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Journal of Infection and Public Health (2014) xxx, xxx—xxx
The epidemiology and outcomes of infective endocarditis in a tertiary care hospital in Oman Seif Salem Al Abri a,∗, Faisal Iqbal Zahedi b, Padmamohan J. Kurup c, Amina K. Al-Jardani d, Nicholas J. Beeching e a
Royal Hospital, P.O. Box 2657, CPO 111 Muscat, Oman Department of Medicine, Royal Hospital, Muscat, Oman c Regional epidemiologist, Muscat, Oman d Royal Hospital, Muscat, Oman e Liverpool School of Tropical Medicine, Liverpool, UK b
Received 28 October 2013 ; received in revised form 16 April 2014; accepted 18 April 2014
KEYWORDS Infective; Endocarditis; Epidemiology; Outcome; Oman
Summary Objectives: We undertook this study to describe the epidemiological and clinical features of infective endocarditis (IE) and to study the complications and management of IE in a tertiary care hospital in Oman. Methods: This is a retrospective study of 58 adult patients (>13 years of age) admitted to the Royal Hospital with IE from June 2006 to June 2011. Results: Of the 58 patients, 40 (69%) were males, and 18 (31%) were females (ratio 2.2). The median age was 43.6 years (range: 14—85). Forty-eight cases (82.7%) had native valves, nine patients (15.6%) had prosthetic valves, and one case (1.7%) had a pacemaker. The most commonly involved valves were mitral (33, 56.9%) and aortic (23, 39.7%). The blood cultures were positive in 47 (81%) patients, and the most commonly isolated organisms were Streptococci spp., which were found in 20 (34.5%) patients, and Staphylococci spp., which were found in 19 (32.8%) patients. The complication rate was 21%. A total of 15 (25.9%) patients underwent surgical intervention, and the in-hospital mortality rate was 27.6%.
∗
Corresponding author. Tel.: +968 99350255; fax: +968 24599966. E-mail addresses: [email protected] (S.S. Al Abri), [email protected] (F.I. Zahedi), [email protected] (P.J. Kurup), [email protected] (A.K. Al-Jardani), [email protected] (N.J. Beeching). http://dx.doi.org/10.1016/j.jiph.2014.04.004 1876-0341/© 2014 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Al Abri SS, et al. The epidemiology and outcomes of infective endocarditis in a tertiary care hospital in Oman. J Infect Public Health (2014), http://dx.doi.org/10.1016/j.jiph.2014.04.004
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S.S. Al Abri et al. Conclusions: Native-valve IE is the predominant type of endocarditis and is more of an acute disease. The prevalence of Staphylococci spp. IE is similar to that of Streptococci spp. IE, and its associated mortality remains high. © 2014 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.
Introduction
Methods
Over the past 30 years, the overall incidence of infective endocarditis (IE) in developed countries has remained between 2 and 6 per 100,000 individuals per year in the general population [1—3], and the associated mortality has remained between 10% and 30% depending on the type of pathogen, the underlying condition, and whether the infection occurred on a native or prosthetic heart valve [1]. The causative agents and the clinical presentation have changed considerably in recent years [4]. The main reason for this is the substantial modification in the conditions that predispose individuals to IE, such as a decline in the prevalence of rheumatic valvular disease, and a marked increase in the use of invasive diagnostic and therapeutic procedures [5]. In addition, intravenous drug use [6] and the older age of the patient population [7] have also influenced this shift. Although IE is generally fatal if left untreated [8], the availability of echocardiography and improvements in surgical techniques over the past years have substantially increased the diagnostic accuracy and treatment options for IE. More than half of IE patients suffer serious complications, and the mortality rate remains approximately 20% during initial hospitalization and approaches 40% at one year [9]. Descriptive data about IE and knowledge of the changing spectrum of this disease are helpful in determining the impact of the disease and to optimize its management. Data on IE prevalence, epidemiology and outcomes from Oman and the Gulf region are lacking, and the epidemiology of IE in this part of the world remains largely unknown. Apart from case reports of IE, there are only two studies from Saudi Arabia addressing the epidemiology of IE [10,11]. We undertook this study to describe the epidemiological and clinical features of IE and to study the complications and management of IE in a tertiary care hospital in Oman.
The Royal Hospital (RH) is a 650-bed tertiary care hospital serving the Muscat area and is also a referral hospital for cardiac surgery for patients from all over Oman, covering a population of approximately 3.5 million. This retrospective case study included all patients with a discharge diagnosis of IE from June 2006 to June 2011. The patients were identified from the computerized activity registers of the hospital, and all of the patients with a discharge code of IE (ICD 10-133.0) were included. The hospital case notes are fully computerized and were reviewed for all of the patients. The study was approved by the hospital ethics committee. Those found not to have IE were excluded from further analysis. The diagnosis of IE was based on the modified Dukes criteria [12]. A standard proforma was used to record the relevant data for the patients who were eligible. The data items encompassed the patient age and gender, admission year, length of hospital admission, underlying medical condition, anatomic site or device, symptoms at presentation, duration of symptoms before diagnosis, presence of heart murmur, results of chest radiography, transthoracic echocardiography (TTE) and/or transesophageal echocardiography (TEE) and blood cultures. We also recorded the initial choice of antibiotics after the diagnosis of IE, the duration of treatment, and the surgical treatment. In addition, we looked at the complications related to IE, mortality rates and outcomes. The data collected were entered into a database made using EpiData. The data analysis was performed using the SPSS 16.0 statistical package. The continuous variables were summarized by their mean values and standard deviation. The variables that were not normally distributed were summarized using their medians with interquartile ranges. The discrete variables were described using proportions. After a descriptive summary, the data were further analyzed to compare the clinical features
Please cite this article in press as: Al Abri SS, et al. The epidemiology and outcomes of infective endocarditis in a tertiary care hospital in Oman. J Infect Public Health (2014), http://dx.doi.org/10.1016/j.jiph.2014.04.004
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The epidemiology and outcomes of endocarditis and outcomes of prosthetic- and natural-valve IE. Student’s t-test was used for comparing the continuous variables, and the Chi-square test or Fisher’s exact test was used to compare discrete variables. All of the reported significance testing was twosided at the 0.05 significance level.
