Clinical characteristics and outcome of Brucella endocarditis

Introduction

Brucellosis is a zoonosis with a worldwide distribution, especially in the Mediterranean Basin, the Arabian Peninsula, the Indian Subcontinent, Mexico and Central and South America. ¹ It is a systemic disease, and almost every organ can be affected. Cardiovascular complications, which include endocarditis, myocarditis and pericarditis, occur in less than 2% of patients with brucellosis. ² Brucella endocarditis, although a rare complication of brucellosis, is the main cause of death from this disease. We report our experience with six cases of Brucella endocarditis.

Patients and methods

After a retrospective search we found six cases diagnosed as Brucella endocarditis between May 2003 and October 2007 at the Departments of Infectious Diseases, Cardiology and Cardiovascular Surgery, Yuzuncu Yil University Research Hospital, Van, Turkey. Endocarditis was established in the presence of endocarditis findings associated with either Brucella spp. positive blood cultures or a standard agglutination test (SAT) titre of ≥1/160. The agglutination test was performed using a commercial kit (Cromatest, Knickerbacker Laboratories, Barcelona, Spain).

Follow-up data of patients were obtained via telephone questionnaires and/or from hospital examinations. A transthoracic echocardiography was performed on all patients. Transesophageal echocardiography (TEE) was performed in the suspicion of infective endocarditis if transthoracic echocardiography was unable to demonstrate vegetation. Antibiotherapy was continued for at least two months. The end-point of antibiotic therapy was the normalization of clinical and laboratory condition (decrease in erythrocyte sedimentation rate [ESR]and C-reactive protein [CRP] levels, echocardiographic findings, decrease or stabilization of SAT titres, etc.).

Results

The age of the patients ranged between 18 and 53 years. Five of the six patients were male. One patient had undergone aortic and mitral mechanic valve prosthesis replacement (aortic valve replacement [AVR] +mitral valve replacement [MVR]) 6 years ago. Other patients did not have a previous history of cardiovascular disease. All patients complained of fever. Other symptoms included sweating, chills, dyspnea, weight loss and arthralgia (Table 1). One patient had left-sided hemianopsia. The duration of symptoms ranged between one week and eight months. All patients had been given a different type of antibiotherapies in other primary health-care units before blood cultures were taken (for seven to 15 days duration).

None of the patients had congestive heart failure or left ventricular systolic function on echocardiography. Four patients had valvular disease, one had AVR + MVR and one had secundum type atrial septal defect (ASD). Although transthoracic echocardiography demonstrated normal functioning mechanic valves, blood culture and agglutination tests were positive in the patient with AVR + MVR who refused TEE. Vegetations showed in the TEE of four patients. Blood culture grew Brucella mellitensis only in two patients. Standard agglutination tests were elevated in all patients (range 1/320–1/10240). The ESR was elevated in four (45 to 60 mm/h) and CRP in all patients (range 11 to 220 mg/L) (Table 2). Three patients had haematocrit levels of <30% and four had a leukocyte count of >10,000/mm³. One patient presented with left-sided haemianopsia had retinal septic emboli on fundus floresein angiography.

Two patients died during follow-up. One who had a previous AVR + MVR operation refused further treatment and died one month later. The other patient was treated for brucellosis for one month and required haemodialysis due to acute renal failure when an infective endocarditis was diagnosed. Rifampicin was suspected to have caused acute renal failure but the renal biopsy revealed findings consistent with chronic renal failure. Due to an inadequate response to antibrucellar therapy and a suspicion of coexistent microorganisms for endocarditis, ceftriaxone and vancomycin were added to the treatment. The patient underwent cardiovascular surgery. Follow-up was lost for one patient with severe aortic regurgitation who had refused an operation. Therefore of the five patients with known follow-up, three were managed with combined medical and surgical therapy successfully. Exitus occurred in one patient treated with combined medical and surgical therapy and in one patient given medical therapy alone.

Discussion

Brucellosis is a zoonosis that can affect multiple organ systems, and endocarditis is the most destructive, therapy-resistant and with fatal complications, although Brucella endocarditis is very rare it may reach up to 10.9% in endemic regions. ³ The endocarditis rate has been reported as 0.7% from Turkey. ⁴ Brucellosis is endemic in eastern Turkey, especially in our area, due to the consumption of unpasteurized or unboiled dairy products.

Published reports indicate that Brucella endocarditis usually involves normal native valves, and predominantly the aortic valve in 75% of cases. ² Four of our patients had aortic valve involvement, two of whom had coexistent mitral valve involvement. One patient had prosthetic valve endocarditis and one had vegetation on ASD. Brucella prosthetic valve endocarditis is a very rare disease. ^5,6 An ASD presenting with endocarditis in an adult is extremely rare. Successful treatment of ASD Brucella endocarditis with combined surgical and medical treatment has been reported. ⁷

Blood cultures were positive only in two patients. Blood cultures, although highly specific, present a quite low sensitivity (15-20%). ⁸ Due to the slow growth rate of Brucella spp. and their fastidiousness Brucella endocarditis is often a culture-negative endocarditis and in many series it forms part of the pool of cases of pathogen-induced endocarditis with negative blood cultures. ⁹ This low yield of positive blood cultures may be also due to previous antibiotic treatment and a long interval between the onset of symptoms and the final diagnosis. ^6,10 Serologic tests, although more sensitive, are not wholly specific, may be difficult to interpret in endemic areas and may be negative during early stages of the disease. ¹¹ However, due to the fulminant course of the disease, treatment should be initiated on the grounds of high clinical suspicion and should not be delayed until culture results are known. ^2,3

Uncertainty exists regarding many aspects of the treatment of Brucella endocarditis, including the appropriate antibiotic combination and its duration, and the indications for surgery and its timing. ^1–6,12,13 A combination of antimicrobial agents and valve replacement is the most accepted treatment. ^3,12–14 Antimicrobial agents can achieve sterilization of valve vegetations, and several cases of successful cures of native valve Brucella endocarditis with medical therapy alone have been reported. ^4,15 Antibiotic treatment alone has been suggested as an alternative in patients without prosthetic valves, heart failure, abscess formation or valvular destruction. ⁴ Medical therapy consists of a combination of antibiotics used over a long period. The optimal combination and duration are unknown. In different reports, the duration of antibiotic therapy ranged from six weeks to 12 months. The decision to stop treatment must be determined in each case after thorough clinical observation. In our patients antibiotherapy was terminated depending on clinical, laboratory and echocardiographic findings. Combined therapy with surgery was successful in three of four patients. However, the clinical condition of the patient who died was worse and surgery should not be blamed for the failure in that case. The outcome of antibiotherapy alone cannot be extracted in the present series, as one patient refused further treatment and follow-up was lost for the other.

In conclusion, Brucella endocarditis although rare, should be suspected in the areas where brucellosis is endemic. Due to the fulminant course of the disease, treatment should be initiated on the grounds of a high clinical suspicion, even if the culture results are unknown or negative. Agglutination titres aid the diagnosis. A combination of antibiotherapy and surgery seems to be preferable treatment modality.