Introduction

Infective endocarditis (IE) is a relatively rare but serious and life-threatening condition characterized by infection of the endocardial surface of the heart [1,2,3]. Despite progress, the diagnosis of IE is still challenging and outcomes are associated with substantial mortality and morbidity [4]. The mortality rate of treated IE patients after 30 days of admission is approximately 20%, with higher mortality rates among the elderly [5]. In the United States, the incidence of IE has risen steadily from 15 cases per 100,000 people per year in 2000 to 26 cases per 100,000 people per year [6].

In the past few decades, developed countries have seen a major shift in the etiology of IE, with rheumatic heart diseases (RHD) becoming a less common etiology for IE whereas other etiologies such as degenerative valve diseases, intravenous drug use, prior valve replacements, mitral valve prolapse, and indwelling catheters are becoming more common [7,8,9,10]. In addition, several factors including chronic kidney disease, cancer, human immunodeficiency virus (HIV), and using health care systems [5, 8, 11, 12] were associated with an increase in the infective endocarditis risk. Furthermore, the shift in the etiologies of IE has resulted in a shift in the causative organisms, as the incidence of Staphylococcus aureus, enterococcus, Gram-negative bacteria, and fungi has increased, while the incidence of Streptococcus viridans has decreased [6, 13, 14].

IE diagnosis is based on the modified Duke criteria, which comprise major and minor criteria [10, 15]. The major criteria include positive blood culture for an organism known to cause IE and evidence of endocardial involvement provided by echocardiography. The minor criteria include predisposing factors for IE, temperature > 38.0 °C, any of the IE vascular and immunological phenomena, and any positive culture not meeting the major criteria [15]. The treatment of IE depends mainly on prompt administration of intravenous antibiotics, while surgery has a role in the treatment of certain patients, especially those who present acutely with a high risk of developing heart failure and septic shock [3, 16].

Since ethnicity and genetic polymorphisms affect the susceptibility to IE, and due to the paucity of data in the middle east regarding IE, we decided to conduct this study aiming to investigate the epidemiology, clinical characteristics, microbiological profile, and outcomes of IE patients in a tertiary care facility in Jordan [17, 18].

Materials and methods

Design, setting, and patients

This is a retrospective case series conducted at the Jordan University Hospital (JUH), a tertiary medical center located in Amman, Jordan. All patients with a definite or possible IE diagnosis according to the modified Duke criteria in the period between January 2011 and February 2022 were eligible to be included in this study. The study was approved by the JUH Institutional Review Board (IRB) and was conducted in concordance with the declaration of Helsinki (IRB number: 10/2021/9424).

Data collection

A search for infective endocarditis cases was conducted among the JUH electronic medical records using the International Classification of Disease (ICD-10-CM) code for infective endocarditis (I33.0). This resulted in 98 medical records and 23 patients were finally included. Any patient who did not meet the modified Duke criteria was excluded. The following variables were collected for the included patients; age, gender, comorbidities, drug history, clinical presentation, blood culture results, echocardiographic findings provided by the radiology department reports, methods of treatment used for those patients, and patients’ 30-day outcomes.

Statistical analysis

IBM SPSS version 23 (IBM Corp., Armonk, NY, USA) was used to provide a descriptive analysis of the data in the form of frequencies and percentages for categorical variables and means and standard deviation for continuous variables.

Results

Characteristics of the included patients

Our study identified a total of 23 patients with infective endocarditis. The cohort had a mean age of 40.4 ± 20.96 years and 65.2% were males. The majority of patients had an underlying cardiac disease (60.9%), most commonly congenital heart diseases (17.4%). The other underlying cardiac diseases were prosthetic valves (13.0%), bicuspid aortic valves (13.0%), floppy valves (13.0%), and intracardiac devices (4.4%). Furthermore, 60.9% of the patients had comorbidities including hypertension (21.7%), diabetes (21.7%), and chronic kidney disease (17.4%).