Results A total of 58 patients with IE were included in the study, and among them, one patient had two episodes of IE. The overall mean age of the patients was 43.6 years (range 14—85 years). Forty (69%) cases were in men, and 18 (31%) were in women. The median length of the hospital stay was 26 days. The most common comorbidities were hypertension (20.7%, 12), diabetes (17.2%, 10), presence of prosthetic valve (15.5%, 9), degenerative valve diseases (15.5%, 9), use of steroids and immunosuppressant drugs during the 30 days before admission to the hospital (15.5%, 9), mitral valve prolapse (13.8%, 8) and chronic renal failure (5.2%, 3). Fourteen (24%) patients had no known underlying medical conditions.
Clinical features Tables 1 and 2 summarize the data on valve involvement, clinical characteristics, complications and treatment of patients with IE. IE developed in a native valve in 48 (82.8%) cases, a mechanical prosthetic valve in nine (15.5%) cases, and a pacemaker in one (1.7%) case. None of the patients had early onset IE (infection that developed within one year of cardiac surgery). All of the symptoms and signs were nonspecific, and the most frequent symptoms at presentation were fever (52, 89.7%) and cough (15, 25.9%). The other symptoms were fatigue (11, 19%), shortness of breath (10, 17.2%), chest pain (10, 17.2%), confusion (8, 13.8%), sweating (7, 12.1%), myalgia (6, 10.3%), focal neurological deficit (6, 10.3%), headache (4, 6.9%), loss of appetite (4, 6.9%) and arthralgia (3, 5.2%). The median duration of symptoms before the diagnosis of IE was six days (interquartile range 2—21 days). A chest X-Ray was performed in 51/58 patients, and abnormal results were found in 28 of these patients (54.9%). Echocardiography was performed in all of the patients; TTE was performed in 55 IE patients, and 49 of these had positive findings. The six who presented negative results had positive results by TEE. TEE was performed in 35 of the patients, and
3 Table 1 Valve involvement, clinical characteristics, complications, and treatment of patients with IE. IVDA: intravenous drug abuse; CKD: chronic kidney disease.
Sex Male Female Valves involved Native Prosthetic Pacemaker Native valves Mitral Aortic Tricuspid Multiple (aortic and mitral = 5 and mitral and tricuspid = 1) Co-morbidities Hypertension Diabetes mellitus Degenerative valve disease Use of steroids and immunosuppressants within previous 30 days Mitral valve prolapse Previous right heart disease Congenital heart disease Hemodialysis IVDA Outcome/complications Complete recovery Death Hematuria CKD Stage 1 CKD Stage 2 CKD Stage 3A CKD Stage 3B CKD Stage 4 CKD Stage 5 Congestive heart failure Cerebrovascular accidents Embolic phenomenon Treatment Medical Surgical
N
%
40 18
69 31
48 9 1
82.7 15.6 1.7
21 14 6 6
42.9 28.6 12.2 12.2
12 10 9 9
20.7 17.2 15.5 15.5
8 7 5 3 3
13.8 12.1 8.6 5.2 5.2
34 16 30 16 7 4 6 5 1 14 4 3
58.6 27.6 51.7 27.6 12.1 6.9 10.3 8.6 1.7 24.1 6.9 5.2
43 15
74.1 25.9
all 35 patients presented positive findings. Thus, the sensitivity for detecting abnormalities in our IE patients was 49/55 (89.1%) with TTE and 35/35 (100%) for TEE. The site of anatomic involvement was as follows: the mitral valve in 33/58 (56.9%) cases, the aortic valve in 23 (39.7%) cases, the tricuspid valve in seven (12.1%) cases and the pacemaker in one case. Six patients had both aortic and mitral valve
Please cite this article in press as: Al Abri SS, et al. The epidemiology and outcomes of infective endocarditis in a tertiary care hospital in Oman. J Infect Public Health (2014), http://dx.doi.org/10.1016/j.jiph.2014.04.004
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S.S. Al Abri et al. Table 2 Clinical features and details of antibiotic treatment. eGFR: estimated glomerular filtration rate; CKD: chronic kidney disease. Characteristic
