 11]. Erichsen et al. [12] found that the incidence increased substantially for elderly IE patients between 1994 and 2011, with the highest incidence rate of 3.38 for patients more than 80 years old at IE onset. In Oliver et al.’ s report [13], 49% of IE patients were over 65 years old and 11.2% were over 80 years old. The changes in the age of IE onset may owing to the aging population. And as a result of the older onset age, patients with IE in the latter part of the study period were more likely to have comorbidities compared with patients in the earlier part of the study period.
We found that CHD had become the most common underlying heart disease for patients with IE in our study. This result was consistent with other researches from China, where the proportion of CHD IE ranging from 20.1%-36.7% [14-16]. RHD once the most common underlying heart disease in the 1990s according to Chao et al.’ s report [17] was gradually decreasing in our study, which was consistent with other researches from China[6, 15, 16, 18]. These findings were some different from developed countries [6]. Researches from developed countries presented that DVD, PVE and implantable electronic devices related IE had gradually increased and replaced RHD as the leading heart disease[1, 4, 10].This difference may contributed to the late diagnosis for CHD , the low screening rate for newborn and the low proportion of surgical treatment when they were young in China[6].
According to Song Bing’s report [19], there were 35.6% patients diagnosed as CHD after 18 years old, and among patients with septal defect, 60.1% were diagnosed in adulthood, and only 6.7% were diagnosed in infancy. Data from Guangdong congenital heart defects monitoring network showed that the cumulative incidence of CHD in Guangdong province increased from 3.74 to 11.29 per thousand per year from 2004 to 2016 and the number of adult CHD gradually increased, although it currently accounts for only 21%, but the growth is nearly 18% [20]. According to Lai Xiaojin’s report [20] based on a 2356 cases analysis, the rate of adults with CHD has an increasing trend. The same phenomenon was seen from developed countries. This might due to that the symptoms and signs were not obviously during adolescence for some non-severe CHD, and they failed to be identified due to the restrictions of local medical and economic conditions in our region.
IE was an important complication for patients with CHD [21, 22]. According to the published reports, the risk of developing into IE increased in patients with CHD [21, 23, 24]. Darren et al.[24] found that the IE risk exceeded 100 times in patients with ACHD compared to that of the general population and 2.5 times that of children with CHD [24, 25].The proportion of patients with CHD in our study was as high as 25.8%.
TEE was performed in only 12.8% patients with IE in our study, as most patients diagnosed after TTE did not perform TEE routinely. Compared to the literature published from China on IE, the rate approached to other studies in our region [14-16]. But it was significantly lower than that reported by other studies from developed countries with 74%-100%[26,27].However, according to the 2015 European Association of Cardiology guidelines on IE , for TTE positive patients, TEE should be performed to exclude perivalvular complications[1]. The low utilization rate of TEE could directly resulted in the low detection rate of perivalvular complications such as valvular perforation and perivalvular abscess. Besides, this could cause the missed diagnoses of IE in patients with unobvious valvular lesions or with basic valvular lesions. This underlined that we still need to improve the use of TEE in IE diagnoses to reduce missed diagnoses.
The positive rate of blood culture in our study was lower compared with other studies from developed countries, where the rate of positive blood culture varied from 83% to 96%[2, 10, 13, 28] .However, the rate was approximate to other studies from China varied from 38.5%–70.1%[14, 15, 18].The low microbiology detection rate could be related to the extensive use of antibiotics before blood culture, and the proportion of patients with prior antibiotics use was as high as 81.7% in our study. Besides, as a tertiary hospital, most patients in our hospital had been referred from other medical institutions. They usually had a history of antibiotic treatment previous to the blood cultures. What’s more, the blood cultures of the HACEK group, serology tests for mycoplasma, bartonella, legionella and the polymerase chain reaction (PCR) were not performed in our hospital. Therefore, we suggested that patients with suspected bloodstream infection should receive blood cultures routinely before the use of antibiotics.
In our study, Streptococci was the main pathogen accounting for 24.6%, followed by Staphylococci accounting for 19.7%, and these were the same as reports in the 1990s from China [17]. This phenomenon was similar to other developing countries [5, 6] but was different from developed countries [4]. For IE in developed countries, the proportion of Staphylococci increased gradually and became the main pathogenic bacteria [4, 6].The increase in Staphylococcus IE was mainly due to the high incidence of intravenous drug addicts, hemodialysis patients and elderly patients with comorbidities [3, 4, 29, 30]. However, in our study, the proportion of patients with intravenous drug addicts, hemodialysis patients and octogenarians was lower compared with developed countries. Besides, most of patients in our study were community origin IE, and Streptococcus IE was the main for community origin IE according to the previous reports [16].
Enterococci IE was less common and the rate was stable in our study. This were consistent with another report from our region [18]. In this report, Enterococci was identified in 5 patients (2.9%) and the proportion was stable during 2008 to 2015[18]. However, this was quite different from developed countries [6]. In developed countries, Enterococci IE was more common and was the third leading cause of IE after Staphylococci and Streptococci ranging between 7-18% [9, 10, 28].According to the previous report, Enterococci IE was most frequently seen in elderly men with a relatively low short-term mortality [31].
According to the published studies, older age, prosthetic valve IE, heart failure, septic shock, Staphylococcus aureus, and large vegetation were predictors of poor outcome in patients with IE [1, 4]. In our study, we found that hemodialysis, pulmonary hypertension, Pitt score ≥ 4 and vegetation length＞30mm were independent risk factors for in-hospital mortality. The risk of in-hospital mortality in patients with hemodialysis increased by 4.697 times and in patients with pulmonary hypertension, the risk of in-hospital mortality increased by 5.308 times.
There are several limitations in our study. First, as a retrospective study, there exists information bias, and we are unable to obtain information on the patient exposure to dental procedures and the use of antibiotic prophylaxis. Second, the study used a single-center cohort in a tertiary teaching hospital with possible selection bias that could not represent the entire Chinese condition. Finally, as a nonrandomised study, there were associated limitations and selection bias affecting comparisons between the in-hospital outcomes. Therefore, we suggest multiple-center prospective cohort studies performed in our region.