Patients’ clinical presentation

The most common clinical presentation among the patients was fever (43.5%) defined as any reading ≥ 38 °C, followed by dyspnea and cough, which was found in 17.4% of the patients. The most common suspected port of infection was intravenous catheters (17.4%) followed by dental procedures (8.7%). Other suspected sources of infection were intracardiac devices and soft tissue infection. However, none of the patients in our study was abusing intravenous drugs or had had valve surgery within 2 months before the IE diagnosis (Table 1).

Table 1 Characteristics of 23 patients with infective endocarditis in the Jordan University Hospital
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The most commonly affected valves were the left-side heart valves, with the mitral valve (52.2%) being affected the most followed by the aortic valve (34.8%). Additionally, the tricuspid valves and pulmonary valves were involved in 17.4 and 8.7% of the cases, respectively. Involvement of mixed valves was present in 13% of the patients. The mixed valve combinations included aortic and mitral valves, aortic, mitral and pulmonary valves, and mitral and tricuspid valves (Table 1).

Microbiological characteristics and antibiotics used among the patients

The most common organism detected in blood culture was Streptococcus viridans (21.7%) followed by methicillin-resistant Staphylococcus aureus (MRSA). Other identified pathogens included Streptococcus bovis, Staphylococcus epidermis, enterococci, diphtheroid bacilli, micrococci, and Candida albicans. Moreover, negative culture presented in 34.8% of the patients’ cultures. Regarding treatment methods, 60.9% of the patients only required medical therapy, while 39.1% of the patients needed both medical and surgical treatment. The most common antibiotic regimens used were a combination of vancomycin, imipenem, gentamycin, and ceftriaxone.

Patient outcomes

The most common complications among the patients were heart failure and septic shock as they occurred in 21.7 and 17.4% of the patients, respectively. Other complications included cerebrovascular accidents, valvular damage, and splenic infarction (Table 2). The average length of stay in hospital was 25.86 ± 17.7 days and the mortality rate among the patients was 13% (Table 2). The mortality rates of patients managed medically and surgically were 14.2 and 11.1%, respectively.

Table 2 Microbiology, management, complications, and outcomes of infective endocarditis in the Jordan University Hospital
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In our cohort, 9 patients required a surgical intervention: 77.8% of them were males and the mean age was 37.7 ± 16.85 years. In addition, 44.4% of the patients had an underlying cardiac disease, with half of them having congenital heart disease and the other half having a bicuspid aortic valve. Only 3 patients had a suspected port of infection, which included an intravenous catheter, dental procedure, and skin/soft tissue infection. The organisms detected among those patients were Streptococcus viridans and MRSA in 2 patients each and Enterococcus and diphtheroid bacilli in 1 patient each, while a negative blood culture was found in 3 patients. Additionally, 6 of the 9 patients had prosthetic valve replacement while the rest had a mechanical valve (Table 3). All patients had a successful surgery and survived except one.

Table 3 Characteristics of 9 patients with infective endocarditis treated surgically
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Characteristics of patients who died due to IE

Among the study population, 3 patients died due to complications of IE. The first patient was a 74-year-old male who had several comorbidities including diabetes, hypertension, ischemic heart disease, chronic kidney disease needing hemodialysis, and complete heart block that required pacemaker previous to the incident of IE. The blood culture results showed Staphylococcus epidermidis growth, while the echocardiography revealed vegetations in the right atrium, the pacemaker, and the tricuspid valve. The patient did not need surgical intervention and died due to septic shock 30 days after hospitalization.

The second patient was a medically free 37-year-old female. The blood culture results showed Streptococcus viridans growth, whereas the echocardiography showed multi-valve involvement including the aortic, mitral, and tricuspid valves. The patient did not undergo any surgical intervention and died due to cardiac arrest at day 19 of hospitalization.