Summary statistic
Native valve (N = 49)
Prosthetic valve (N = 9)
Total (N = 58)
Age White blood count C-reactive protein (N = 55) ESR (N = 45) Serum albumin (N = 54) eGFR (N = 39) Length of stay Duration of antibiotic treatment Duration between onset of symptoms and start of treatment Duration of symptoms
Median (IQR) Mean (SD) Mean (SD) Mean (SD) Mean (SD) Mean (SD) Median (IQR) Median (IQR)
43 (25.5—58) 13.22 (17.7) 157.96 (117) 55.29 (32.9) 26.82 (6.7) 66.36 (28.6) 25 (14—40.5) 30 (21—42)
61 (35—66.5) 10 (5.6) 174.9 (180.3) 75 (47.4) 28.56 (5) 49.5 (18.5) 33 (10.5—45.5) 42 (36—49.5)
43.5 (26.8—59.3) 12.72 (16.5) 160.4 (126.2) 58.36 (35.6) 27.11 (6.4) 63.77 (27.8) 25.5 (14—41.3) 34.5 (22.5—42)
Median (IQR)
8 (3—20.75)
3 (1.5—10.5)
7 (2—17.5)
Median (IQR)
7 (2—21)
4 (2—12)
6 (2—21)
involvement, two patients had tricuspid and mitral valve involvement, and one patient had ventricular septal defects (VSD). Two patients had perivalvular abscess: coagulase-negative Staphylococci ssp. were isolated from one of these patients, and the culture from the other patient was negative. Serum albumin was measured in 54 of the patients, and the mean was found to be 27.1 g/l. The eGFR level was measured in 39 patients, and the mean was found to be 63.8 ml/min/1.73 m2 . Thirty (51%) of the patients had hematuria on urine microscopy. Blood cultures were taken from all of the patients, and Table 3 summarizes the overall culture results stratified by valve type. Overall, there were 47 (81%) positive cultures. The most commonly isolated organisms were Streptococci spp., which were found in 20 patients. The second most commonly isolated organisms were Staphylococci spp., which were found in 19 cases: 14 (24.1%) patients had methicillin-sensitive Staphylococcus aureus, four (6.9%) patients had coagulase-negative Staphylococci and one (1.7%) patient had methicillin-resistant S. aureus (MRSA). There were six (8.6%) cases of Enterococcus faecalis, two cases of E. coli, and two cases of Pseudomonas aeruginosa. In addition, Klebsialla pnemoniae, Bacteroides and Enterobacter were isolated in one patient each. Three patients presented the following combinations of two organisms: E. coli and Bacteroides, Streptococcus pneumoniae and coagulase-negative Staphylococci, and methicillin-sensitive Staphylococci and Streptococcus agalactiae. Eleven (19%) patients had negative blood cultures, and 10 of these patients had received antibiotics before blood collection.
Management and outcomes All of the patients received at least two intravenous antibiotics. The choice of antimicrobial agents was made on the basis of the culture results. Empirical antimicrobial therapy was used for culture-negative IE. The median duration of the antimicrobial therapy was 35 days (interquartile range 23—42 days). The patients who died were on antimicrobial therapy for 16 days with an IQR of 5—26 days, and the survivors were on antimicrobial therapy for a mean of 42 days with an IQR of 30—42 days. Surgery was performed in 15 (25.9%) patients, 10 of whom had prosthetic valves and five of whom had native valves. The most commonly encountered indications for surgery were heart failure (14 patients), large (>10 mm) mobile vegetations (4 patients), and valve dehiscence and root abscess (4 patients). Other indications for surgery included prosthetic-valve IE (1 patient), septic emboli to the lungs (1 patient), and the removal of a pacemaker (1 patient). Thirty-four patients exhibited complete recovery and were discharged from the hospital without any complications. Twenty-five (43%) patients had complications related to IE: 14 patients had heart failure, three patients had embolic phenomenon, and eight patients developed CVA. The in-hospital mortality rate was 27.6% (16 patients; 11 males and five females), and the mean age of the patients who died was 51.3 years.
