Brucella endocarditis as a late onset complication of brucellosis.

Brucella endocarditis (BE) is a rare but life threatening complication of brucellosis. We present a case report of a patient with relapsing brucellosis complicated with aortic valve endocarditis. The patient underwent valve replacement and required prolonged antibiotic treatment because of rupture of the noncoronary leaflet and development of congestive heart failure. Since the onset of endocarditis in patients with brucellosis is not known, proper follow-up is required in order to identify any late onset complications, especially in endemic areas.


Introduction
Brucella infection can affect different organs and systems and the disease course may be complicated by severe and/or rare life threatening clinical entities such as neurobrucellosis and endocarditis [1][2][3]. Brucella endocarditis (BE) is one of the most challenging localizations of the disease, requiring prompt diagnosis and constant evaluation of the treatment plan in order to assess whether the patient will require surgical repair of the infected valve or continue with medical treatment alone [4][5][6]. However, little is known about the onset of endocarditis and possible measures to avoid this potentially fatal complication. Herein, we present a patient with relapsing Brucella infection complicated by Brucella endocarditis and we review the literature in order to clarify the specific characteristics of BE compared to other infectious causes of endocarditis.

Case Presentation
A 50-year-old male livestock farmer was admitted to Sparta General Hospital with a 4-day history of fever, malaise, night sweats, and shortness of breath. He had been diagnosed with blood culture proven Brucella infection 6 months ago and was treated with a double regimen of 21 days of streptomycin and two months of doxycycline. He had recovered completely and Brucella antibodies titers were negative after two months of treatment. On admission, he was febrile (38.7 ∘ C) and physical examination revealed cervical lymphadenopathy, hepatosplenomegaly, and a 2/6 diastolic aortic murmur not reported in his previous medical history. According to CBC he was anemic (Ht 24%) and leukopenic (3.200/ L), ESR was 102 mm/h, and biochemistry revealed a serum creatinine value of 2.1 mg/dL while BUN levels were 92 mg/dL. Wright standard tube agglutination test was positive in a titer of 1 : 1600. Blood cultures were positive for Brucella spp. that was identified later as melitensis. In transthoracic echocardiogram, vegetations were present on a bicuspid aortic valve (Figure 1). A triple antibiotic regimen with 900 mg of rifampicin, 200 mg of doxycycline daily, and streptomycin adjusted for renal failure was initiated. Transesophageal echocardiogram was performed the next day and confirmed the presence of active vegetations but also revealed severe aortic regurgitation and rupture of the noncoronary leaflet. He was referred for cardiothoracic consultation and a valve replacement surgery was decided. During hospitalization, fever, malaise, and renal failure had gradually resolved, but he developed decompensated heart failure requiring loop diuretics and oxygen supplementation. On the 21st day of treatment, streptomycin has been replaced with cotrimoxazole and three days later valve replacement was performed. The patient recovered without any surgical complications, continued antibiotic treatment for 6 months, and is currently well.

Discussion
Endocarditis is a well-documented complication of Brucella as far as clinical presentation and treatment options are concerned, accounting for the majority of fatal cases. A combined search of PubMed and Google Scholar for the terms "Brucella" and "endocarditis" in the title of the article returns 166 results, from as early as 1936. In two of the earliest reports Quintin and Stalker [7] and Hart et al. [8] describe the fatal outcome of Brucella abortus endocarditis. Aortic valve is the valve predominantly affected in Brucella endocarditis and mitral involvement is usually seen in preexisting rheumatic disease; preexisting valvular disease usually accounts for less than half of the reported cases in total [4,9]. However healthy valves, as in this case report, also are often affected. Vegetations of the leaflets are the most common finding; however ulcerations, abscesses, and rupture of leaflets have been described [10,11]. Congestive heart failure is the complication that may require emergency cardiac surgery. Keshtkar-Jahromi et al. [12] in a retrospective study of 308 cases assessed the role of surgery to the treatment and concluded that surgery reduced mortality of Brucella endocarditis from 32.7% in medical treatment alone to 6.7% in combined medical and surgical strategies ( < 0.001); similar results were reported in a study of 53 patients in Turkey [13].
Brucella is considered a rare endocarditis pathogen and is usually classified in culture negative endocarditis in review articles because Brucella spp. do not grow in usually used culture systems [14,15]. However, the use of automated culture systems has reduced dramatically the time needed for identification of Brucella [16] and the term "culture negative" is not appropriate, since most reports have identified the pathogen in blood cultures [12,13].
Whether BE is an acute infection or a result of chronic or relapsing Brucella infection is not clear. Recent reports on acute infectious endocarditis, using modern microbiology techniques, do not mention Brucella as a common pathogen [17,18] but they come from nonendemic areas. In case series from endemic areas, patient history is often too vague to clarify whether endocarditis is an acute or late onset complication of the systemic infection [10,12,13,19,20].
In conclusion, we present a patient with late onset Brucella endocarditis that destroyed the noncoronary leaflet of his bicuspid aortic valve, requiring the combination of valve replacement and prolonged antibiotic treatment. The patient had a relapse of a previously successfully treated uncomplicated Brucella infection; this case report prompts the need of a proper follow-up of every Brucella infected patient after the initial diagnosis, since relapses may involve organs not affected in the first infection, especially in endemic areas and in individuals with professional exposure to risk factors for brucellosis.