The third patient was a 1.5-year-old child who had a ventricular septal defect. The blood culture also showed Streptococcus viridans growth. Echocardiography revealed vegetations on the tricuspid valve with valve destruction. The patient underwent a surgical repair of the defect with removal of the vegetations. However, the patient developed postoperative intracerebral and intraventricular hemorrhages, acute kidney injury, and died 16 days after hospitalization (Table 4).

Table 4 Characteristics of in-hospital mortality cases
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Characteristics of patients who were diagnosed with IE during the COVID-19 pandemic

Among the study population, 5 patients were diagnosed with IE during the COVID-19 pandemic. Most of them (80%) were males, with a mean age of 55.4. Three of them had no identified port of infection. One patient had a dental procedure prior to his IE infection, and the last was found to have skin or soft tissue infection as a port of infection. The organisms detected among these patients were Streptococcus viridans, Streptococcus bovis, and Enterococcus in 3 separate patients, while a negative blood culture was found in 2 patients. The mitral valve was involved in all patients (100%). One of them was found to have aortic, mitral, and pulmonary valve involvement. Only one of the patients (20%) required surgical intervention, while the rest (80%) were treated medically. One of these patients died during the IE admission (Table 5).

Table 5 Characteristics of 5 patients with infective endocarditis diagnosed during COVID-19 pandemic period
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Discussion

This retrospective cohort summarizes the data of 23 patients diagnosed with IE through 10 years’ experience at a tertiary hospital in Jordan. The results showed a male predominance among the patients, which is similar to previous studies conducted in Saudi Arabia, Oman, and Lebanon. The mean age of the sample was 40.1 ± 20.96 years, which is considered younger than the mean age reported by studies conducted in Saudi Arabia, Qatar, and Lebanon, which showed mean ages of 48, 51, and 61 years, respectively [19,20,21]. This higher mean age in the developed countries compared to other developing countries was explained mainly by three factors, i.e., the increase in the proportion of elderly in the general population, the reduction in the incidence of rheumatic heart disease, and the relatively new emerging entity of health care-associated IE, which affects the elderly more [3]. Furthermore, around 60.9% of the patients in our cohort had an underlying cardiac disease as a risk factor, the most common of which were congenital heart diseases 17.4%. Moreover, 60.9% of the patients had at least one chronic disease, hypertension (21.7%), diabetes mellitus (21.7%), and chronic kidney disease (17.4%). The signs and symptoms of patients with IE in our study were highly variable, but the most common sign at the time of presentation was fever, which is similar to studies conducted in Saudi Arabia and Qatar that also reported the same finding [19, 20].

The yield of positive culture in our study was 65.2%, which is similar to what was reported in studies conducted in Saudi Arabia [19] and North India [22]. However, it is well known that only 10% of the blood cultures of patients with IE are negative. The high rate of negative cultures (34.8%) in our study can be explained by the fact that this study was conducted in a referral hospital, which means that a large proportion of the patients had received antibiotic therapy before the referral or the diagnostic workup [3]. Additionally, a frequently identified cause of negative culture is Coxiella burnetii, which is relatively common in the middle east due to the consumption of unpasteurized milk [23, 24]. Our study found that Streptococcus viridans was the most frequently identified microorganism among the patients with IE and accounted for 21.7% of the infections, which is similar to studies conducted in Oman, Lebanon, Kuwait, and Pakistan [25,26,27,28]. However, studies conducted in several developed countries showed that Staphylococcus species predominated in the study populations [3]. This difference in microorganisms between the countries was attributed to the shift in risk factors and etiologies of IE [3]. In addition, the increase in Staphylococcus prevalence was recently attributed to the emergence of health care-associated IE [3]. Moreover, MRSA was isolated in only 2 patients, which accounted for around 8.7% of our cohort. Previous studies showed similarly low rates of MRSA in IE patients in the Middle East that ranged between 2 and 7% [26, 29,30,31]. In contrast, it was reported that MRSA accounted for 14.8% of IE patients in the USA [32]. Moreover, the main difference between the Middle East and developed countries such as USA and European countries in the epidemiology of IE does not go beyond the microbiological etiology. Studies in the USA [32] and Europe [31] showed a higher prevalence of Staphylococcus aureus, especially MRSA, compared to our results and other studies results in the Middle East [19]. On the other hand, the demographic characteristics in these areas were quite similar to our results [31, 32]. Additionally, the mortality rate was similar to several countries in Europe such as Spain and England, which also reported a mortality rate of around 15%. Similar to the whole cohort, the analysis of the 5 patients diagnosed during the COVID-19 pandemic showed that in most of them, streptococcal species were the identifiable cause.