Discussion There is a paucity of published data of infective endocarditis in Oman. The epidemiology of
Please cite this article in press as: Al Abri SS, et al. The epidemiology and outcomes of infective endocarditis in a tertiary care hospital in Oman. J Infect Public Health (2014), http://dx.doi.org/10.1016/j.jiph.2014.04.004
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Table 3 Microorganisms obtained from culture. MSSA: methicillin-sensitive Staphylococcus aureus; MRSA: methicillin-resistant Staphylococcus aureus; CNS: coagulase-negative Staphylococcus ssp. Organism
Native valves (N = 49)
Streptococci Staphylococci MSSA MRSA CNS Enterococci Pseudomonas aeruginosa E. coli Klebsiella pneumonia Bacteroides Enterobacter Negative culture Total number of cultures
17 (34.7%)
3 (33.3%)
20 (34.5%)
11(22.5%) 1 (2%) 4 (8.2%) 4 (8.2%) 2 (4.1%) 2 (4.1%) 1 (2%) 1 (2%) 1 (2%) 10 (20.4%) 54
3 (33.3%) 0 (0%) 2 (22.2%) 1 (11.1%) 0 0 0 0 0 1 (11.1%) 10
14 (24.1%) 1 (1.7%) 6 (10.3%) 5 (8.6%) 2 (3.4%) 2 (3.4%) 1 (1.7%) 1 (1.7%) 1 (1.7%) 11 (19%) 64
IE has shown some changes in the last 30 years [1,13]. The male-to-female ratio in our study is 2.2, which is in agreement with other published studies [14,15]. The mean age of the patients in our study is 43.6 years. This age group is older than the age groups from studies published in Saudi Arabia, Kuwait, India and Tunisia, which had mean ages between 28 and 32 years [10,14,16—18]. Other studies from Europe and the United States showed that 50% or more of the IE cases occurred in patients over the age of 50 years [5,14,19,20], and these studies have shown a steady increase in the median age. The mean age of the patients in a recent study from Saudi Arabia was 59.7 years [11]. In contrast, another recent study from Saudi Arabia showed a markedly lower mean age of 30 years [14]. This trend in developed countries is likely due to two factors: the increasing proportion of elderly people in the general population and the decline in the incidence of rheumatic heart diseases as a risk factor. Rheumatic heart disease and congenital heart diseases continue to be the most important causes of IE in the Middle East [10,13,15,21,22]. However, the most predisposing valvular conditions in our study were the presence of degenerative valve disease and prosthetic valves. Our findings reveal that IE is no longer a subacute or chronic condition: most of the patients’ symptoms were present for less than three weeks before the diagnosis of IE was made. Other published studies have report a more prolonged duration of symptoms before presentation [4,23]. Fever was the most prevalent symptom, occurring in 89.7% of the patients, similarly to the findings of other studies [14,15,24].
Prosthetic valves (N = 9)
Total (N = 58)
Most cases of IE involved native valves, and the mitral valve was the most commonly affected (56.9%), although the aortic valve was involved in 39.7% of the cases. These findings are similar to the results from two studies from Saudi Arabia [10,11]. However, some recently published studies have shown that the aortic valve has replaced the mitral valve as the most commonly infected site in IE [17,23,25]. Echocardiography was the mainstay of diagnosis in our patients. The sensitivity of TTE in this study was 89.1%, which is higher than the reported range of 50—75% from other studies [10]. TEE detected vegetations in six patients who were TTE-negative. The prevalence of Staphylococci spp. was equal to the prevalence of Streptococci spp. as a cause of IE, similarly to the results from recent studies from Turkey and Tunisia [15,18]. Recent studies have shown that Staphylococci spp. have overtaken Streptococci organisms as the most frequent causes of native-valve IE [5,10,11,14,24,26]. However, studies from Kuwait, Lebanon and Pakistan [21,22,27] showed a predominance of Streptococci spp. This difference is related to the time of the study because our study was performed at a more recent date. MRSA was isolated from only one patient, and other studies from Middle Eastern countries have shown similarly low rates, ranging from 3.7 to 7% [10,11,15,22]. This finding is much lower than the results from a study performed in the USA (14.8%) [28]. This shift is due in part to the global presence of risk factors for S. aureus-associated IE, such as healthcare contact and invasive procedures [29]. We noted a comparable proportion of subjects with culture-negative IE, similarly to studies from Saudi Arabia, Lebanon and Tunisia [10,11,18,21].
Please cite this article in press as: Al Abri SS, et al. The epidemiology and outcomes of infective endocarditis in a tertiary care hospital in Oman. J Infect Public Health (2014), http://dx.doi.org/10.1016/j.jiph.2014.04.004
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S.S. Al Abri et al.
Surgical intervention was performed in 25.9% of the cases, and this surgical rate is much lower than the 44.7% surgical rate reported from Saudi Arabia, the 50% surgical rate from Tunisia, and the 48.2% surgical rate reported by the International Collaboration on Endocarditis Prospective cohort study [10,14,16]. The high rate of surgical intervention indicates that the threshold for early surgical treatment is lower than before [14]. It has been shown that early surgery may be critical in improving survival in patients with definite IE [30—32]. Our data indicate that 43% of the patients experienced complications. All of the complications described in our study have been previously reported in the literature [14]. The in-hospital mortality in our study was 27.6%, which is within the mortality rate range of 15—30% reported in other case series [14,17,19]. There was no correlation between Staphylococci spp. IE and mortality in our study, even though some studies have shown an increased mortality rate, up to 40%, in patients infected with Staphylococci spp. IE [5,14]. We may have failed to identify other important prognostic factors because of the relatively small number of cases and the retrospective nature of the study. The prolonged duration of hospitalization in our cases, similar to that reported in other studies, denotes an important cost burden and a need for home or outpatient-based management whenever appropriate [33]. Our study has several limitations: it is retrospective and uncontrolled in design, and it is based on the discharge diagnosis. Serology and polymerase chain reaction tests for fastidious organisms, such as Brucella, Bartonella, Coxiella, and other rare causes of endocarditis were not performed. In addition, the Royal Hospital is a tertiary referral center, and our data may not truly represent endocarditis in the general community and may be skewed toward a more sick patient population. The study indicates the need to develop a national or regional IE registry throughout the Middle East. In conclusion, this study describes the clinical features, complications and management of IE. Native-valve IE is the predominant type of endocarditis and is more of an acute disease. The prevalence of Staphylococci spp. IE is similar to the prevalence of Streptococci spp. IE, and the IE morbidity and mortality rates remain high.
Conflict of interest Funding: No funding sources.
Competing interests: None declared. Ethical approval: Not required.
