Brucella endocarditis: epidemiology and clinical features of 23 cases from 2007 to 2018

Background : The data of Brucella endocarditis is relatively little. This study was to summarize the characteristics of epidemiology and clinical features of brucella endocarditis. Methods: 23 patients with brucella endocarditis collected in our hospital from July 2007 to August 2018 were analyzed. Results: Among the patients, 91.3% was male, the age was 42.6±12.4 years old. 69.6% patients had contacted with cattle and sheep. The most common symptom in these patients was chest tightness (60.8%), shortness of breath (60.8%), fever (43.5%) and anemia (43.5%). In the patients with anemia, 50% also had a lower platelet (including one patient had lower leucocyte level). Blood culture before taking antibiotics is easy to find Brucella sp . The aortic valve (91.3%) is most commonly involved, followed by mitral valve (17.4%) and tricuspid valve (8.7%). 87.0% of patients followed with complications, including cardiac failure (73.9%), pulmonary infection (43.5%), hydropericardium (34.8%), renal insufficiency (21.7%), multiple organ disfunction (4.3%), bacterial aneurysm rupture (4.3%), paravertebral abscess (4.3%), cerebral infarction (4.3%), pericardial stenosis and adhesion (4.3%). 47.8% of patients exhibited hyperglobulinemia and 80% of patients with renal insufficiency had hyperglobulinemia. 22 patients had suffered antibiotics and surgery treatment and one patient gave up treatment. 2 patients (8.7%) died because of ventricular fibrillation and refractory heart failure. Conclusion: Brucella endocarditis was a complex disease and could lead to multiple organ disfunction. Cardiac failure was the main reason for death and the mortality was 8.7%.

Background : The data of Brucella endocarditis is relatively little. This study was to summarize the characteristics of epidemiology and clinical features of brucella endocarditis. Methods: 23 patients with brucella endocarditis collected in our hospital from July 2007 to August 2018 were analyzed.

Background
Infective endocarditis (IE) is a high fatality rate of disease, the incidence of each year for 3-9/100000 cases [1][2][3][4]. Gram-positive bacteria were the main etiology of IE [5], while Brucella sp. (gram-negative bacteria) is rare. Previous studies about brucella endocarditis were mainly cases report [6][7][8]. These studies due to the limitation of the number of cases, unable to obtain some important disease information, such as common complications, mortality and the leading cause of death. Therefore, we collected 23 cases of brucella endocarditis to be analyzed in our hospital from July 2007 to August 2018.

Methods
Diagnosis of brucella endocarditis was made with history, clinical findings, echocardiographic images confirming the diagnosis of infective endocarditis, positive agglutination test [9]. Infective endocarditis was defined according to the modified Duke criteria [10].

Clinical manifestation and complications
Among 23 patients, 21 (91.3%) was male, the age was 42.6±12.4 years old, the hospital stay was 20 (9,27) days. 16 patients had contacted with cattle and sheep, while the other did not find the direct causes. Blood culture and agglutination test had been performed in all the patients, 6 cases (26.1%) found Brucella sp. using blood culture and 18 cases (78.2%) showed a higher serum brucella IgG degrees (> 1:160), only one showed positive of both. The waveform temperature change of 3 patients were showed in the figure 1 before using antibiotics. Blood culture before taking antibiotics found Brucella sp. in the 3 patients. The most common symptom in these patients was chest tightness (14 cases; 60.8%), shortness of breath (14 cases; 60.8%), fever (10 cases; 43.5%) and anemia (10 cases; 43.5%), followed by heart murmur (6 cases; 26.1%), the whole body dropsy (4 cases; 17.4%), double leg edemas (2 cases; 8.7%), splenomegaly (1 cases; 4.3%). In the patients with anemia, 5 also had a lower platelet (including 1 had lower leucocyte level). Total 20 (87.0%) patients followed with complications including cardiac failure, pulmonary infection, hydropericardium, renal insufficiency, multiple organ disfunction, bacterial aneurysm rupture, paravertebral abscess, cerebral infarction, pericardial stenosis and adhesion. The results were showed in the table 1.

Laboratory tests and Cardiac ultrasound
Among these patients, 10 cases exhibited increased erythrocyte sedimentation rate (only 13 patients

Treatment
22 patients had suffered antibiotics and surgery treatment and one patient gave up treatment. 11 patents had suffered antibiotics plus surgery treatment. Treatment data showed in the table 3. 20 patients (87.0%), had improved symptoms after treatment, were released and continued to take antibiotics for at least three months. Two of patients (both involved aortic valve) treated with Quinolone + penicillin died after 3 and 16 days , treatment, respectively. The direct cause of death were ventricular fibrillation and refractory heart failure, respectively. Cardiac failure (IV level) was the only complication in both of the death.