Echocardiography is considered the second cornerstone in the diagnosis of IE. The echocardiography results in our patients revealed that the most affected valves were mitral (52.2%) followed by the aortic valves (34.8%). These findings are similar to several studies conducted in Oman and Saudi Arabia [19, 28]. However, it is important to mention that recent studies have shown that the aortic valve has replaced the mitral one as the most commonly involved valve among patients with IE [33].

A surgical intervention was performed in 39.1% of our study patients, which is similar to the rates reported by studies conducted in Saudi Arabia, Tunisia, and the International Collaboration on Endocarditis prospective cohort study [23, 29, 34]. This high rate of surgical intervention indicates a lower threshold for early surgeries among IE patients than before [23]. Several studies showed that early surgery might be critical in lowering the mortality among patients with a definite IE diagnosis [35, 36]. Furthermore, it is important to mention that only 1 of the 9 patients who underwent surgical intervention in our study died.

The in-hospital mortality rate in our study was 13%. This mortality rate is within the range of rates reported by other studies, which ranged between 15 and 30% [23, 37, 38]. However, the mortality rate in our study was lower than those reported in Qatar, Saudi Arabia, and Oman, which reported rates of 29.4, 25, and 27.6%, respectively [20, 28, 39]. This low mortality rate can be explained by the fact that our cohort had younger mean age compared to the aforementioned studies, and it is established that age is a significant predictor for mortality [40]. Furthermore, patients diagnosed during the COVID-19 pandemic had a higher mortality rate than the whole cohort, at 20%. This can be explained by the delay in providing health care services during the COVID-19 pandemic, which might have resulted in more severe cases. Future studies are required to compare the morality rates of patients with IE between before the pandemic and during it [41].

This is the first study in Jordan to investigate the characteristics and outcomes of patients with IE. Although several studies have been conducted in the Middle East, data from the Middle East region are scarce. The differences in causes, microbiology profiles, and demographics between the regions is an important topic, as it can guide world policy-makers toward better worldwide policy guidance. Also, studies describing the profile of IE in different regions are important to guide physicians all over the world through the process of treatment and what to expect in foreign patients with IE such as immigrants and tourists. Finally, the difference in mortality rates between the pre-pandemic period and during the COVID-19 pandemic should guide researchers to investigate this topic further.

Limitations

This retrospective chart analysis had several limitations. First, the lack of electronic reporting before 2011 in Jordan University Hospital and the rarity of the disease resulted in a relatively small sample size. Second, the use of ICD codes for identifying cases with infective endocarditis might have resulted in missing some cases. Third, due to the small sample size, we were not able to identify prognostic factors associated with mortality. Moreover, data on serology and polymerase chain reaction tests for fastidious organisms such as Coxiella brunetti were not available in our study. Finally, JUH is a tertiary referral hospital; hence, the data we present in our study might not be representative for the general population of infective endocarditis patients and might be skewed toward patients with a more severe and progressive course of disease. Thus, we recommend establishing a national registry for IE patients.

Conclusion

This study describes the clinical features, complications, and management of patients with IE. Streptococcus viridans was the most frequent culture-isolated microorganism among IE patients. The presentation varied between patients, but the most common presentation was fever. Almost one third of our patients needed surgical intervention and the mortality rate was 13%.