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Journal of Infection and Public Health (2014) xxx, xxx—xxx
The epidemiology and outcomes of infective endocarditis in a tertiary care hospital in Oman Seif Salem Al Abri a,∗, Faisal Iqbal Zahedi b, Padmamohan J. Kurup c, Amina K. Al-Jardani d, Nicholas J. Beeching e a
Royal Hospital, P.O. Box 2657, CPO 111 Muscat, Oman Department of Medicine, Royal Hospital, Muscat, Oman c Regional epidemiologist, Muscat, Oman d Royal Hospital, Muscat, Oman e Liverpool School of Tropical Medicine, Liverpool, UK b
Received 28 October 2013 ; received in revised form 16 April 2014; accepted 18 April 2014
KEYWORDS Infective; Endocarditis; Epidemiology; Outcome; Oman
Summary Objectives: We undertook this study to describe the epidemiological and clinical features of infective endocarditis (IE) and to study the complications and management of IE in a tertiary care hospital in Oman. Methods: This is a retrospective study of 58 adult patients (>13 years of age) admitted to the Royal Hospital with IE from June 2006 to June 2011. Results: Of the 58 patients, 40 (69%) were males, and 18 (31%) were females (ratio 2.2). The median age was 43.6 years (range: 14—85). Forty-eight cases (82.7%) had native valves, nine patients (15.6%) had prosthetic valves, and one case (1.7%) had a pacemaker. The most commonly involved valves were mitral (33, 56.9%) and aortic (23, 39.7%). The blood cultures were positive in 47 (81%) patients, and the most commonly isolated organisms were Streptococci spp., which were found in 20 (34.5%) patients, and Staphylococci spp., which were found in 19 (32.8%) patients. The complication rate was 21%. A total of 15 (25.9%) patients underwent surgical intervention, and the in-hospital mortality rate was 27.6%.
∗
Corresponding author. Tel.: +968 99350255; fax: +968 24599966. E-mail addresses: [email protected] (S.S. Al Abri), [email protected] (F.I. Zahedi), [email protected] (P.J. Kurup), [email protected] (A.K. Al-Jardani), [email protected] (N.J. Beeching). http://dx.doi.org/10.1016/j.jiph.2014.04.004 1876-0341/© 2014 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Al Abri SS, et al. The epidemiology and outcomes of infective endocarditis in a tertiary care hospital in Oman. J Infect Public Health (2014), http://dx.doi.org/10.1016/j.jiph.2014.04.004
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S.S. Al Abri et al. Conclusions: Native-valve IE is the predominant type of endocarditis and is more of an acute disease. The prevalence of Staphylococci spp. IE is similar to that of Streptococci spp. IE, and its associated mortality remains high. © 2014 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.
Introduction
Methods
Over the past 30 years, the overall incidence of infective endocarditis (IE) in developed countries has remained between 2 and 6 per 100,000 individuals per year in the general population [1—3], and the associated mortality has remained between 10% and 30% depending on the type of pathogen, the underlying condition, and whether the infection occurred on a native or prosthetic heart valve [1]. The causative agents and the clinical presentation have changed considerably in recent years [4]. The main reason for this is the substantial modification in the conditions that predispose individuals to IE, such as a decline in the prevalence of rheumatic valvular disease, and a marked increase in the use of invasive diagnostic and therapeutic procedures [5]. In addition, intravenous drug use [6] and the older age of the patient population [7] have also influenced this shift. Although IE is generally fatal if left untreated [8], the availability of echocardiography and improvements in surgical techniques over the past years have substantially increased the diagnostic accuracy and treatment options for IE. More than half of IE patients suffer serious complications, and the mortality rate remains approximately 20% during initial hospitalization and approaches 40% at one year [9]. Descriptive data about IE and knowledge of the changing spectrum of this disease are helpful in determining the impact of the disease and to optimize its management. Data on IE prevalence, epidemiology and outcomes from Oman and the Gulf region are lacking, and the epidemiology of IE in this part of the world remains largely unknown. Apart from case reports of IE, there are only two studies from Saudi Arabia addressing the epidemiology of IE [10,11]. We undertook this study to describe the epidemiological and clinical features of IE and to study the complications and management of IE in a tertiary care hospital in Oman.
The Royal Hospital (RH) is a 650-bed tertiary care hospital serving the Muscat area and is also a referral hospital for cardiac surgery for patients from all over Oman, covering a population of approximately 3.5 million. This retrospective case study included all patients with a discharge diagnosis of IE from June 2006 to June 2011. The patients were identified from the computerized activity registers of the hospital, and all of the patients with a discharge code of IE (ICD 10-133.0) were included. The hospital case notes are fully computerized and were reviewed for all of the patients. The study was approved by the hospital ethics committee. Those found not to have IE were excluded from further analysis. The diagnosis of IE was based on the modified Dukes criteria [12]. A standard proforma was used to record the relevant data for the patients who were eligible. The data items encompassed the patient age and gender, admission year, length of hospital admission, underlying medical condition, anatomic site or device, symptoms at presentation, duration of symptoms before diagnosis, presence of heart murmur, results of chest radiography, transthoracic echocardiography (TTE) and/or transesophageal echocardiography (TEE) and blood cultures. We also recorded the initial choice of antibiotics after the diagnosis of IE, the duration of treatment, and the surgical treatment. In addition, we looked at the complications related to IE, mortality rates and outcomes. The data collected were entered into a database made using EpiData. The data analysis was performed using the SPSS 16.0 statistical package. The continuous variables were summarized by their mean values and standard deviation. The variables that were not normally distributed were summarized using their medians with interquartile ranges. The discrete variables were described using proportions. After a descriptive summary, the data were further analyzed to compare the clinical features
Please cite this article in press as: Al Abri SS, et al. The epidemiology and outcomes of infective endocarditis in a tertiary care hospital in Oman. J Infect Public Health (2014), http://dx.doi.org/10.1016/j.jiph.2014.04.004
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The epidemiology and outcomes of endocarditis and outcomes of prosthetic- and natural-valve IE. Student’s t-test was used for comparing the continuous variables, and the Chi-square test or Fisher’s exact test was used to compare discrete variables. All of the reported significance testing was twosided at the 0.05 significance level.