Discussion
The lack of abundant information about brucella endocarditis lead us to collecte the materials of the 23 patients with brucella endocarditis in our hospital from July 2007 to August 2018. These data showed that 91.3% of patients was male, the age was 42.6±12.4 years old. The most common symptom in these patients was chest tightness, shortness of breath, fever and anemia. 43.5% of patients had anemia and 47.8% exhibited hyperglobulinemia. Blood culture before using antibiotics was easier to find Brucella sp. The aortic valve is most commonly involved, followed by mitral valve and tricuspid valve. The common complications were cardiac failure, pulmonary infection, hydropericardium, renal insufficiency. 2 patients died because of ventricular fibrillation and refractory heart failure. Cardiac failure (IV level) was the main reason for death.
Brucella endocarditis seemed to be more inclined to male. Previous studies and our data all showed that above 70% of patients was male [11][12]. A review reporting brucella endocarditis (1966 to 2011) also showed 75.3% of patients were male after analyzing all English and French articles in PubMed, Google and Scopus [13]. The reason for it is still unclear. Interestingly, the research about IE also showed a higher rate of male (69.4%) [14]. Research showed that male gender contributes to the progression of aortic regurgitation [15]. The high rate of endocarditis may due to high rate of damage and degeneration of valve in male.
Isolation of Brucella sp. in the blood is important for the diagnosis of brucella endocarditis. However, the positive rate was low in brucella endocarditis. The reason for the low rate may be the using of antibiotics. Our results showed that only 26.1% of patients found Brucella sp. in the blood. While blood culture performed before using antibiotics all found Brucella sp. The results indicated that it was important to perform blood culture before using antibiotics to find Brucella sp.
Koruk ST, et al showed involvement rates of the aortic, mitral and tricuspid valves were 49.1%, 43.4% and 5.7% in Brucella endocarditis, respectively [16]. Our results showed that Brucella mainly infected aortic valve (91.3%), followed by mitral (17.4%) and tricuspid valve (8.7%). The retrospective research about infection endocarditis cases also showed a higher rate of left native valve [14]. Left native valve seemed to be easier to be involved. A possible reason may be a higher pressure in left ventricle, and thus more susceptible to be damaged than other heart valves. Our results also showed that 21.7% of patients with Brucella endocarditis were congenital bicuspid aortic valve. Congenital valvular disorder made Brucella sp. easier to settle down in the damage valves.
Hyperglobulinemia was found in 47.8% of patients. Interestingly, 4 of 5 patients with renal insufficiency also exhibited hyperglobulinemia. As we known that immunoglobulin deposition is a important reason leading to chronic kidney disease [17]. Thus, the complication of renal insufficiency may due to hyperglobulinemia. The infections generally induce the formation of immune complexes, and glomerulonephritis occurs after the deposition of immune complexes in the kidney. A case report about Brucella glomerulonephritis showed that glomerulonephritis could be managed by only using antibiotic therapy, supporting our hypothesis [18]. The results also indicated that antibiotics treatment was also important to control the complication.
Antibiotics with or without surgery treatment was the main treatment for the Brucella endocarditis.
Our results showed that Rifampin +tetracycline was an effective treatment for Brucella endocarditis.
Keshtkar-Jahromi M, et al showed that the mortality of Brucella endocarditis was 32.7% in the only medical treatment patients, 6.7% in the combined medical and surgical treatment and total mortality was 10.7% from 1966 to 2011 [13]. While, our recent data showed the mortality in the only medical treatment patients was 18.2%, no death in combined surgical and medical therapy and the total mortality was 8.7%. Research about showed 50% of death occurred during or early after surgery mostly related to cardiac arrhythmias in Brucella endocarditis from 1991 to 2009 [11]. A more experiential heart valve replacement surgery may lead to low death in patients with combined medical and surgical treatment in our results. Two patients treated with quinolone + penicillin died because of cardiac failure in a short time after admission. Quinolone + penicillin was used because of delayed diagnosis of Brucella endocarditis. These results indicated effective antibiotics application was important to control the progression of Brucella endocarditis. Cardiac failure (IV level) was main reason for death. Koruk ST, et al showed that mortality increased 25-fold after complication with congestive heart failure, supporting our results [16].

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Competing Interest
None to declare for all the authors.

Funding
XL has received grants (2010DS890294) from the Open Topics of Xinjiang Key Laboratory of critical Disease though " T cell subgroup analysis in Brucella patients" (SKLIB-XJMDR-2014-2).

Authorship contributions
LZ and XL designed the research, collected and analyzed data, and wrote the paper. TZ and JY contributed to data acquisition. DH and RG contributed to analysis of data. All authors had read and approved the Manuscript    Figure 1 The waveform temperature change of 3 patients whose blood culture was performed before using antibiotic.