Results A total of 58 patients with IE were included in the study, and among them, one patient had two episodes of IE. The overall mean age of the patients was 43.6 years (range 14—85 years). Forty (69%) cases were in men, and 18 (31%) were in women. The median length of the hospital stay was 26 days. The most common comorbidities were hypertension (20.7%, 12), diabetes (17.2%, 10), presence of prosthetic valve (15.5%, 9), degenerative valve diseases (15.5%, 9), use of steroids and immunosuppressant drugs during the 30 days before admission to the hospital (15.5%, 9), mitral valve prolapse (13.8%, 8) and chronic renal failure (5.2%, 3). Fourteen (24%) patients had no known underlying medical conditions.
Clinical features Tables 1 and 2 summarize the data on valve involvement, clinical characteristics, complications and treatment of patients with IE. IE developed in a native valve in 48 (82.8%) cases, a mechanical prosthetic valve in nine (15.5%) cases, and a pacemaker in one (1.7%) case. None of the patients had early onset IE (infection that developed within one year of cardiac surgery). All of the symptoms and signs were nonspecific, and the most frequent symptoms at presentation were fever (52, 89.7%) and cough (15, 25.9%). The other symptoms were fatigue (11, 19%), shortness of breath (10, 17.2%), chest pain (10, 17.2%), confusion (8, 13.8%), sweating (7, 12.1%), myalgia (6, 10.3%), focal neurological deficit (6, 10.3%), headache (4, 6.9%), loss of appetite (4, 6.9%) and arthralgia (3, 5.2%). The median duration of symptoms before the diagnosis of IE was six days (interquartile range 2—21 days). A chest X-Ray was performed in 51/58 patients, and abnormal results were found in 28 of these patients (54.9%). Echocardiography was performed in all of the patients; TTE was performed in 55 IE patients, and 49 of these had positive findings. The six who presented negative results had positive results by TEE. TEE was performed in 35 of the patients, and
3 Table 1 Valve involvement, clinical characteristics, complications, and treatment of patients with IE. IVDA: intravenous drug abuse; CKD: chronic kidney disease.
Sex Male Female Valves involved Native Prosthetic Pacemaker Native valves Mitral Aortic Tricuspid Multiple (aortic and mitral = 5 and mitral and tricuspid = 1) Co-morbidities Hypertension Diabetes mellitus Degenerative valve disease Use of steroids and immunosuppressants within previous 30 days Mitral valve prolapse Previous right heart disease Congenital heart disease Hemodialysis IVDA Outcome/complications Complete recovery Death Hematuria CKD Stage 1 CKD Stage 2 CKD Stage 3A CKD Stage 3B CKD Stage 4 CKD Stage 5 Congestive heart failure Cerebrovascular accidents Embolic phenomenon Treatment Medical Surgical
N
%
40 18
69 31
48 9 1
82.7 15.6 1.7
21 14 6 6
42.9 28.6 12.2 12.2
12 10 9 9
20.7 17.2 15.5 15.5
8 7 5 3 3
13.8 12.1 8.6 5.2 5.2
34 16 30 16 7 4 6 5 1 14 4 3
58.6 27.6 51.7 27.6 12.1 6.9 10.3 8.6 1.7 24.1 6.9 5.2
43 15
74.1 25.9
all 35 patients presented positive findings. Thus, the sensitivity for detecting abnormalities in our IE patients was 49/55 (89.1%) with TTE and 35/35 (100%) for TEE. The site of anatomic involvement was as follows: the mitral valve in 33/58 (56.9%) cases, the aortic valve in 23 (39.7%) cases, the tricuspid valve in seven (12.1%) cases and the pacemaker in one case. Six patients had both aortic and mitral valve
Please cite this article in press as: Al Abri SS, et al. The epidemiology and outcomes of infective endocarditis in a tertiary care hospital in Oman. J Infect Public Health (2014), http://dx.doi.org/10.1016/j.jiph.2014.04.004
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S.S. Al Abri et al. Table 2 Clinical features and details of antibiotic treatment. eGFR: estimated glomerular filtration rate; CKD: chronic kidney disease. Characteristic
Summary statistic
Native valve (N = 49)
Prosthetic valve (N = 9)
Total (N = 58)
Age White blood count C-reactive protein (N = 55) ESR (N = 45) Serum albumin (N = 54) eGFR (N = 39) Length of stay Duration of antibiotic treatment Duration between onset of symptoms and start of treatment Duration of symptoms
Median (IQR) Mean (SD) Mean (SD) Mean (SD) Mean (SD) Mean (SD) Median (IQR) Median (IQR)
43 (25.5—58) 13.22 (17.7) 157.96 (117) 55.29 (32.9) 26.82 (6.7) 66.36 (28.6) 25 (14—40.5) 30 (21—42)
61 (35—66.5) 10 (5.6) 174.9 (180.3) 75 (47.4) 28.56 (5) 49.5 (18.5) 33 (10.5—45.5) 42 (36—49.5)
43.5 (26.8—59.3) 12.72 (16.5) 160.4 (126.2) 58.36 (35.6) 27.11 (6.4) 63.77 (27.8) 25.5 (14—41.3) 34.5 (22.5—42)
Median (IQR)
8 (3—20.75)
3 (1.5—10.5)
7 (2—17.5)
Median (IQR)
7 (2—21)
4 (2—12)
6 (2—21)
involvement, two patients had tricuspid and mitral valve involvement, and one patient had ventricular septal defects (VSD). Two patients had perivalvular abscess: coagulase-negative Staphylococci ssp. were isolated from one of these patients, and the culture from the other patient was negative. Serum albumin was measured in 54 of the patients, and the mean was found to be 27.1 g/l. The eGFR level was measured in 39 patients, and the mean was found to be 63.8 ml/min/1.73 m2 . Thirty (51%) of the patients had hematuria on urine microscopy. Blood cultures were taken from all of the patients, and Table 3 summarizes the overall culture results stratified by valve type. Overall, there were 47 (81%) positive cultures. The most commonly isolated organisms were Streptococci spp., which were found in 20 patients. The second most commonly isolated organisms were Staphylococci spp., which were found in 19 cases: 14 (24.1%) patients had methicillin-sensitive Staphylococcus aureus, four (6.9%) patients had coagulase-negative Staphylococci and one (1.7%) patient had methicillin-resistant S. aureus (MRSA). There were six (8.6%) cases of Enterococcus faecalis, two cases of E. coli, and two cases of Pseudomonas aeruginosa. In addition, Klebsialla pnemoniae, Bacteroides and Enterobacter were isolated in one patient each. Three patients presented the following combinations of two organisms: E. coli and Bacteroides, Streptococcus pneumoniae and coagulase-negative Staphylococci, and methicillin-sensitive Staphylococci and Streptococcus agalactiae. Eleven (19%) patients had negative blood cultures, and 10 of these patients had received antibiotics before blood collection.
Management and outcomes All of the patients received at least two intravenous antibiotics. The choice of antimicrobial agents was made on the basis of the culture results. Empirical antimicrobial therapy was used for culture-negative IE. The median duration of the antimicrobial therapy was 35 days (interquartile range 23—42 days). The patients who died were on antimicrobial therapy for 16 days with an IQR of 5—26 days, and the survivors were on antimicrobial therapy for a mean of 42 days with an IQR of 30—42 days. Surgery was performed in 15 (25.9%) patients, 10 of whom had prosthetic valves and five of whom had native valves. The most commonly encountered indications for surgery were heart failure (14 patients), large (>10 mm) mobile vegetations (4 patients), and valve dehiscence and root abscess (4 patients). Other indications for surgery included prosthetic-valve IE (1 patient), septic emboli to the lungs (1 patient), and the removal of a pacemaker (1 patient). Thirty-four patients exhibited complete recovery and were discharged from the hospital without any complications. Twenty-five (43%) patients had complications related to IE: 14 patients had heart failure, three patients had embolic phenomenon, and eight patients developed CVA. The in-hospital mortality rate was 27.6% (16 patients; 11 males and five females), and the mean age of the patients who died was 51.3 years.
Discussion There is a paucity of published data of infective endocarditis in Oman. The epidemiology of
Please cite this article in press as: Al Abri SS, et al. The epidemiology and outcomes of infective endocarditis in a tertiary care hospital in Oman. J Infect Public Health (2014), http://dx.doi.org/10.1016/j.jiph.2014.04.004
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Table 3 Microorganisms obtained from culture. MSSA: methicillin-sensitive Staphylococcus aureus; MRSA: methicillin-resistant Staphylococcus aureus; CNS: coagulase-negative Staphylococcus ssp. Organism
Native valves (N = 49)
Streptococci Staphylococci MSSA MRSA CNS Enterococci Pseudomonas aeruginosa E. coli Klebsiella pneumonia Bacteroides Enterobacter Negative culture Total number of cultures
17 (34.7%)
3 (33.3%)
20 (34.5%)
11(22.5%) 1 (2%) 4 (8.2%) 4 (8.2%) 2 (4.1%) 2 (4.1%) 1 (2%) 1 (2%) 1 (2%) 10 (20.4%) 54
3 (33.3%) 0 (0%) 2 (22.2%) 1 (11.1%) 0 0 0 0 0 1 (11.1%) 10
14 (24.1%) 1 (1.7%) 6 (10.3%) 5 (8.6%) 2 (3.4%) 2 (3.4%) 1 (1.7%) 1 (1.7%) 1 (1.7%) 11 (19%) 64
IE has shown some changes in the last 30 years [1,13]. The male-to-female ratio in our study is 2.2, which is in agreement with other published studies [14,15]. The mean age of the patients in our study is 43.6 years. This age group is older than the age groups from studies published in Saudi Arabia, Kuwait, India and Tunisia, which had mean ages between 28 and 32 years [10,14,16—18]. Other studies from Europe and the United States showed that 50% or more of the IE cases occurred in patients over the age of 50 years [5,14,19,20], and these studies have shown a steady increase in the median age. The mean age of the patients in a recent study from Saudi Arabia was 59.7 years [11]. In contrast, another recent study from Saudi Arabia showed a markedly lower mean age of 30 years [14]. This trend in developed countries is likely due to two factors: the increasing proportion of elderly people in the general population and the decline in the incidence of rheumatic heart diseases as a risk factor. Rheumatic heart disease and congenital heart diseases continue to be the most important causes of IE in the Middle East [10,13,15,21,22]. However, the most predisposing valvular conditions in our study were the presence of degenerative valve disease and prosthetic valves. Our findings reveal that IE is no longer a subacute or chronic condition: most of the patients’ symptoms were present for less than three weeks before the diagnosis of IE was made. Other published studies have report a more prolonged duration of symptoms before presentation [4,23]. Fever was the most prevalent symptom, occurring in 89.7% of the patients, similarly to the findings of other studies [14,15,24].
Prosthetic valves (N = 9)
Total (N = 58)
Most cases of IE involved native valves, and the mitral valve was the most commonly affected (56.9%), although the aortic valve was involved in 39.7% of the cases. These findings are similar to the results from two studies from Saudi Arabia [10,11]. However, some recently published studies have shown that the aortic valve has replaced the mitral valve as the most commonly infected site in IE [17,23,25]. Echocardiography was the mainstay of diagnosis in our patients. The sensitivity of TTE in this study was 89.1%, which is higher than the reported range of 50—75% from other studies [10]. TEE detected vegetations in six patients who were TTE-negative. The prevalence of Staphylococci spp. was equal to the prevalence of Streptococci spp. as a cause of IE, similarly to the results from recent studies from Turkey and Tunisia [15,18]. Recent studies have shown that Staphylococci spp. have overtaken Streptococci organisms as the most frequent causes of native-valve IE [5,10,11,14,24,26]. However, studies from Kuwait, Lebanon and Pakistan [21,22,27] showed a predominance of Streptococci spp. This difference is related to the time of the study because our study was performed at a more recent date. MRSA was isolated from only one patient, and other studies from Middle Eastern countries have shown similarly low rates, ranging from 3.7 to 7% [10,11,15,22]. This finding is much lower than the results from a study performed in the USA (14.8%) [28]. This shift is due in part to the global presence of risk factors for S. aureus-associated IE, such as healthcare contact and invasive procedures [29]. We noted a comparable proportion of subjects with culture-negative IE, similarly to studies from Saudi Arabia, Lebanon and Tunisia [10,11,18,21].
Please cite this article in press as: Al Abri SS, et al. The epidemiology and outcomes of infective endocarditis in a tertiary care hospital in Oman. J Infect Public Health (2014), http://dx.doi.org/10.1016/j.jiph.2014.04.004
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S.S. Al Abri et al.
Surgical intervention was performed in 25.9% of the cases, and this surgical rate is much lower than the 44.7% surgical rate reported from Saudi Arabia, the 50% surgical rate from Tunisia, and the 48.2% surgical rate reported by the International Collaboration on Endocarditis Prospective cohort study [10,14,16]. The high rate of surgical intervention indicates that the threshold for early surgical treatment is lower than before [14]. It has been shown that early surgery may be critical in improving survival in patients with definite IE [30—32]. Our data indicate that 43% of the patients experienced complications. All of the complications described in our study have been previously reported in the literature [14]. The in-hospital mortality in our study was 27.6%, which is within the mortality rate range of 15—30% reported in other case series [14,17,19]. There was no correlation between Staphylococci spp. IE and mortality in our study, even though some studies have shown an increased mortality rate, up to 40%, in patients infected with Staphylococci spp. IE [5,14]. We may have failed to identify other important prognostic factors because of the relatively small number of cases and the retrospective nature of the study. The prolonged duration of hospitalization in our cases, similar to that reported in other studies, denotes an important cost burden and a need for home or outpatient-based management whenever appropriate [33]. Our study has several limitations: it is retrospective and uncontrolled in design, and it is based on the discharge diagnosis. Serology and polymerase chain reaction tests for fastidious organisms, such as Brucella, Bartonella, Coxiella, and other rare causes of endocarditis were not performed. In addition, the Royal Hospital is a tertiary referral center, and our data may not truly represent endocarditis in the general community and may be skewed toward a more sick patient population. The study indicates the need to develop a national or regional IE registry throughout the Middle East. In conclusion, this study describes the clinical features, complications and management of IE. Native-valve IE is the predominant type of endocarditis and is more of an acute disease. The prevalence of Staphylococci spp. IE is similar to the prevalence of Streptococci spp. IE, and the IE morbidity and mortality rates remain high.
Conflict of interest Funding: No funding sources.
Competing interests: None declared. Ethical approval: Not required.
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